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Lee I, Agrawal A, Ghandour S, Suarez S, Patel S, Young E, Hagos F, Yeng T, Hall R, Hansraj N, Rodriguez A, Zacharias N, Dua A. The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease. Ann Vasc Surg 2025; 110:246-259. [PMID: 39067844 DOI: 10.1016/j.avsg.2024.06.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/06/2024] [Accepted: 06/02/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Elevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis postrevascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. METHODS Patients with peripheral artery disease undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, postoperative day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student's t-test for pairwise analysis and Mann-Whitney U tests. RESULTS Among 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, P < 0.01), AA MA (36.6 vs. 29.65, P < 0.05), clot strength without platelets activator F MA (13.10 vs. 10.80, P < 0.01), and heparin-neutralized uninhibited clot strength from thrombin activation heparinized kaolin with heparinase MA (61.10 vs. 57.70, P < 0.01) values at baseline. Postoperatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen citrated functional fibrinogen levels (40.95 vs. 371.35, P < 0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor citrated functional fibrinogen MA values (22.90 vs. 20.40, P < 0.05) when measured within 36 hrs of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261-unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. CONCLUSIONS Elevated HbA1c levels appear to be associated with prothrombotic tendencies in clot dynamics as measured by thromboelastography with platelet mapping, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.
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Affiliation(s)
- Ivy Lee
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Aniket Agrawal
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Samir Ghandour
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Sasha Suarez
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Shiv Patel
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Elizabeth Young
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Fanah Hagos
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Tina Yeng
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Ryan Hall
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Natasha Hansraj
- Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, Houston, TX
| | - Adriana Rodriguez
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Nikolaos Zacharias
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA
| | - Anahita Dua
- Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA.
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Schneider DJ, Taatjes-Sommer HS, DiBattiste PM, Palla KS, Shovah T, Biswas S, Ohrnberger J. Assessing prognosis by quantifying FcγRIIa on fixed platelets. Bioanalysis 2024; 16:1025-1032. [PMID: 39229648 PMCID: PMC11581188 DOI: 10.1080/17576180.2024.2395706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/20/2024] [Indexed: 09/05/2024] Open
Abstract
Introduction: FcγRIIa amplifies platelet activation and higher platelet FcγRIIa identifies patients at greater risk of subsequent cardiovascular events. We report the accuracy and precision of a modified test to quantify FcγRIIa on previously fixed platelets (pFCG test).Methods & results: An antibody clone (5G1) was developed after exposure of mice to formaldehyde treated FcγRIIa. Accuracy and precision of the modified test was evaluated with biologic specimens (platelets) and engineered synthetic cells conjugated with FcγRIIa (Slingshot Biosciences). The modified pFCG test on fixed platelets (using 5G1) consistently identified modestly more (∼300 molecules) of FcγRIIa on platelets compared with the pFCG test on nonfixed platelets (using clone FL18.26). With biologic specimens, the intra-assay coefficient of variation (CV) was 2.1 ± 0.1% (standard error of the mean, n = 750). The interassay CV was assessed intraday (4.5 ± 1%) and interday (up to 5 days after fixation, 6.5 ± 0.4%, n = 50). The pFCG test performed on Slingshot Synthetic cells conjugated with FcγRIIa demonstrated accuracy, linearity (R2 = 0.984) and similar interassay CV both intraday (2% ± 0.6%) and interday (20 nonconsecutive days, 9.9% ± 2.1%).Conclusion: In summary, modification of the pFCG test to be performed on fixed platelets allows accurate quantification of pFCG with high precision.
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Affiliation(s)
- David J Schneider
- Department of Medicine, Cardiovascular Research Institute, The University of Vermont, Burlington, VT, 05401, USA
| | - Heidi S Taatjes-Sommer
- Department of Medicine, Cardiovascular Research Institute, The University of Vermont, Burlington, VT, 05401, USA
| | | | | | - Tyler Shovah
- Slingshot Biosciences Inc, Emeryville, CA, 94608, USA
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Fioretti V, Sperandeo L, Gerardi D, Di Fazio A, Stabile E. Antiplatelet Therapy for Elderly Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. J Clin Med 2024; 13:4229. [PMID: 39064269 PMCID: PMC11277659 DOI: 10.3390/jcm13144229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 07/08/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
The elderly represent an increasing proportion of patients presenting with acute coronary syndrome (ACS). Various data have shown that the benefits of percutaneous coronary revascularization are maintained in elderly patients presenting with ACS. Conversely, the management of antiplatelet therapy remains challenging and controversial, because older patients are usually at a high risk of both ischemia and bleeding. Moreover, the recommended ischemic and bleeding risk scores in patients with ACS were developed from studies with a low representation of older patients. New antiplatelet strategies have been developed, but their evidence in elderly patients is limited because they are usually underrepresented in randomized clinical trials due to their clinical complexity. The aim of this review is to summarize the different factors associated with increased ischemic and/or bleeding risk and the scientific evidence about the different antiplatelet strategies in elderly patients presenting with ACS and undergoing percutaneous coronary revascularization.
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Affiliation(s)
- Vincenzo Fioretti
- Division of Cardiology, Cardiovascular Department, Azienda Ospedaliera Regionale “San Carlo”, 85100 Potenza, Italy
- Department of Advanced Biomedical Sciences, Federico II University of Naples, 80131 Naples, Italy
| | - Luca Sperandeo
- Department of Advanced Biomedical Sciences, Federico II University of Naples, 80131 Naples, Italy
| | - Donato Gerardi
- Division of Cardiology, Cardiovascular Department, Azienda Ospedaliera Regionale “San Carlo”, 85100 Potenza, Italy
| | - Aldo Di Fazio
- Regional Complex Intercompany Institute of Legal Medicine, Azienda Ospedaliera Regionale ”San Carlo”, 85100 Potenza, Italy;
| | - Eugenio Stabile
- Division of Cardiology, Cardiovascular Department, Azienda Ospedaliera Regionale “San Carlo”, 85100 Potenza, Italy
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Won KB, Kim HJ, Cho JH, Lee SY, Her AY, Kim BK, Joo HJ, Park Y, Chang K, Song YB, Ahn SG, Suh JW, Cho JR, Kim HS, Kim MH, Lim DS, Kim SW, Jeong YH, Shin ES. Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction. Sci Rep 2024; 14:10894. [PMID: 38740817 DOI: 10.1038/s41598-024-60999-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/30/2024] [Indexed: 05/16/2024] Open
Abstract
This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.
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Affiliation(s)
- Ki-Bum Won
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
| | - Hyeon Jeong Kim
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
- Division of Cardiology, Busan Veterance Hospital, Busan, South Korea
| | - Jun Hwan Cho
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
| | - Sang Yup Lee
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
| | - Ae-Young Her
- Division of Cardiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Byeong-Keuk Kim
- Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyung Joon Joo
- Division of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Yongwhi Park
- Division of Cardiology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, South Korea
| | - Kiyuk Chang
- Division of Cardiology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Young Bin Song
- Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung Gyun Ahn
- Division of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea
| | - Jung-Won Suh
- Division of Cardiology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jung Rae Cho
- Division of Cardiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Hyo-Soo Kim
- Division of Cardiology, Seoul National University Hospital, Seoul, South Korea
| | - Moo Hyun Kim
- Division of Cardiology, Dong-A University Hospital, Busan, South Korea
| | - Do-Sun Lim
- Division of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Sang-Wook Kim
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
| | - Young-Hoon Jeong
- Division of Cardiology, Chung-Ang University Gwangmyeong Medical Center, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
| | - Eun-Seok Shin
- Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, South Korea.
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Cha J, Lee S, Park JH, Hong SJ, Ahn TH, Chang K, Park Y, Song YB, Ahn SG, Suh J, Lee SY, Cho JR, Her A, Jeong Y, Kim H, Kim MH, Shin E, Kim B, Lim D. Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients. J Am Heart Assoc 2024; 13:e031819. [PMID: 38639339 PMCID: PMC11179895 DOI: 10.1161/jaha.123.031819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 03/12/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. METHODS AND RESULTS The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. CONCLUSIONS HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.
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Affiliation(s)
- Jung‐Joon Cha
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
| | | | - Jae Hyoung Park
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
| | - Soon Jun Hong
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
| | - Tae Hoon Ahn
- Cardiovascular CenterChung‐Ang University Gwang‐myeong Hospital, Chung‐Ang University College of MedicineGwang‐myeongSouth Korea
| | - Kiyuk Chang
- Division of Cardiology, Department of Internal Medicine, College of MedicineCatholic University of KoreaSeoulSouth Korea
| | - Yongwhi Park
- Department of Internal MedicineGyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon HospitalChangwonSouth Korea
| | - Young Bin Song
- Division of Cardiology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
| | - Sung Gyun Ahn
- Department of CardiologyYonsei University Wonju Severance Christian HospitalWonjuSouth Korea
| | - Jung‐Won Suh
- Department of Cardiology, Seoul National University College of MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
| | - Sang Yeub Lee
- Cardiovascular CenterChung‐Ang University Gwang‐myeong Hospital, Chung‐Ang University College of MedicineGwang‐myeongSouth Korea
| | - Jung Rae Cho
- Cardiology Division, Department of Internal MedicineKangnam Sacred Heart Hospital, Hallym University College of MedicineSeoulSouth Korea
| | - Ae‐Young Her
- Division of Cardiology, Department of Internal MedicineKangwon National University School of MedicineChuncheonSouth Korea
| | - Young‐Hoon Jeong
- Cardiovascular CenterChung‐Ang University Gwang‐myeong Hospital, Chung‐Ang University College of MedicineGwang‐myeongSouth Korea
| | - Hyo‐Soo Kim
- Department of Internal Medicine and Cardiovascular CenterSeoul National University HospitalSeoulSouth Korea
| | - Moo Hyun Kim
- Department of CardiologyDong‐A University HospitalBusanSouth Korea
| | - Eun‐Seok Shin
- Division of CardiologyUlsan University Hospital, University of Ulsan College of MedicineUlsanSouth Korea
| | | | - Do‐Sun Lim
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
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Long Zhe G, Hau Yu L, Lee DH, Kim MH, Serebruany V. Adjunctive Cilostazol in Patients With High Residual Platelet Reactivity After Drug-Eluting Stent Implantation: A Randomized, Open-Label, Single-Center, Prospective Study (ADJUST-HPR). Am J Ther 2024; 31:e229-e236. [PMID: 37099013 DOI: 10.1097/mjt.0000000000000244] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/27/2023]
Abstract
BACKGROUND Cilostazol as an adjunct to dual antiplatelet therapy (DAPT) postcoronary stenting may further reduce vascular occlusion risks. The aim of this study was to assess the impact of cilostazol on high residual platelet reactivity (HRPR) in patients undergoing drug-eluting coronary stent implantation. METHODS In a randomized, open-label, single-center, prospective study, the degree of platelet inhibition by cilostazol 100 mg twice daily was assessed on top of conventional DAPT compared with standard clopidogrel and low-dose aspirin combination in poststent patients with HRPR. HRPR was defined as P2Y12 units (PRU) > 240 as measured by the VerifyNow P2Y12 assay. In addition, the platelet activity was assessed by light transmittance aggregometry (LTA) and Multiplate electrode analyzer (MEA). RESULTS The total of 148 patients were screened, and HRPR was observed in 64 (43.2%). Those were randomized for DAPT versus triple therapy (TAPT). After 30 days, TAPT group exhibited significantly lower rate of HRPR when assessed by all 3 devices (VerifyNow: 40.0 vs. 66.7% P = 0.04, LTA: 6.7 vs. 30.0% P = 0.02, MEA: 10.0 vs. 30.0% P = 0.05 L all vs. DAPT). Also, higher absolute mean difference in TAPT versus DAPT group after 30 days (VerifyNow: 71.3 ± 38.2 vs. 24.6 ± 40.2 P < 0.001, LTA: 23.9 ± 15.1 vs. 9.4 ± 11.8 P < 0.001, MEA: 9.3 ± 12.9 vs. 2.4 ± 17.3 P = 0.08) was observed. CONCLUSIONS Cilostazol in addition to standard DAPT reduces the incidence of HRPR and diminishes further platelet activity in poststent patients. Whether this favorable laboratory finding will affect clinical outcomes requires an adequately powered randomized trial.
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Affiliation(s)
- Guo Long Zhe
- Department of Cardiology, Dong-A University Hospital, Busan, Republic of Korea
- Department of Cardiology, Affiliated Qiqihar Hospital, Southern Medical University, China
| | - Long Hau Yu
- Department of Cardiology, Dong-A University Hospital, Busan, Republic of Korea
- Department of Cardiology, Guilin Medical University, China
| | - Dong-Hyun Lee
- Department of Intensive Care Medicine, Dong-A University Hospital, Busan, Republic of Korea; and
| | - Moo Hyun Kim
- Department of Cardiology, Dong-A University Hospital, Busan, Republic of Korea
| | - Victor Serebruany
- Division of Neurology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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Chang WT, Huang PS, Su LW, Liao CT, Siong Toh H, Chen YC, Chung‑Han H, Chen ZC, Hsu PC, Hong CS. Utility of the ACD-GENE-CLI Score in Asian Patients with Critical Limb Ischemia Undergoing Endovascular Interventions. J Atheroscler Thromb 2024; 31:572-586. [PMID: 38092392 PMCID: PMC11079481 DOI: 10.5551/jat.64326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 10/19/2023] [Indexed: 05/03/2024] Open
Abstract
AIMS Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel. METHODS Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes. RESULTS A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs. CONCLUSIONS The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.
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Affiliation(s)
- Wei-Ting Chang
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Po-Sen Huang
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Li-Wei Su
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chia-Te Liao
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium
| | - Han Siong Toh
- Department of Intensive Care Medicine, Chi Mei Medical Centre, Tainan, Taiwan
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Yi-Chen Chen
- Department of Medical Research, Chi-Mei Medical Center, Tainan
| | - Ho Chung‑Han
- Department of Medical Research, Chi-Mei Medical Center, Tainan
- Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Zhih-Cherng Chen
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Po-Chao Hsu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chon-Seng Hong
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
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Liu Z, Huang X, Gao X, Zhang T, He C, Ding L, Li Y. Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification. J Cardiovasc Pharmacol 2024; 83:173-182. [PMID: 38032897 DOI: 10.1097/fjc.0000000000001514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 10/24/2023] [Indexed: 12/02/2023]
Abstract
ABSTRACT As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 μM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.
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Affiliation(s)
- Zhanshu Liu
- Department of Hematology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaojing Huang
- Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; and
| | - Xuemei Gao
- Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; and
| | - Tiancong Zhang
- Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; and
| | - Cui He
- Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; and
| | - Ling Ding
- Yongchuan Sub-center, Chongqing Blood Center, Chongqing, China
| | - Yuan Li
- Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; and
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9
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Qu H, Zhang Y, Shi JH, Zhao YH, Gao J, Gao ZY, Shi DZ. Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme. Curr Med Chem 2024; 31:3844-3856. [PMID: 37226795 DOI: 10.2174/0929867330666230524142632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 03/03/2023] [Accepted: 04/14/2023] [Indexed: 05/26/2023]
Abstract
INTRODUCTION Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. RESULTS The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-- choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.
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Affiliation(s)
- Hua Qu
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
- NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Beijing, China
| | - Ying Zhang
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Jun-He Shi
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi-Han Zhao
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Gao
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Zhu-Ye Gao
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Da-Zhuo Shi
- Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
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10
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Gao H, Yang N, Yang L, Wang H, Zhang G, Ma X, Deng N. Advances and Perspectives in methods for identifying high platelet reactivity. Heliyon 2023; 9:e22214. [PMID: 38107326 PMCID: PMC10724541 DOI: 10.1016/j.heliyon.2023.e22214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 11/06/2023] [Accepted: 11/07/2023] [Indexed: 12/19/2023] Open
Abstract
Antiplatelet therapy is the foundational treatment for the prevention and treatment of coronary and cerebrovascular ischemic events in patients with coronary heart disease, ischemic stroke, and transient ischemic attack (TIA). However, with more and more studies reporting an increased risk of thrombosis in some patients due to poor response to therapeutic agents, the selection of appropriate P2Y12 inhibitors has become a major challenge that needs to be addressed urgently. Currently, commonly used oral P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel. Assessing patients' risk factors before the development of treatment regimens by effectively predicting the risk of high platelet reactivity with specific P2Y12 inhibitors in advance to avert the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) is the key point to the problem. Up to now, methods available for predicting platelet reactivity include genetic testing, platelet function testing, and risk scores. This review provides a summarization of the existent available identification methods and analyzes the advantages and drawbacks of different methods in specific clinical settings, intending to guide the rational clinical application of P2Y12 receptor inhibitors.
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Affiliation(s)
- Hua Gao
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
- School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China
| | - Nan Yang
- School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China
| | - Libo Yang
- Heart Centre and Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
| | - Hui Wang
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
| | - Guoshan Zhang
- Heart Centre and Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
| | - Xueping Ma
- Heart Centre and Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
| | - Ning Deng
- Office of Drug Clinical Trial Organization, General Hospital of Ningxia Medical University, Yinchuan, 750004, China
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11
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Gegri M, Cheves TA, Anderson MN, McTaggart R, Sweeney JD. Discordance in tests used to detect inhibition of the P2Y12 receptor in patients undergoing interventional neuroradiology procedures. Interv Neuroradiol 2023; 29:655-664. [PMID: 36039509 PMCID: PMC10680952 DOI: 10.1177/15910199221122858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Clopidogrel is an inhibitor of the P2Y12 platelet receptor but testing to demonstrate a drug effect is controversial since there are often discordant results between different tests methods. METHODS Samples from patients taking clopidogrel prior to intracranial flow-diversion procedures were tested using light transmission aggregometry (LTA), whole blood impedance aggregometry (WBIA) and the VerifyNow device (VND). Samples were classified as concordant if all test results were either responsive (inhibition) or resistant. Discordant results were separated using the VND into those with a responsive versus a resistant test result. RESULTS Samples from 96 patients were studied. Concordance for all three tests was seen in 53/96 (55%) of samples, of which 41 (43%) were responsive and 12 (12%) were resistant. Discordance was observed in 43 samples (45%), 37 (28%) of which were caused by responsive VND and either a resistant WBIA or LTA and 6 (7%) of which were caused by a resistant VND but a responsive test result using either WBIA or LTA. These two discordant groups differed in both platelet count and hematocrit, but no such difference was present between the two concordant groups. CONCLUSION Discordance in P2Y12 inhibition testing may be partly explained by sample platelet count and hematocrit.
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Affiliation(s)
- Mansour Gegri
- Departments of Coagulation and Transfusion Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Tracey A Cheves
- Departments of Coagulation and Transfusion Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Matthew N Anderson
- Departments of Neurosurgery, Warren Alpert School of Medicine at Brown University, Rhode Island Hospital, Providence, RI, USA
| | - Ryan McTaggart
- Departments of Diagnostic Imaging, Rhode Island Hospital, Providence, RI, USA
- Departments of Neurology, Rhode Island Hospital, Providence, RI, USA
- Departments of Neurosurgery, Warren Alpert School of Medicine at Brown University, Rhode Island Hospital, Providence, RI, USA
- The Norman Prince Neuroscience Institute, Rhode Island Hospital, Providence, RI, USA
| | - Joseph D Sweeney
- Departments of Coagulation and Transfusion Medicine, Rhode Island Hospital, Providence, RI, USA
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12
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Dalçóquio TF, Alves Dos Santos M, Silva Alves L, Bittar Brito Arantes F, Ferreira-Santos L, Pinto Brandão Rondon MU, Furtado RHM, Gehlen Ferrari A, Genestreti Rizzo PR, Salsoso R, Franci A, Moreira Baracioli L, de Nazare Nunes Alves MJ, Negrão CE, Nicolau JC. Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial. Platelets 2023; 34:2139821. [PMID: 36377063 DOI: 10.1080/09537104.2022.2139821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 10/20/2022] [Indexed: 11/17/2022]
Abstract
Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y12 (measured by P2Y12 reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).
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Affiliation(s)
- Talia Falcão Dalçóquio
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Mayara Alves Dos Santos
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Leandro Silva Alves
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Flávia Bittar Brito Arantes
- Hospital das Clinicas, Faculdade de Medicina, Universidade Federal de Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Larissa Ferreira-Santos
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Remo Holanda M Furtado
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Aline Gehlen Ferrari
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Paulo Roberto Genestreti Rizzo
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Rocio Salsoso
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Andre Franci
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Luciano Moreira Baracioli
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Carlos Eduardo Negrão
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - José Carlos Nicolau
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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13
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Chen L, Yu L, Chen M, Liu Y, Xu H, Wang F, Zhu J, Tian P, Yi K, Zhang Q, Xiao H, Duan Y, Li W, Ma L, Zhou F, Cheng Y, Bai L, Wang F, Xiao X, Zhu Y, Yang Y. A microfluidic hemostatic diagnostics platform: Harnessing coagulation-induced adaptive-bubble behavioral perception. Cell Rep Med 2023; 4:101252. [PMID: 37879336 PMCID: PMC10694630 DOI: 10.1016/j.xcrm.2023.101252] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 05/10/2023] [Accepted: 09/29/2023] [Indexed: 10/27/2023]
Abstract
Clinical viscoelastic hemostatic assays, which have been used for decades, rely on measuring biomechanical responses to physical stimuli but face challenges related to high device and test cost, limited portability, and limited scalability.. Here, we report a differential pattern using self-induced adaptive-bubble behavioral perception to refresh it. The adaptive behaviors of bubble deformation during coagulation precisely describe the transformation of viscoelastic hemostatic properties, being free of the precise and complex physical devices. And the integrated bubble array chip allows microassays and enables multi-bubble tests with good reproducibility. Recognition of the developed bubble behaviors empowers automated and user-friendly diagnosis. In a prospective clinical study (clinical model development [n = 273]; clinical assay [n = 44]), we show that the diagnostic accuracies were 99.1% for key viscoelastic hemostatic assay indicators (reaction time [R], kinetics time [K], alpha angle [Angle], maximum amplitude [MA], lysis at 30 min [LY30]; n = 220) and 100% (n = 44) for hypercoagulation, healthy, and hypocoagulation diagnoses. This should provide fresh insight into existing paradigms and help more clinical needs.
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Affiliation(s)
- Longfei Chen
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China; Shenzhen Research Institute, Wuhan University, Shenzhen 518000, China
| | - Le Yu
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China; Shenzhen Research Institute, Wuhan University, Shenzhen 518000, China
| | - Ming Chen
- Department of Blood Transfusion, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Yantong Liu
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China; Shenzhen Research Institute, Wuhan University, Shenzhen 518000, China
| | - Hongshan Xu
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Fang Wang
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Jiaomeng Zhu
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Pengfu Tian
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Kezhen Yi
- Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Qian Zhang
- Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Hui Xiao
- Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Yongwei Duan
- Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Wei Li
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Linlu Ma
- Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Fuling Zhou
- Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Yanxiang Cheng
- School of Medicine, Renmin Hospital, Wuhan University, Wuhan 430060, China
| | - Long Bai
- School of Medicine, Zhejiang University, Zhejiang 310002, China
| | - Fubing Wang
- Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
| | - Xuan Xiao
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China
| | - Yimin Zhu
- School of Medicine, Zhejiang University, Zhejiang 310002, China
| | - Yi Yang
- Department of Clinical Laboratory, Institute of Translational Medicine, Institute of Medicine and Physics, Renmin Hospital of Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics & Technology, Wuhan University, Wuhan 430072, China; Shenzhen Research Institute, Wuhan University, Shenzhen 518000, China.
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14
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Raikar AS, Priya S, Bhilegaonkar SP, Somnache SN, Kalaskar DM. Surface Engineering of Bioactive Coatings for Improved Stent Hemocompatibility: A Comprehensive Review. MATERIALS (BASEL, SWITZERLAND) 2023; 16:6940. [PMID: 37959540 PMCID: PMC10650382 DOI: 10.3390/ma16216940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 10/21/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023]
Abstract
Cardiovascular diseases continue to be a major contributor to illness and death on a global scale, and the implementation of stents has given rise to a revolutionary transformation in the field of interventional cardiology. The thrombotic and restenosis complications associated with stent implantation pose ongoing challenges. In recent years, bioactive coatings have emerged as a promising strategy to enhance stent hemocompatibility and reduce thrombogenicity. This review article provides an overview of the surface engineering techniques employed to improve the hemocompatibility of stents and reduce thrombus formation. It explores the mechanisms underlying thrombosis and discusses the factors influencing platelet activation and fibrin formation on stent surfaces. Various bioactive coatings, including anticoagulant agents, antiplatelet agents, and surface modifications, are discussed in detail, highlighting their potential in reducing thrombogenicity. This article also highlights a multitude of surface modification techniques which can be harnessed to enhance stent hemocompatibility including plasma treatment, physical vapor deposition (PVD), chemical vapor deposition (CVD), and electrodeposition. These techniques offer precise control over surface properties such as roughness, charge, and composition. The ultimate goal is to reduce platelet adhesion, tailor wettability, or facilitate the controlled release of bioactive agents. Evaluation methods for assessing hemocompatibility and thrombogenicity are also reviewed, ranging from in vitro assays to animal models. Recent advances in the field, such as nanotechnology-based coatings and bioactive coatings with controlled drug release systems, are highlighted. Surface engineering of bioactive coatings holds great promise for enhancing the long-term outcomes of stent implantation by enhancing hemocompatibility and reducing thrombogenicity. Future research directions and potential clinical applications are discussed, underscoring the need for continued advancements in this field.
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Affiliation(s)
- Amisha S. Raikar
- Department of Pharmaceutics, PES Rajaram and Tarabai Bandekar College of Pharmacy, Ponda 403401, India;
| | - Sushma Priya
- University College of London, Division of Surgery and Interventional Science, Royal National Orthopaedic Hospital, Rowland Hill Street, London NW3 2PF, UK;
- Department of Biomedical Engineering, Regenerative Medicine and Stem Cell (RMS) Labs, Indian Institute of Technology, Hyderabad 502285, India
| | - Shilpa P. Bhilegaonkar
- Department of Pharmaceutics, PES Rajaram and Tarabai Bandekar College of Pharmacy, Ponda 403401, India;
| | - Sandesh N. Somnache
- Department of Pharmaceutics, SSPM’s VP College of Pharmacy, Madkhol 416510, India;
| | - Deepak M. Kalaskar
- University College of London, Division of Surgery and Interventional Science, Royal National Orthopaedic Hospital, Rowland Hill Street, London NW3 2PF, UK;
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15
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Aizawa T, Inoue Y, Ito S, Morimoto S, Ogawa K, Nagoshi T, Minai K, Ogawa T, Kawai M, Yoshimura M. Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease. Heart Vessels 2023; 38:1218-1227. [PMID: 37318650 PMCID: PMC10465654 DOI: 10.1007/s00380-023-02279-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 06/07/2023] [Indexed: 06/16/2023]
Abstract
Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36 months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36 months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36 months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.
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Affiliation(s)
- Takatoku Aizawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yasunori Inoue
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Satoshi Ito
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Satoshi Morimoto
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kazuo Ogawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Tomohisa Nagoshi
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kosuke Minai
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takayuki Ogawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Makoto Kawai
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Michihiro Yoshimura
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
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16
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Ponchia PI, Ahmed R, Farag M, Alkhalil M. Antiplatelet Therapy in End-stage Renal Disease Patients on Maintenance Dialysis: a State-of-the-art Review. Cardiovasc Drugs Ther 2023; 37:975-987. [PMID: 35867319 DOI: 10.1007/s10557-022-07366-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/06/2022] [Indexed: 11/03/2022]
Abstract
Patients with end-stage renal disease (ESRD) on maintenance dialysis have an increased risk of ischaemic events, such as recurrent myocardial infarction (MI) and stroke. Potent antiplatelet therapy may help mitigate this risk. Nonetheless, ERSD patients are also at increased risk of bleeding due to their complex vascular milieu, which limits the routine use of potent P2Y12 inhibitors. Moreover, these patients are often underrepresented or excluded from major clinical trials leaving a significant gap in existing knowledge. Understanding the mechanisms of this paradox may serve as a benchmark for the development of ESRD trials. The present review aims to provide an overview of the pathophysiological nature of increased bleeding and ischaemic risks in ERSD patients as well as summarize available evidence of antiplatelet use and propose new concepts to guide physicians in selecting appropriate drug regimes for this high-risk cohort.
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Affiliation(s)
| | | | - Mohamed Farag
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Mohammad Alkhalil
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, NE7 7DN, UK.
- Department of Cardiothoracic Services, Freeman Hospital, Freeman Road, Newcastle-upon-Tyne, NE7 7DN, UK.
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17
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Guardieiro B, Santos-Paul MA, Furtado RHDM, Dalçóquio T, Salsoso R, Neves ILI, Neves RS, Cavalheiro Filho C, Baracioli LM, Nicolau JC. Comparison between two different local hemostatic methods for dental extractions in patients on dual antiplatelet therapy: a within-person, single-blind, randomized study. J Evid Based Dent Pract 2023; 23:101863. [PMID: 37689449 DOI: 10.1016/j.jebdp.2023.101863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 03/09/2023] [Accepted: 04/03/2023] [Indexed: 09/11/2023]
Abstract
BACKGROUND Dual antiplatelet therapy (DAPT) provides additional risk reduction of ischemic events compared to aspirin monotherapy, at cost of higher bleeding risk. There are few data comparing new techniques for reducing bleeding after dental extractions in these patients. PURPOSE This study investigated the effectiveness of the HemCon Dental Dressing (HDD) compared to oxidized cellulose gauze. MATERIALS AND METHODS This randomized study included 60 patients on DAPT who required at least two dental extractions (120 procedures). Each surgical site was randomized to HDD or oxidized regenerated cellulose gauze as the local hemostatic method. Intra-oral bleeding time was measured immediately after the dental extraction and represents our main endpoint for comparison of both hemostatic agents. Prolonged bleeding, platelet reactivity measured by Multiplate Analyser (ADPtest and ASPItest) and tissue healing comparison after 7 days were also investigated. RESULTS Intra-oral bleeding time was lower in HDD compared with control (2 [2-5] vs. 5 [2-8] minutes, P=0.001). Prolonged postoperative bleeding was observed in 7 cases (11.6%), all of them successfully managed with local sterile gauze pressure. More HDD treated sites presented better healing when compared with control sites [21 (36.8%) vs. 5 (8.8%), P=0.03]. There was poor correlation between platelet reactivity and intra-oral bleeding time. CONCLUSIONS In patients on DAPT, HDD resulted in a lower intra-oral bleeding time compared to oxidized cellulose gauze after dental extractions. Moreover, HDD also seems to improve healing conditions.
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Affiliation(s)
- Bruno Guardieiro
- Instituto do Coracao (InCor), Unidade de Odontologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Marcela Alves Santos-Paul
- Instituto do Coracao (InCor), Unidade de Odontologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Remo Holanda de Mendonça Furtado
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil; Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Talia Dalçóquio
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Rocío Salsoso
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Itamara Lúcia Itagiba Neves
- Instituto do Coracao (InCor), Unidade de Odontologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Ricardo Simões Neves
- Instituto do Coracao (InCor), Unidade de Odontologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Cyrillo Cavalheiro Filho
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - Luciano Moreira Baracioli
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
| | - José Carlos Nicolau
- Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.
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18
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Kuno T, Watanabe A, Shoji S, Fujisaki T, Ueyama H, Takagi H, Deharo P, Cuisset T, Bangalore S, Mehran R, Stone GW, Kohsaka S, Bhatt DL. Short-Term DAPT and DAPT De-Escalation Strategies for Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis. Circ Cardiovasc Interv 2023; 16:e013242. [PMID: 37609850 DOI: 10.1161/circinterventions.123.013242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/13/2023] [Indexed: 08/24/2023]
Abstract
BACKGROUND Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. METHODS A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y12 inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. RESULTS This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y12 inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y12 inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y12 inhibitor was ranked the best for major bleeding and all-cause death. CONCLUSIONS In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y12 inhibitor was associated with the lowest risk of major bleeding and all-cause death.
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Affiliation(s)
- Toshiki Kuno
- Division of Cardiology, Montefiore Medical Center (T.K.), Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY
- Division of Cardiology (T.K.), Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY
| | - Atsuyuki Watanabe
- Department of Medicine, Mount Sinai Beth Israel (A.W.), Icahn School of Medicine at Mount Sinai, New York, NY
| | - Satoshi Shoji
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (S.S., S.K.)
- Duke Clinical Research Institute, Durham, NC (S.S.)
| | - Tomohiro Fujisaki
- Department of Medicine, Mount Sinai Morningside and West (T.F.), Icahn School of Medicine at Mount Sinai, New York, NY
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan (T.F.)
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (T.F.)
| | - Hiroki Ueyama
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (H.U.)
| | - Hisato Takagi
- Department of Cardiovascular Surgery, Shizuoka Medical Center, Japan (H.T.)
| | - Pierre Deharo
- Département de Cardiologie, CHU Timone, Marseille, France (P.D., T.C.)
- INSERM, INRA, C2VN (P.D., T.C.), Aix-Marseille Université, France
- Faculté de Médecine (P.D., T.C.), Aix-Marseille Université, France
| | - Thomas Cuisset
- Département de Cardiologie, CHU Timone, Marseille, France (P.D., T.C.)
- INSERM, INRA, C2VN (P.D., T.C.), Aix-Marseille Université, France
- Faculté de Médecine (P.D., T.C.), Aix-Marseille Université, France
| | - Sripal Bangalore
- Leon H. Charney Division of Cardiovascular Medicine, New York University Grossman School of Medicine (S.B.)
| | - Roxana Mehran
- The Zena and Michael A. Wiener Cardiovascular Institute (R.M., G.W.S.), Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gregg W Stone
- The Zena and Michael A. Wiener Cardiovascular Institute (R.M., G.W.S.), Icahn School of Medicine at Mount Sinai, New York, NY
| | - Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (S.S., S.K.)
| | - Deepak L Bhatt
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY (D.L.B.)
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19
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Virk HUH, Escobar J, Rodriguez M, Bates ER, Khalid U, Jneid H, Birnbaum Y, Levine GN, Smith SC, Krittanawong C. Dual Antiplatelet Therapy: A Concise Review for Clinicians. Life (Basel) 2023; 13:1580. [PMID: 37511955 PMCID: PMC10381391 DOI: 10.3390/life13071580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/05/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular events, and myocardial infarction rates but increases bleeding risk. Extended DAPT does not significantly benefit stable coronary artery disease patients in reducing stroke, myocardial infarction, or cardiovascular death. Ticagrelor and aspirin reduce cardiovascular events in stable coronary artery disease with diabetes but carry a higher bleeding risk. Antiplatelet therapy duration in atrial fibrillation patients after percutaneous coronary intervention depends on individual characteristics and bleeding risk. Antiplatelet therapy is crucial for post-coronary artery bypass graft and transcatheter aortic valve implantation; Aspirin (ASA) monotherapy is preferred. Antiplatelet therapy duration in peripheral artery disease depends on the scenario. Adding vorapaxar and cilostazol may benefit secondary prevention and claudication, respectively. Carotid artery disease patients with transient ischemic attack or stroke benefit from antiplatelet therapy and combining ASA and clopidogrel is more effective than ASA alone. The optimal duration of DAPT after carotid artery stenting is uncertain. Resistance to ASA and clopidogrel poses an incremental risk of deleterious cardiovascular events and stroke. The selection and duration of antiplatelet therapy in patients with cardiovascular disease requires careful consideration of both efficacy and safety outcomes. The use of combination therapies may provide added benefits but should be weighed against the risk of bleeding. Further research and clinical trials are needed to optimize antiplatelet treatment in different patient populations and clinical scenarios.
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Affiliation(s)
- Hafeez Ul Hassan Virk
- Harrington Heart & Vascular Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH 44101, USA
| | - Johao Escobar
- International Transitional Medical Graduate, American College of Physician, Philadelphia, PA 19106, USA
| | - Mario Rodriguez
- John T Milliken Department of Medicine, Division of Cardiovascular Disease, Section of Advanced Heart Failure and Transplant, Barnes-Jewish Hospital, Washington University, St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Eric R Bates
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Umair Khalid
- Michael E. DeBakey VA Medical Center, Section of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Hani Jneid
- Division of Cardiology, University of Texas Medical Branch, Houston, TX 77555, USA
| | - Yochai Birnbaum
- Michael E. DeBakey VA Medical Center, Section of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Glenn N Levine
- Michael E. DeBakey VA Medical Center, Section of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sidney C Smith
- Division of Cardiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Chayakrit Krittanawong
- Cardiology Division, NYU School of Medicine, NYU Langone Health, New York, NY 10016, USA
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20
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Lee YC, Liao YC, Lin CJ, Chung CP. Baseline P2Y12 reactivity, kidney function, and CYP2C19 genotype determine clopidogrel responsiveness in acute stroke. Sci Rep 2023; 13:8085. [PMID: 37208337 DOI: 10.1038/s41598-023-34481-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 05/02/2023] [Indexed: 05/21/2023] Open
Abstract
Clopidogrel is the most-widely used platelet P2Y12-inhibitor for secondary-prevention of ischemic stroke. Platelet P2Y12 reactivity before and after inhibitors can be measured with blood sampling by commercialized system. We aimed to evaluate (1) whether high-on-clopidogrel platelet P2Y12 reactivity (HCPR) is associated with short-term vascular events and (2) the predictors of HCPR in acute stroke. The inclusion criterion was patients with acute stroke who received clopidogrel within 12-48 h after the onset. Platelet reactivity was assayed at baseline and after clopidogrel treatment using the VerifyNow system. The primary endpoint was recurrent ischemic events within 21 days after stroke. Among 190 patients, 32(16.9%) had recurrent ischemic stroke. Multivariate analyses showed that HCPR was significantly associated with the short-term events with an odds-ratio of 2.5 (95% CI 1.1-5.7, p = 0.027). Patients with HCPR had significantly higher frequencies of high baseline platelet P2Y12 reactivity, impaired kidney function, and carrying one or two CYP2C19 loss-of-function alleles. A poor clopidogrel response score combining these factors was developed. Ten percent of patients with score 0, 20.3% of those with score 1, 38.3% of those with score 2, and 66.7% of those with score 3 had HCPR (χ2-test, p < 0.001). Multivariate analyses showed that, compared with the score-0 group, the score-2 and -3 groups had higher risks of HCPR with hazard-ratios of 5.4 (95% CI 1.5-20.3, p = 0.012) and 17.4 (95% CI 3.4-88.9, p = 0.001) for developing recurrent ischemic strokes. The study emphasized the role of HCPR in ischemic stroke. We also developed an HCPR risk score, which could be used in clinical practice or trials, potentially with more precision, to weigh the clinical benefit of a tailored antiplatelet-strategy for patients with stroke.
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Affiliation(s)
- Yi-Chung Lee
- Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan
- Department of Neurology, School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
| | - Yi-Chu Liao
- Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan
- Department of Neurology, School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
| | - Chun-Jen Lin
- Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan
- Department of Neurology, School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
| | - Chih-Ping Chung
- Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan.
- Department of Neurology, School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan.
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21
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Simonte G, Guglielmini G, Falcinelli E, Isernia G, Mezzasoma AM, Gresele P, Lenti M. High-on-treatment platelet reactivity predicts adverse outcome after carotid artery stenting: A prospective study. Thromb Res 2023; 222:117-123. [PMID: 36640567 DOI: 10.1016/j.thromres.2022.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/15/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND PURPOSE High-on-treatment platelet reactivity (HTPR) has been established as a predictor of major adverse cardiovascular events (MACE) in patients undergoing percutaneous coronary interventions on dual antiplatelet therapy (DAPT), but no data are available on its predictive value in patients on DAPT after carotid artery stenting (CAS). We aimed to evaluate the possible association between HTPR in patients on aspirin plus clopidogrel therapy after CAS and subsequent MACE. METHODS All consecutive patients treated with CAS in a single institution were enrolled in a prospective clinical study. HTPR was evaluated with 5 different laboratory assays carried out just before CAS. MACE incidence (cerebral ischemia, myocardial infarction, stent thrombosis, acute limb ischemia and vascular death) was evaluated at 30 days and thereafter at yearly visits. RESULTS A total of 300 patients were enrolled in the study, and eight were then excluded because blood samples resulted unsuitable for the laboratory testing or CAS aborted for technical problems. Median follow-up was 5.8 years and during this period 47 MACE occurred. HTPR detected by multiplate electronic aggregometry (MEA) and the VASP phosphorylation assay (VASP) were associated with a significantly enhanced risk of MACE (p = 0.048 and p = 0.038, respectively). However, HTPR to three tests (HTPR3) was more strongly predictive of increased risk of a vascular event at follow up (p = 0.005) at bivariate analysis and also at Cox regression multivariate analysis (p = 0.002). CONCLUSIONS HTPR to three different assays (mainly to VASP + PFA P2Y+ VerifyNow) in patients on DAPT after CAS has predictive value for subsequent MACE. Prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard DAPT in patient undergoing CAS should be considered.
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Affiliation(s)
- G Simonte
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
| | - G Guglielmini
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - E Falcinelli
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - G Isernia
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
| | - A M Mezzasoma
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - P Gresele
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - M Lenti
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
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22
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Davidson S. Monitoring of Antiplatelet Therapy. Methods Mol Biol 2023; 2663:381-402. [PMID: 37204725 DOI: 10.1007/978-1-0716-3175-1_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
In the late 1990s, the antithrombotic antiplatelet agent, clopidogrel, a P2Y12 inhibitor, was introduced. Around the same time, there was an increase in a number of new methods to measure platelet function (e.g., PFA-100 in 1995), and this has continued. It became evident that not all patients responded to clopidogrel in the same way and that some patients had a relative "resistance" to therapy, termed "high on-treatment platelet reactivity." This then led to some publications to advocate platelet function testing being used for patients on antiplatelet therapy. Platelet function testing was also suggested for use in patients awaiting cardiac surgery after stopping their antiplatelet therapy as a way of balancing thrombotic risk pre-surgery and bleeding risk perioperatively. This chapter will discuss some of the commonly used platelet function tests used in these settings, particularly those that are sometimes referred to as point-of-care tests or that require minimal laboratory sample manipulation. The latest guidance and recommendations for platelet function testing will be discussed following several clinical trials looking at the usefulness of platelet function testing in these clinical settings.
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Affiliation(s)
- Simon Davidson
- Division of Medicine, University College London, London, UK.
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23
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Jin Y, Ma J, Wang Z, Zou Y, Wang G, Wu Y, Wang Y, Liu H, Yin T, Ye P. Performance of the ABCD-GENE Score for Predicting Clinical Outcomes in Clopidogrel-Treated Patients with ACS. J Cardiovasc Transl Res 2022; 15:1385-1392. [PMID: 35437618 DOI: 10.1007/s12265-022-10255-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 04/04/2022] [Indexed: 12/16/2022]
Abstract
The ABCD-GENE score was constructed to identify patients with high platelet reactivity (HPR) after 30 days of clopidogrel treatment. In our study, 1297 eligible patients with acute coronary syndrome (ACS) were included, and 44 (3.4%) major adverse cardiovascular events (MACEs) occurred during the 12-month clopidogrel treatment. The score with a cutoff of ≥ 10 was independently associated with the risk of 5-day HPR (adjusted HR: 1.73, 95% CI: 1.09-2.74, P = 0.020) and MACEs (adjusted HR: 2.25, 95% CI: 1.19-4.25, P = 0.013). The risk of MACEs increased when the multivariable model with the score (≥ 10) plus 5-day HPR was used (adjusted HR: 4.37, 95% CI: 1.90-10.10, P = 0.001). The c-statistic for MACEs was 0.60 when using the score threshold of ≥ 10 and 0.63 when using the model with the score plus 5-day HPR. As a simple tool, the ABCD-GENE score could identify clopidogrel-treated Chinese patients with ACS who are at increased risk of MACEs. The addition of 5-day HPR could slightly improve the diagnostic ability of the score.
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Affiliation(s)
- Ying Jin
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
- Department of Geriatrics, Air Force Medical Center of Chinese PLA, Beijing, 100141, China
| | - Jing Ma
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
- Senior Department of Cardiology, the Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100142, China
| | - Ziqian Wang
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Yuting Zou
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Guanyun Wang
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Yangxun Wu
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Yuyan Wang
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Haiping Liu
- Medical School of Chinese PLA, Beijing, 100853, China
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China
| | - Tong Yin
- Medical School of Chinese PLA, Beijing, 100853, China.
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China.
| | - Ping Ye
- Medical School of Chinese PLA, Beijing, 100853, China.
- Institute of Geriatrics and Department of Cardiology, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China.
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24
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Marcano AL, Gracida M, Roura G, Gomez-Lara J, Romaguera R, Teruel L, Fuentes L, Muntané-Carol G, Meroño O, Sosa SG, Gómez-Hospital JA, Comin-Colet J, Ferreiro JL. Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation. Front Cardiovasc Med 2022; 9:1057331. [PMID: 36483622 PMCID: PMC9722765 DOI: 10.3389/fcvm.2022.1057331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/03/2022] [Indexed: 09/10/2024] Open
Abstract
Introduction Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. Materials and methods In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. Results The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 μM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. Conclusion In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. Clinical trial registration [ClinicalTrials.gov], identifier [NCT02457130].
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Affiliation(s)
- Ana Lucrecia Marcano
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Montserrat Gracida
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Gerard Roura
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Josep Gomez-Lara
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Rafael Romaguera
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Luis Teruel
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Lara Fuentes
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Guillem Muntané-Carol
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Oona Meroño
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Faculty of Medicine, University of Vic-Central University of Catalonia, Barcelona, Spain
| | - Silvia Gabriela Sosa
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Joan Antoni Gómez-Hospital
- Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Josep Comin-Colet
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Cardiology, Bellvitge University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, L’Hospitalet de Llobregat, Barcelona, Spain
| | - José Luis Ferreiro
- Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Cardiology, Bellvitge University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, L’Hospitalet de Llobregat, Barcelona, Spain
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25
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Mazzone PM, Angiolillo DJ, Capodanno D. Approaches to de-escalation of antiplatelet treatment in stabilized post-myocardial infarction patients with high ischemic risk. Expert Rev Cardiovasc Ther 2022; 20:839-849. [DOI: 10.1080/14779072.2022.2137492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Affiliation(s)
- Placido Maria Mazzone
- Division of Cardiology, Azienda Ospedaliero-Universitaria Policlinico “G. Rodolico – San Marco” University of Catania, Catania, Italy
| | - Dominick J. Angiolillo
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Davide Capodanno
- Division of Cardiology, Azienda Ospedaliero-Universitaria Policlinico “G. Rodolico – San Marco” University of Catania, Catania, Italy
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26
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Numasawa Y. Impact of Platelet Reactivity on Ischemic and Bleeding Events After Percutaneous Coronary Intervention - A Long-Term Perspective. Circ J 2022; 86:1350-1351. [PMID: 35650117 DOI: 10.1253/circj.cj-22-0297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Yohei Numasawa
- Department of Cardiology, Japanese Red Cross Ashikaga Hospital
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27
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Shi QP, Luo XY, Zhang B, Wang XG, Zhao J, Xie QF, Liu JH, Liu YK, Jiang J, Zheng B. Effect of indobufen vs. aspirin on platelet accumulation in patients with stable coronary heart disease after percutaneous coronary intervention: An open-label crossover study. Front Pharmacol 2022; 13:950719. [PMID: 36052139 PMCID: PMC9424757 DOI: 10.3389/fphar.2022.950719] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/18/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose: This study compared the effect of indobufen with that of aspirin on platelet function in patients with stable coronary heart disease after percutaneous coronary intervention (PCI). Methods: Patients with stable coronary heart disease who had undergone PCI and received dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg once daily) for at least 12 months were allocated to receive indobufen 100 mg twice daily + clopidogrel 75 mg once daily, clopidogrel 75 mg once daily alone, indobufen 100 mg twice daily alone, and aspirin 100 mg once daily alone for 1 month each in an open-label crossover manner. Platelet function was assessed by using the rates of arachidonic acid (AA)-induced platelet aggregation (AA-PAR) and adenosine diphosphate (ADP)-induced platelet aggregation (ADP-PAR) measured by light transmission aggregometry, the platelet reactivity index measured by vasodilator-stimulated phosphoprotein (PRI-VASP), and the plasma and urinary thromboxane B2 (TXB2) concentrations recorded at baseline and during each treatment phase. Results: Of 56 patients enrolled, 52 completed the study. The AA-PAR was lower in the indobufen alone group than in the aspirin alone group [5.21% (3.39, 7.98) vs. 5.27% (4.06, 6.60), p = 0.038], while biologically, a difference of 0.06% may represent no significant difference; there was no significant between-group difference in the plasma [531.16 pg/ml (203.89, 1035.06) vs. 373.93 pg/ml (194.04, 681.71), p = 0.251] or urinary [3951.97 pg/ml (2006.95, 6077.01) vs. 3610.48 pg/ml (1664.60, 6247.61), p = 0.717] TXB2 concentration. When the aspirin + clopidogrel group and indobufen + clopidogrel group were compared, similar results were found for AA-PAR [3.97% (3.05, 5.12) vs. 3.83% (3.10, 5.59), p = 0.947] and both plasma [849.47 pg/ml (335.96, 1634.54) vs. 455.41 pg/ml (212.47, 1489.60), p = 0.629], and urinary [4122.97 pg/ml (2044.96, 7459.86) vs. 3812.81 pg/ml (1358.95, 6021.07), p = 0.165] TXB2 concentrations. ADP-PAR was lower in the clopidogrel alone group than in the indobufen alone group (47.04% ± 16.89 vs. 61.7% ± 10.50, p < 0.001), as was PRI-VASP (66.53% ± 18.06 vs. 77.72% ± 19.87, p = 0.002). Conclusion: These findings suggest that indobufen has antiplatelet effects similar to those of aspirin in patients with stable coronary heart disease after PCI, and may be an alternative for patients with aspirin intolerance after coronary stenting.
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Affiliation(s)
- Qiu-Ping Shi
- Peking University First Hospital, Beijing, China
| | - Xing-Yu Luo
- Peking University First Hospital, Beijing, China
| | - Bin Zhang
- Peking University First Hospital, Beijing, China
| | | | - Jing Zhao
- Peking University First Hospital, Beijing, China
| | - Qiu-Fen Xie
- Peking University First Hospital, Beijing, China
| | - Jia-Hui Liu
- Peking University First Hospital, Beijing, China
| | - Yao-Kun Liu
- Peking University First Hospital, Beijing, China
| | - Jie Jiang
- Peking University First Hospital, Beijing, China
- Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, China
| | - Bo Zheng
- Peking University First Hospital, Beijing, China
- Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, China
- *Correspondence: Bo Zheng,
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Kuno T, Fujisaki T, Shoji S, Sahashi Y, Tsugawa Y, Iwagami M, Takagi H, Briasoulis A, Deharo P, Cuisset T, Latib A, Kohsaka S, Bhatt DL. Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis. Circ Cardiovasc Interv 2022; 15:e011990. [PMID: 35899618 DOI: 10.1161/circinterventions.122.011990] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The benefit of dual antiplatelet therapy (DAPT) for reducing ischemic events is greatest in the early period of acute coronary syndrome, and recent randomized controlled trials have investigated the unguided de-escalation strategy of changing potent P2Y12 inhibitors to less potent or reduced-dose P2Y12 inhibitors 1 month after acute coronary syndrome. However, it remains unclear which strategy is more effective and safer: the uniform unguided de-escalation strategy versus the personalized guided selection of DAPT with genotype or platelet function tests. METHODS PubMed, EMBASE, and Cochrane Central were searched for articles published from database inception to September 10, 2021. Randomized controlled trials investigating DAPT using clopidogrel, low-dose prasugrel, standard-dose prasugrel, ticagrelor, unguided de-escalation strategy, and guided selection strategy for patients with acute coronary syndrome were included. Hazard ratios and relative risk estimates were extracted from each study. The estimates were pooled using a random-effects network meta-analysis. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and major bleeding. RESULTS This study included 19 randomized controlled trials with 69 746 patients. Compared with guided selection of DAPT, unguided de-escalation of DAPT was associated with a decreased risk of the primary safety outcome (hazard ratio, 0.48 [95% CI, 0.33-0.72]) without increased risks of major adverse cardiovascular events (hazard ratio, 0.82 [95% CI, 0.53-1.28]) or any secondary outcomes. The results were similar when the guided selection strategy was divided into platelet function-guided and genotype-guided strategies. CONCLUSIONS Compared with guided selection of DAPT, unguided de-escalation of DAPT decreased bleeding without increasing ischemic events in patients after acute coronary syndrome. If a strategy of de-escalation is chosen, these findings do not support the routine use of personalized guiding tests. REGISTRATION URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021273082.
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Affiliation(s)
- Toshiki Kuno
- Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (T.K., A.L.).,Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY (T.K.)
| | - Tomohiro Fujisaki
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan (T.F.).,Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Morningside and West, New York, NY (T.F.)
| | - Satoshi Shoji
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (S.S., S.K.)
| | - Yuki Sahashi
- Department of Cardiology, Gifu University, Japan (Y.S.)
| | - Yusuke Tsugawa
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, Los Angeles, CA (Y.T.).,Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (Y.T.)
| | - Masao Iwagami
- Department of Health Services Research, University of Tsukuba, Japan (M.I.)
| | - Hisato Takagi
- Department of Cardiovascular Surgery, Shizuoka Medical Center, Japan (H.T.)
| | - Alexandros Briasoulis
- Division of Cardiology, Heart Failure and Transplantation, University of Iowa' Iowa City (A.B.)
| | - Pierre Deharo
- Département de Cardiologie, CHU Timone, Marseille, France (P.D., T.C.).,Center for Cardiovascular and Nutrition Research, INSERM, INRA (P.D., T.C.), Aix-Marseille Université, France.,Faculté de Médecine (P.D., T.C.), Aix-Marseille Université, France
| | - Thomas Cuisset
- Département de Cardiologie, CHU Timone, Marseille, France (P.D., T.C.).,Center for Cardiovascular and Nutrition Research, INSERM, INRA (P.D., T.C.), Aix-Marseille Université, France.,Faculté de Médecine (P.D., T.C.), Aix-Marseille Université, France
| | - Azeem Latib
- Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (T.K., A.L.)
| | - Shun Kohsaka
- Department of Cardiology, Gifu University, Japan (Y.S.)
| | - Deepak L Bhatt
- Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.)
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Xu Y, Chen W, Jiang L, Wang Y, Zhao X, Liu L, Yao D, Guo L, Wang Y, Pan Y, Wang Y. Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack. J Stroke Cerebrovasc Dis 2022; 31:106683. [PMID: 35914511 DOI: 10.1016/j.jstrokecerebrovasdis.2022.106683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 07/18/2022] [Accepted: 07/22/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial. MATERIALS AND METHODS Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y12 assay for P2Y12 reaction units (PRU); HPR to P2Y12 was defined as >208 PRU (poor response to P2Y12). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days. RESULTS Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%). CONCLUSIONS In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.
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Affiliation(s)
- Yanjie Xu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Department of Neurology, Beijing Long Fu Hospital, Beijing, China
| | - Weiqi Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Lingling Jiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yicong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Liping Liu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Dongxiao Yao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Lei Guo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
| | - Yilong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
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Peng W, Zhang Y, Lin Y. Low-dose and standard-dose ticagrelor compared with clopidogrel in patients with acute coronary syndromes: A cohort study from china. Front Cardiovasc Med 2022; 9:937261. [PMID: 35958420 PMCID: PMC9360550 DOI: 10.3389/fcvm.2022.937261] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/08/2022] [Indexed: 11/18/2022] Open
Abstract
Purpose Previous trials have demonstrated that ticagrelor was superior to clopidogrel in acute coronary syndrome (ACS) patients. However, several recent studies showed that ticagrelor was associated with a significantly higher risk of bleeding compared with clopidogrel, especially in East Asian patients. Low-dose ticagrelor might improve the safety of ACS patients in the Chinese population. Therefore, this study mainly explored the low-dose ticagrelor in Chinese ACS patients. Methods A total of 199 ACS patients were enrolled in this study. The maximum platelet aggregation rate induced by adenosine-5-diphosphate (ADP) was detected by light transmittance aggregometry (LTA). Platelet aggregation rate induced by ADP of more than or equal to 42.9% was defined as high on-treatment platelet reactivity (HPR) to P2Y12 inhibitors. All patients were followed up for at least 12 months. Clinical outcomes, changes of antiplatelet regimen, medication compliance and adverse reactions were collected. Results Patients were divided into three groups according to the P2Y12 inhibitors, including 87 cases in clopidogrel (75 mg once a day) group, 41 cases in ticagrelor 60 mg (twice a day) group, and 71 cases in ticagrelor 90 mg (twice a day) group. ADP-induced platelet aggregation rates in ticagrelor 60 mg group and 90 mg group were 28.4 (19.6, 42.9) and 22.33 (15.1, 34.7) respectively, which were significantly lower than those in clopidogrel group 49.3 (36.5, 61.0) with adjusted P < 0.001. At the same time, there was no significant difference in ADP-induced platelet aggregation rate between ticagrelor 60 mg and 90 mg group (adjusted P = 0.105). Compared with clopidogrel, the proportion of normal on-treatment platelet reactivity (NPR) of ticagrelor 60 mg and ticagrelor 90 mg were significantly higher than that of clopidogrel, and the proportion of NPR of ticagrelor 90 mg group was significantly higher than that of ticagrelor 60 mg group. Conclusions Patients of ticagrelor 60 mg and ticagrelor 90 mg had comparable platelet aggregation rates induced by ADP, and both of them had significantly more potent antiplatelet aggregation activity detected by LTA than clopidogrel.
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Affiliation(s)
- Wenxing Peng
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yunnan Zhang
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Yang Lin
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- *Correspondence: Yang Lin
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Sun Y, Liu R, Xia X, Xing L, Jiang J, Bian W, Zhang W, Wang C, Zhang C. Large-Scale Profiling on lncRNAs in Human Platelets: Correlation with Platelet Reactivity. Cells 2022; 11:cells11142256. [PMID: 35883699 PMCID: PMC9319970 DOI: 10.3390/cells11142256] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 07/12/2022] [Accepted: 07/18/2022] [Indexed: 11/16/2022] Open
Abstract
Recently, long noncoding RNAs (lncRNAs) have been key regulators for both mRNAs and proteins in nucleated cells. However, the expression profiles of lncRNAs in non-nucleated cells such as platelets are currently unclear. In this study, we determined the expression profiles of lncRNAs in human platelets. We found that 6109 lncRNAs were expressed in human platelets. Interestingly, 338 lncRNAs were differentially expressed in hyperreactive and hyporeactive platelets. Bioinformatics’ analysis revealed that these aberrantly expressed lncRNAs might be related to platelet activity and other platelet functions. To provide a proof of concept, we measured the expression levels of PARLncRNA-1, a down-regulated lncRNA of hyperreactive platelets, in platelets from 12 patients with acute myocardial infarction and their controls. We found that the lncRNA was also significantly down-regulated in platelets from patients, which was partially reversed by treatment with aspirin a known antiplatelet drug. LncRNAs may represent a novel class of modulators for platelet functions.
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Affiliation(s)
- Yeying Sun
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Rongrong Liu
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Xiangwen Xia
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Luchuan Xing
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Jing Jiang
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Weihua Bian
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
- Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA;
| | - Wendy Zhang
- Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA;
| | - Chunhua Wang
- US-China Institute for Translational Medicine, College of Pharmacy, Binzhou Medical University, Yantai 264000, China; (Y.S.); (R.L.); (X.X.); (L.X.); (J.J.); (W.B.); (C.W.)
| | - Chunxiang Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Nucleic Acid Medicine of Luzhou Key Laboratory, Metabolic Vascular Disease Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou 646000, China
- Correspondence: ; Tel.: +86-001-830-3162828
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Thomas CD, Franchi F, Keeley EC, Rossi JS, Winget M, David Anderson R, Dempsey AL, Gong Y, Gower MN, Kerensky RA, Kulick N, Malave JG, McDonough CW, Mulrenin IR, Starostik P, Beitelshees AL, Johnson JA, Stouffer GA, Winterstein AG, Angiolillo DJ, Lee CR, Cavallari LH. Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation. Clin Pharmacol Ther 2022; 112:146-155. [PMID: 35429163 PMCID: PMC9233085 DOI: 10.1002/cpt.2612] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/07/2022] [Indexed: 12/13/2022]
Abstract
The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.
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Affiliation(s)
- Cameron D Thomas
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Francesco Franchi
- Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA
| | - Ellen C Keeley
- Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Joseph S Rossi
- Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Marshall Winget
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - R David Anderson
- Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Alyssa L Dempsey
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Yan Gong
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Megan N Gower
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Richard A Kerensky
- Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Natasha Kulick
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jean G Malave
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Caitrin W McDonough
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Ian R Mulrenin
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Petr Starostik
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Amber L Beitelshees
- Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Julie A Johnson
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.,Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - George A Stouffer
- Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Almut G Winterstein
- Department of Pharmaceutical Outcomes & Policy and Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Dominick J Angiolillo
- Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA
| | - Craig R Lee
- Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Larisa H Cavallari
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA
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Zhou K, Yu S, Li J, Tan Y, Xing S, Chen Y, Ouyang F, Zeng J, Zhang J. High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis. Acta Neurol Scand 2022; 146:205-224. [PMID: 35652290 DOI: 10.1111/ane.13655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 05/05/2022] [Accepted: 05/11/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES High on-treatment platelet reactivity (HTPR) determined by platelet function assays is present in certain patients with ischemic stroke or transient ischemic attack (TIA). However, it is unclear whether HTPR is associated with poor clinical outcomes. Our study aimed to investigate the relationship of HTPR with recurrent vascular events in ischemic stroke or TIA. METHODS Pubmed (MEDLINE), EMBASE, and Cochrane Library were searched for eligible studies from inception to January 1, 2022. Stata 17.0 software was used to calculate the risk ratio (RR). Subgroup and sensitivity analyses were conducted to assess the source of heterogeneity. A random-effects model was used when heterogeneity was present. Primary endpoint of the meta-analysis was the risk ratio of recurrent vascular events in HTPR Patients. While stroke and TIA, all-cause death, early neurological deterioration, early new ischemic lesions, and stroke severity measured by National Institute of Health Stroke Scale (NIHSS) scores at admission were also pooled. RESULTS Thirty articles (7995 patients) were eligible including 28 cohort studies and 2 prospective case-control studies. The prevalence of HTPR varied from 5.9% to 60%. HTPR was associated with an increased risk of recurrent vascular events (RR = 2.94, 95% CI 2.04-4.23), stroke recurrence (RR = 2.05; 95% CI 1.43-2.95), and all-cause mortality (RR = 2.43; 95% CI 1.83-3.22). Subgroup analysis showed that HTPR determined by optical aggregometry, Verify-Now system and 11dh TXB2 is related to a higher risk of recurrent vascular events (RR = 3.53, 95% CI 1.51-9.40; RR = 2.16, 95% CI 1.02-4.56; RR = 3.76, 95% CI 1.51-9.40, respectively). Moreover, patients with HTPR had an increased incidence of early neurological deterioration (RR = 2.75; 95% CI 1.76-4.30) and higher NIHSS scores at admission (Mean difference 0.19, 95% CI 0.01-0.36). CONCLUSIONS This meta-analysis demonstrates HTPR is associated with higher risk of recurrent vascular events, early neurological deterioration and increased severity in patients with ischemic stroke and TIA. HTPR measured by platelet function assays may guide the use of antiplatelet agents in ischemic stroke and TIA.
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Affiliation(s)
- Kun Zhou
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Shiyuan Yu
- Zhongshan Medical College Sun Yat‐Sen University Guangzhou China
| | - Jingjing Li
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Yan Tan
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Shihui Xing
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Yicong Chen
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Fubing Ouyang
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Jinsheng Zeng
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
| | - Jian Zhang
- Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China
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Costa TGR, Katz M, Lemos PA, Guerra JCDC, Franken M, Pesaro AEP. Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor. EINSTEIN-SAO PAULO 2022; 20:eAO7001. [PMID: 35674593 PMCID: PMC9165567 DOI: 10.31744/einstein_journal/2022ao7001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 12/02/2021] [Indexed: 11/05/2022] Open
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Association Between Platelet Reactivity and Long-Term Bleeding Complications After Percutaneous Coronary Intervention According to Diabetes Status. Am J Cardiol 2022; 171:49-54. [PMID: 35277255 DOI: 10.1016/j.amjcard.2022.01.057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/04/2022] [Accepted: 01/17/2022] [Indexed: 12/12/2022]
Abstract
The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk.
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Roumeliotis A, Brilakis ES. PCI Strategies in Acute Coronary Syndromes without ST Segment Elevation (NSTE‐ACS). Interv Cardiol 2022. [DOI: 10.1002/9781119697367.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Mosconi MG, Paciaroni M, Ageno W. Investigational drugs for ischemic stroke: what's in the clinical development pipeline for acute phase and prevention? Expert Opin Investig Drugs 2022; 31:645-667. [PMID: 35486110 DOI: 10.1080/13543784.2022.2072725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Stroke is a leading cause of disability and mortality and its burden expected to increase. The only approved drug for acute ischemic stroke is the intravenous thrombolytic alteplase. The risk of bleeding complications is one of the reasons for the undertreatment of eligible patients. Numerous drugs are currently being developed to improve safety-efficacy. AREAS COVERED We reviewed literature from January 1st, 2000, to 15th January 2022 for the development and testing of novel drugs with the aim of targeting treatment at prevention of ischemic stroke: PubMed, MEDLINE, Google Scholar, and ClinicalTrial.gov. EXPERT OPINION The pathophysiology of ischemic stroke involves multiple pathways causing cerebral artery obstruction and brain tissue ischemia. Data suggest that tenecteplase is a more promising fibrinolytic agent with a superior efficacy-safety profile, compared to the currently approved alteplase. Current guidelines consider a short-term cycle of mannitol or hypertonic saline to be advisable in patients with space-occupying hemispheric infarction. Regarding primary and secondary prevention, research is primarily focused on identifying mechanisms to improve the safety-efficacy profile using a "hemostasis-sparing" approach. Further evaluation on those agents that have already shown promise for their risk/benefit profiles, would benefit greatly a neurologist's capacity to successfully prevent and treat ischemic stroke patients.
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Affiliation(s)
- Maria Giulia Mosconi
- Emergency and vascular medicine Stroke Unit University of Perugia, Perugia, Italy
| | - Maurizio Paciaroni
- Emergency and vascular medicine Stroke Unit University of Perugia, Perugia, Italy
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
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Song K, Jin X, Kim MH, Li JX, Jin CD, Yuan SL, Song ZY, Jin EZ, Lee KM, Lim KH, Cho YR. Differences in Optimal Platelet Reactivity after Potent P2Y12 Inhibitor Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention. J Clin Med 2022; 11:jcm11092480. [PMID: 35566604 PMCID: PMC9100277 DOI: 10.3390/jcm11092480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/29/2022] [Indexed: 01/23/2023] Open
Abstract
Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.
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Affiliation(s)
- Kai Song
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
- Department of Cardiology, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou 516002, China
| | - Xuan Jin
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
| | - Moo-Hyun Kim
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
- Correspondence: ; Tel.: +82-51-240-2976
| | - Jia-Xin Li
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (J.-X.L.); (E.-Z.J.)
| | - Cai-De Jin
- Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China;
| | - Song-Lin Yuan
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
| | - Zhao-Yan Song
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (J.-X.L.); (E.-Z.J.)
| | - En-Ze Jin
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (J.-X.L.); (E.-Z.J.)
| | - Kwang-Min Lee
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
| | - Kyung-Hee Lim
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
| | - Young-Rak Cho
- Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea; (K.S.); (X.J.); (S.-L.Y.); (Z.-Y.S.); (K.-M.L.); (K.-H.L.); (Y.-R.C.)
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Hokimoto S, Tsujita K, Ogawa H. Where Is the Significance of Measuring Platelet Function? Is the Answer in High Bleeding Risk Patients? Circ J 2022; 86:772-774. [PMID: 35046243 DOI: 10.1253/circj.cj-21-1049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
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Zou Y, Wang Y, Wu Y, Zhang S, Liu H, Yin T. Prediction of residual ischemic risk in ticagrelor-treated patients with acute coronary syndrome. Thromb J 2022; 20:21. [PMID: 35448998 PMCID: PMC9022318 DOI: 10.1186/s12959-022-00380-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/08/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Despite strong antiplatelet therapy with ticagrelor, serious ischemic events still occur in patients with acute coronary syndrome (ACS). The predictability of platelet reactivity to the residual risk of ischemic events during ticagrelor treatment remains uncertain. OBJECTIVES We aimed to investigate the predictability of the thromboelastography (TEG)-measured adenosine disphosphate (ADP)-induced platelet inhibition rate (ADP%) to the ischemic events in ticagrelor-treated patients with ACS. METHODS A cohort of ticagrelor-treated patients with ACS were consecutively recruited. ADP% was measured by TEG after 3 days of ticagrelor maintenance treatment. The primary ischemic event was defined as rehospitalization for unstable angina (UA) within 1 year, and the secondary ischemic event was a composite of the primary ischemic event plus all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, stroke, and unplanned revascularization within 1 year. RESULTS A total of 751 eligible patients with ACS were included in the analysis, with 336 patients randomly assigned to the derivation group and 415 to the validation group. The overall rates of primary and secondary ischemic events were 14.51% (n = 109) and 16.91% (n = 127), respectively. Compared to the patients without ischemic events, those with ischemic events had a significantly lower ADP% both in the derivation group (for primary ischemic events: 66.05% vs. 92.80%, p < 0.001; for secondary ischemic events: 66.05% vs. 93.20%, p < 0.001) and in the validation group (for primary ischemic events: 66.40% vs. 89.20%, p < 0.001; for secondary ischemic events: 66.90% vs. 89.20%, p < 0.001). Receiver operating characteristic curve (ROC) analysis showed that an ADP% < 76% was the optimal cut-off value for predicting 1-year primary ischemic events, with an area under the curve (AUC) of 0.80 (95% CI: 0.72-0.86, p < 0.001) in the derivation group and 0.77 (95% CI: 0.69-0.85, p < 0.001) in the validation group. The multivariate Cox regression hazard analysis consistently identified an ADP% < 76% as an independent predictor of primary ischemic events in the derivation group (HR: 8.21, 95% CI: 4.82-13.99, p < 0.001) and in the validation group (HR: 6.34 95% CI: 3.32-12.11, p < 0.001). There was also a strong association between an ADP% < 76 and the occurrence of secondary ischemic events in the derivation group (HR: 7.33, 95% CI: 4.47-12.00, p < 0.001) and in the validation group (HR: 4.76, 95% CI: 2.73-8.32, p < 0.001). CONCLUSION The ADP-induced platelet inhibition rate measured by TEG could predict ischemic events in ticagrelor-treated patients with ACS.
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Affiliation(s)
- Yuting Zou
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China.,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China.,Department of Cardiology, the 6th Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuyan Wang
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China.,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China
| | - Yangxun Wu
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China.,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China
| | - Shizhao Zhang
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China.,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China
| | - Haiping Liu
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China.,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China
| | - Tong Yin
- Institute of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China. .,Medical School of Chinese PLA, Chinese PLA General Hospital, 100853, Beijing, China.
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Patti G, Grisafi L, Spinoni E, Rognoni A, Mennuni MG. Safety and efficacy of selective, clopidogrel-based strategies in acute coronary syndrome: a study-level meta-analysis. Thromb Haemost 2022; 122:1732-1743. [PMID: 35436797 DOI: 10.1055/a-1827-8041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES To investigate outcome with selective, clopidogrel-based therapies vs conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. BACKGROUND Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. METHODS We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N=3,473; three on guided clopidogrel therapy, N=7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE) and net clinical endpoint. RESULTS The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy vs conventional treatment arm (OR 0·72, 95% CI 0·51-1·01, p=0·06; OR 0·93, 0·72-1·20, p=0·58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy vs conventional treatment group (OR 0·57, 0·40-0·80, p=0·001); this greater safety was significant for unguided de-escalation (OR 0·43, 0·32-0·58, p=0·00001) and non-significant for guided clopidogrel therapy (OR 0·72, 0·51-1·02, p=0·07; p for interaction 0·03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy vs conventional treatment arm (OR 0·59, 0·41-0·85, p=0·004); this benefit was significant for unguided de-escalation (OR 0·50, 0·39-0·64, p<0·00001) and non-significant for guided clopidogrel therapy (OR 0·85, 0·62-1·16, p=0·30; p for interaction 0·01). CONCLUSIONS As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.
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Affiliation(s)
- Giuseppe Patti
- Chair of Cardiology, University of Eastern Piedmont Amedeo Avogadro School of Medicine, RM, Italy
| | - Leonardo Grisafi
- University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Italy
| | - Enrico Spinoni
- Thoracic-Cardio-VAscular, University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Italy
| | - Andrea Rognoni
- Azienda Ospedaliero-Universitaria Maggiore della Carita, Novara, Italy
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Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7941039. [PMID: 35378909 PMCID: PMC8976642 DOI: 10.1155/2022/7941039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 12/16/2021] [Accepted: 02/11/2022] [Indexed: 11/18/2022]
Abstract
Background Tetramethylpyrazine (TMP) is an alkaloid in Chinese herbal medicine, which possesses antiplatelet activity. TMP inhibits platelet activation in many ways. The platelet P2Y12 receptor for adenosine 5′ diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Here, we investigated the inhibitory effect of TMP on P2Y12 receptor-related platelet function. Methods The inhibitory potential of TMP was assessed using agonist-induced platelet aggregation, flow cytometric analysis of CD62p expression, PAC-1 activation, and fibrin clot retraction. After the P2Y12 receptor-related signaling pathway was inhibited using the blocker, platelet activation was studied by platelet aggregation, CD62p expression, and PAC-1 activation. The secretion of cyclic adenosine monophosphate (cAMP) was measured using enzyme-linked immunosorbent assay (ELISA), and the expression of signaling pathway protein, phosphorylation of vasodilator-stimulated phosphoprotein, and phosphorylation of Akt were investigated using western blotting. The release of platelet inflammatory mediators was measured using ELISA. Results TMP had an antiplatelet effect by inhibiting ADP-induced aggregation, P-selectin secretion, and glycoprotein (GP) IIb/IIIa expression and reducing the release of atherosclerotic-related inflammatory mediators (sCD40L and IL-1β). TMP decreased the area of clot retraction, reflecting inhibition of GPIIb/IIIa activation. TMP inhibited adenosine diphosphate-induced platelet activation via increased cAMP production, VASPser157 phosphorylation, and Akt dephosphorylation. Conclusion TMP selectively inhibits ADP-induced platelet activation via P2Y12 receptor-related signaling pathways.
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Lin YJ, Jiao KL, Liu B, Fang L, Meng S. Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial. JOURNAL OF INTEGRATIVE MEDICINE 2022; 20:126-134. [PMID: 35101369 DOI: 10.1016/j.joim.2022.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/17/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.
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Affiliation(s)
- Yan-Jun Lin
- Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Kun-Li Jiao
- Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Bo Liu
- Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Lu Fang
- Haematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, VIC 3004, Australia
| | - Shu Meng
- Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
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Dutta R, Zouaoui Boudjeltia K, Kotsalos C, Rousseau A, Ribeiro de Sousa D, Desmet JM, Van Meerhaeghe A, Mira A, Chopard B. Personalized pathology test for Cardio-vascular disease: Approximate Bayesian computation with discriminative summary statistics learning. PLoS Comput Biol 2022; 18:e1009910. [PMID: 35271585 PMCID: PMC8939803 DOI: 10.1371/journal.pcbi.1009910] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/22/2022] [Accepted: 02/09/2022] [Indexed: 11/19/2022] Open
Abstract
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment.
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Affiliation(s)
| | - Karim Zouaoui Boudjeltia
- Laboratory of Experimental Medicine (ULB 222), Medicine Faculty, Université Libre de Bruxelles, ISPPC CHU de Charleroi, Charleroi, Belgium
| | | | - Alexandre Rousseau
- Laboratory of Experimental Medicine (ULB 222), Medicine Faculty, Université Libre de Bruxelles, ISPPC CHU de Charleroi, Charleroi, Belgium
| | - Daniel Ribeiro de Sousa
- Laboratory of Experimental Medicine (ULB 222), Medicine Faculty, Université Libre de Bruxelles, ISPPC CHU de Charleroi, Charleroi, Belgium
| | - Jean-Marc Desmet
- Nephrology Department, ISPPC CHU de Charleroi, Charleroi, Belgium
| | | | - Antonietta Mira
- Università della Svizzera italiana, Lugano, Switzerland
- University of Insubria, Varese, Italy
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Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Al-Mansori MA, Alali RA, Khalil RM, Al-Faraidy KA, Cyrus C, Sulieman MM, Vatte C, Loza BL, Claassens DMF, Asselbergs FW, Al-Ali AK. Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients. Int J Cardiol 2021; 343:15-20. [PMID: 34506827 DOI: 10.1016/j.ijcard.2021.08.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 08/28/2021] [Accepted: 08/31/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20-0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11-0.53), cardiovascular death (OR 0.16, 95%CI0.06-0.42) and major bleeding (OR 0.49, 95%CI 0.32-0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43-1.71). CONCLUSION A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.
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Affiliation(s)
- Abdullah M Al-Rubaish
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Fahad A Al-Muhanna
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Abdullah M Alshehri
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed A Al-Mansori
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Rudaynah A Alali
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Rania M Khalil
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Khalid A Al-Faraidy
- Department of Cardiology, King Fahd Armed Forces Hospital, Dhahran, Saudi Arabia
| | - Cyril Cyrus
- Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed M Sulieman
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Chittibabu Vatte
- Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Bao-Li Loza
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Folkert W Asselbergs
- Department of Cardiology, University Medical Center Utrecht, ICIN-Netherlands Heart Institute, Durrer Centre for Cardiogenetic Research, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
| | - Amein K Al-Ali
- Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
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Kirresh A, Candilio L, Stone GW. Intralesional delivery of glycoprotein IIb/IIIa inhibitors in acute myocardial infarction: Review and recommendations. Catheter Cardiovasc Interv 2021; 99:641-649. [PMID: 34767293 DOI: 10.1002/ccd.30008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 10/03/2021] [Accepted: 10/19/2021] [Indexed: 01/05/2023]
Abstract
Plaque rupture leads to a cascade of events culminating in collagen disruption, tissue factor release, platelet activation and thrombus formation. Pro-inflammatory conditions, hyperglycemia and smoking predispose to high thrombus burden (HTB) which is an independent predictor of slow or no-reflow. In patients with acute myocardial infarction (AMI), glycoprotein IIb/IIIa inhibitors (GPI) reduce thrombus burden and improve myocardial perfusion. These agents are typically administered systemically via the intravenous route or locally via an intracoronary (IC) route. However, as higher local concentrations of GPI are associated with enhanced platelet inhibition, intralesional (IL) GPI administration may be particularly effective in cases of HTB. Modest-sized randomized trials comparing IL and IC GPI delivery have reported conflicting outcomes. Some trials have demonstrated improved coronary flow and myocardial perfusion with reduced major adverse cardiac events with IL compared with IC GPI administration, whereas others have shown no significant benefits. Furthermore, although no direct comparison has been made between IL delivery using an aspiration catheter, microcatheter or a dedicated balloon-based "weeping" infusion-catheter, improved outcomes have been most consistent following GPI administration at the site of the lesion and thrombus with the dedicated infusion catheter. This review provides an update on the role and outcomes of IL GPI administration in patients with AMI and HTB. Based on the evidence we offer an algorithm demonstrating when to consider IL administration in patients with AMI undergoing intervention. We conclude with a perspective on the management of patients with STEMI and COVID-19 in whom a prothrombotic state often results in HTB.
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Affiliation(s)
- Ali Kirresh
- Cardiology Department, Royal Free London NHS Foundation Trust, London, UK
| | - Luciano Candilio
- Cardiology Department, Royal Free London NHS Foundation Trust, London, UK
| | - Gregg W Stone
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Cardiovascular Research Foundation, New York, New York, USA
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Duconge J, Santiago E, Hernandez‐Suarez DF, Moneró M, López‐Reyes A, Rosario M, Renta JY, González P, Ileana Fernández‐Morales L, Antonio Vélez‐Figueroa L, Arce O, Marín‐Maldonado F, Nuñez H, Melin K, Scott SA, Ruaño G. Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach. Clin Transl Sci 2021; 14:2254-2266. [PMID: 34415683 PMCID: PMC8604227 DOI: 10.1111/cts.13124] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/10/2021] [Accepted: 07/14/2021] [Indexed: 12/31/2022] Open
Abstract
This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on-clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole-genome Infinium MEGA BeadChip array. An ancestry-adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p < 0.001). PON1 rs662, ABCB1/MDR1 rs2032582, PEAR1 rs12041331 carrier status, and the interaction between African ancestry and rs12041331 carriers also predicted PRU among the participants (p ≤ 0.05). A clear gene-dose effect was detected between PRU and CYP2C19*2 genotype, consistent with previous studies in European patient populations, as well as rs12777823. Importantly, a significant positive correlation was detected between our novel wPGxRS (4 variants) and PRU among the Hispanic patient population (rp = 0.35, p < 0.001). Moreover, the wPGxRS discriminated between nonresponders and responders (p = 0.003), indicating that this multigene-based score is a useful predictor of clopidogrel resistance among Caribbean Hispanics. Taken together, these results help close the gap of knowledge on clopidogrel pharmacogenomics and its potential clinical implementation in this under-represented population.
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Affiliation(s)
- Jorge Duconge
- Department of Pharmaceutical SciencesSchool of PharmacyUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Ednalise Santiago
- Research Centers in Minority Institutions (RCMI) ProgramCenter for Collaborative Research in Health Disparities (CCRHD)Academic Affairs DeanshipUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Dagmar F. Hernandez‐Suarez
- Division of Cardiovascular MedicineSchool of MedicineUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Mariangeli Moneró
- Department of PharmacologySchool of MedicineUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Andrés López‐Reyes
- Department of BiologyCollege of Natural SciencesUniversity of Puerto Rico ‐ Rio Piedras CampusSan Juan, Puerto RicoUSA
| | - Marines Rosario
- Department of BiologyCollege of Natural SciencesUniversity of Puerto Rico ‐ Rio Piedras CampusSan Juan, Puerto RicoUSA
| | - Jessicca Y. Renta
- Research Centers in Minority Institutions (RCMI) ProgramCenter for Collaborative Research in Health Disparities (CCRHD)Academic Affairs DeanshipUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Pablo González
- Department of PharmacologySchool of MedicineUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | | | | | - Orlando Arce
- School of MedicineUniversidad Central del CaribeBayamon, Puerto RicoUSA
| | - Frances Marín‐Maldonado
- Research Centers in Minority Institutions (RCMI) ProgramCenter for Collaborative Research in Health Disparities (CCRHD)Academic Affairs DeanshipUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Héctor Nuñez
- Division of Cardiovascular MedicineSchool of MedicineUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Kyle Melin
- Department of Pharmacy PracticeSchool of PharmacyUniversity of Puerto Rico ‐ Medical Sciences CampusSan Juan, Puerto RicoUSA
| | - Stuart A. Scott
- Department of PathologyStanford UniversityPalo AltoCaliforniaUSA
| | - Gualberto Ruaño
- Institute of Living at Hartford HospitalHartfordConnecticutUSA
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Dai L, Xu J, Yan H, Chen Z, Pan Y, Meng X, Li H, Wang Y. Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial. Stroke 2021; 53:465-472. [PMID: 34666508 DOI: 10.1161/strokeaha.120.033049] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack. METHODS In this post-analysis of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), the ABCD-GENE score was calculated for all patients enrolled in this study. By using the proposed cutoff of 10, patients were stratified as being at high risk for high platelet reactivity or not. We further categorized the ABCD-GENE score to 0 to 5, 6 to 24, and >24 to investigate the cutoff value of this scale in clinical application. Stroke recurrence at 3 months was considered as the primary outcome. RESULTS Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCD-GENE score <10 and 650 (22.24%) patients with ABCD-GENE score ≥10. Compared with the aspirin alone, hazard ratios (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.70 (0.54-0.91) and 0.76 (0.46-1.24), among patients of ABCD-GENE scores <10 and ABCD-GENE scores ≥10, respectively. Stratified analyses by ABCD-GENE score 0 to 5, 6 to 24, and >24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38-0.85), 0.78 (0.58-1.06), and 1.20 (0.44-3.28) (P value for trend=0.0052). CONCLUSIONS Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.
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Affiliation(s)
- Liye Dai
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Jie Xu
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Hongyi Yan
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Zimo Chen
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Yuesong Pan
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Xia Meng
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Hao Li
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
| | - Yongjun Wang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.).,Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China. (L.D., J.X., H.Y., Z.C., Y.P., X.M., H.L., Y.W.)
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Wang J, Wang J, Dong Z, Ma J, Teng J, Wang T, Zhang X, Gu Q, Ye Z, Ullah I, Tan C, Abdus S, Shi L, Gong X, Li C. An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention. Thromb J 2021; 19:73. [PMID: 34666778 PMCID: PMC8527808 DOI: 10.1186/s12959-021-00323-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 09/21/2021] [Indexed: 11/10/2022] Open
Abstract
Objective This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI). Design A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding. Result 1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PLADP) 25.5–37.4%)] and outside the window group (OW) (PLADP < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54–0.89, P = 0.004)] than that in the OW group during 12-month follow-up. Conclusion An optimal therapeutic window of 25.5–37.4% for PLADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay. Trial registration Trial registration number: ClinicalTrials.govNCT01968499. Registered 18 October 2013 - Retrospectively registered.
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Affiliation(s)
- Jing Wang
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.,Department of Cardiology, the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
| | - Jing Wang
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Zhou Dong
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Jiazheng Ma
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Jianzhen Teng
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Tong Wang
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.,Department of Cardiology, the First People's Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Xiaofeng Zhang
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.,Department of Cardiology, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Qian Gu
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Zekang Ye
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Inam Ullah
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Chuchu Tan
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Samee Abdus
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Lu Shi
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Xiaoxuan Gong
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Chunjian Li
- Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
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Wan H, Han W, Wu Z, Lie Z, Li D, Su S. Whole blood dynamic platelet aggregation counting and 1-year clinical outcomes in patients with coronary heart diseases treated with clopidogrel. Platelets 2021; 32:968-974. [PMID: 32892681 DOI: 10.1080/09537104.2020.1817886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
In the setting of coronary heart diseases (CHDs) on treatment with clopidogrel, ADP-induced platelet aggregation has been demonstrated with ischemic events. However, there were very limited data for predicting ischemic events by platelet function test via dynamic platelet aggregation counting (DPAC). The present study aimed to evaluate the relationship between adenosine diphosphate (ADP)-induced whole blood platelet aggregation rates (PARs) and clinical outcomes in patients with CHDs on treatment with clopidogrel. We have retrospectively analyzed the clinical data of consecutive patients with CHDs based on the electronic medical records between May 2016 and December 2018. The primary endpoint was a composite endpoint events (CEEs) of ischemic cardiovascular events (including acute coronary syndrome, heart failure, transient ischemic attack, and cerebral infarction) and all-cause death. A total of 490 patients (mean age 66.6 years, 71% man) were received ADP-induced PARs via DPAC. On follow-up (mean 374 days), 107 subjects (21.8%) developed CEEs. Cox regression analysis indicated that the risk of CEEs was independently associated with ADP-induced whole blood PARs [HR: 1.023, 95% CI: 1.005-1.041, P = .011]. The distribution of CYP2C19 loss of function gene was higher in patients with on-treatment platelet hyperresponsiveness (10/12 vs 38/75, P = .042). In conclusion, ADP-induced whole blood PARs via DPAC is feasible, which can predict the incidence of 1-year CEEs in patients with CHDs on treatment with clopidogrel. CYP2C19 gene polymorphism was associated with clopidogrel on-treatment platelet hyperresponsiveness.
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Affiliation(s)
- Huaibin Wan
- Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
| | - Weichao Han
- Department of Pharmacy, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
| | - Zhihao Wu
- Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
| | - Zhenbang Lie
- Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
| | - Daqiang Li
- Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
| | - Shaohui Su
- Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China
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