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Akiyama R, Ishii A, Chihara H, Sakai C, Kikuchi T, Okawa M, Ikedo T, Takada S, Matsukawa S, Arakawa Y. Pipeline shield reduces diffusion-weighted imaging-detected ischemia after intracranial aneurysm treatment compared with pipeline flex: a propensity score-matched retrospective cohort study. J Neurointerv Surg 2025:jnis-2025-023229. [PMID: 40404297 DOI: 10.1136/jnis-2025-023229] [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: 02/07/2025] [Accepted: 05/11/2025] [Indexed: 05/24/2025]
Abstract
BACKGROUND The Pipeline Flex embolization device with Shield technology (PED Shield, Medtronic, Irvine, CA, USA) is a flow diverter designed to reduce thrombogenicity through phosphorylcholine surface modification. Although in vitro and in vivo studies have demonstrated the thrombogenicity reducing effects of this technology, its effectiveness in real-world clinical practice remains unclear. This study aims to compare the number of post-procedure diffusion-weighted imaging (DWI)-positive lesions between PED Flex(Medtronic, Irvine, CA, USA) and PED Shield to assess the impact of surface modification. METHODS This retrospective cohort study included patients with unruptured intracranial aneurysms treated with PED Flex or PED Shield between April 2016 and March 2024 at a single institution. Propensity score matching was performed to control for confounders, and the number of post-procedure DWI-positive lesions was evaluated as the primary outcome. RESULTS In total, 148 procedures (132 patients, 138 aneurysms) were included, with 68 (46%) treated with PED Flex and 80 (54%) with PED Shield. Propensity score matching resulted in 47 matched pairs. After matching, the median number of post-procedure DWI-positive lesions was nine (interquartile range (IQR): 3-17) in the PED Flex group and three (IQR: 1-6) in the PED Shield group, with a significantly lower number in the PED Shield group (regression coefficient β = -10.70 [95% confidence interval (CI): -16.23 to -5.16), P<0.001). CONCLUSION After adjusting for confounders, the PED Shield group had significantly fewer post-procedure DWI-positive lesions than the PED Flex group, suggesting that phosphorylcholine surface modification technology may reduce thrombogenicity in real-world clinical practice.
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Affiliation(s)
- Ryo Akiyama
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Akira Ishii
- Neurosugery, Juntendo University Hospital, Bunkyo-ku, Japan
| | - Hideo Chihara
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Chiaki Sakai
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Takayuki Kikuchi
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Masakazu Okawa
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Taichi Ikedo
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Shigeki Takada
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - So Matsukawa
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
| | - Yoshiki Arakawa
- Neurosurgery, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan
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Angiolillo DJ, Galli M, Alexopoulos D, Aradi D, Bhatt DL, Bonello L, Capodanno D, Cavallari LH, Collet JP, Cuisset T, Ferreiro JL, Franchi F, Geisler T, Gibson CM, Gorog DA, Gurbel PA, Jeong YH, Marcucci R, Siller-Matula JM, Mehran R, Neumann FJ, Pereira NL, Rizas KD, Rollini F, So DYF, Stone GW, Storey RF, Tantry US, Berg JT, Trenk D, Valgimigli M, Waksman R, Sibbing D. International Consensus Statement on Platelet Function and Genetic Testing in Percutaneous Coronary Intervention: 2024 Update. JACC Cardiovasc Interv 2024; 17:2639-2663. [PMID: 39603778 DOI: 10.1016/j.jcin.2024.08.027] [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: 07/03/2024] [Revised: 07/29/2024] [Accepted: 08/13/2024] [Indexed: 11/29/2024]
Abstract
Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient. However, bleeding and ischemic risks are often present in the same patient, making it difficult to achieve this balance. The fact that oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) have diverse pharmacodynamic profiles that affect clinical outcomes supports the rationale for using platelet function and genetic testing to individualize antiplatelet treatment regimens. Indeed, up to one-third of patients treated with clopidogrel, but a minority of those treated with prasugrel or ticagrelor, exhibit high residual platelet reactivity resulting in an increased thrombotic risk. On the other hand, prasugrel and ticagrelor are frequently associated with low platelet reactivity and increased bleeding risk compared with clopidogrel without providing any additional reduction in ischemic events compared with patients who adequately respond to clopidogrel. The use of platelet function and genetic testing may allow for a guided selection of oral P2Y12 inhibitors. However, the nonuniform results of randomized controlled trials have led guidelines to provide limited recommendations on the implementation of these tests in patients undergoing percutaneous coronary intervention. In light of recent advancements in the field, this consensus document by a panel of international experts fills in the guideline gap by providing updates on the latest evidence in the field as well as recommendations for clinical practice.
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Affiliation(s)
- Dominick J Angiolillo
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA.
| | - Mattia Galli
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
| | - Dimitrios Alexopoulos
- 7th Department of Cardiology, Hygeia Hospital, Athens, Greece; State Hospital for Cardiology, Balatonfüred, Hungary
| | - Daniel Aradi
- State Hospital for Cardiology, Balatonfüred, Hungary; Hungary and Heart and Vascular Centre, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Deepak L Bhatt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Laurent Bonello
- Intensive Care Unit, Hopital Universitaire Nord, Aix-Marseille University, Marseille, France
| | - Davide Capodanno
- Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco, University of Catania, Catania, Italy
| | - Larisa H Cavallari
- Center for Pharmacogenomics and Precision Medicine, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA
| | - Jean-Philippe Collet
- ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Thomas Cuisset
- Department of Cardiology, La Timone Hospital, Marseille, France
| | - Jose Luis Ferreiro
- Department of Cardiology, Joan XXIII University Hospital, IISPV, Rovira i Virgili University, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Tarragona, Spain
| | - Francesco Franchi
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Tobias Geisler
- Department of Cardiology and Angiology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - C Michael Gibson
- Baim Institute of Clinical Research, Harvard Medical School, Harvard University, Boston, Massachusetts, USA
| | - Diana A Gorog
- Cardiovascular Division, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom; Centre for Health Services and Clinical Research, Postgraduate Medical School, University of Hertfordshire, Hertfordshire, United Kingdom
| | - Paul A Gurbel
- Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland, USA
| | - Young-Hoon Jeong
- CAU Thrombosis and Biomarker Center, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea; Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Rossella Marcucci
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Jolanta M Siller-Matula
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Roxana Mehran
- Center for Interventional Cardiovascular Research and Clinical Trials, Icahn School Medicine at Mount Sinai, New York, New York, USA
| | - Franz-Josef Neumann
- Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Naveen L Pereira
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA
| | - Konstantinos D Rizas
- Medizinische Klinik und Poliklinik I, University Hospital Munich, Ludwig-Maximilians University, Munich, Germany; German Center for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany
| | - Fabiana Rollini
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Derek Y F So
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Gregg W Stone
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Robert F Storey
- Cardiovascular Research Unit, Division of Clinical Medicine, University of Sheffield, Sheffield, United Kingdom
| | - Udaya S Tantry
- Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland, USA
| | - Jurrien Ten Berg
- Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Cardiology, University Medical Center Maastricht, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
| | - Dietmar Trenk
- Clinical Pharmacology, Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marco Valgimigli
- Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland; Department of Biomedical Sciences, University of Italian Switzerland, Lugano, Switzerland; University of Bern, Bern, Switzerland
| | - Ron Waksman
- MedStar Heart & Vascular Institute, MedStar Washington Hospital Center, MedStar Georgetown University Hospital, Washington, DC, USA
| | - Dirk Sibbing
- Medizinische Klinik und Poliklinik I, University Hospital Munich, Ludwig-Maximilians University, Munich, Germany; Privatklinik Lauterbacher Mühle am Ostsee, Seeshaupt, Germany
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Elserwey A, Jabbour RJ, Curzen N. Does one size really fit all? The case for personalized antiplatelet therapy in interventional cardiology. Future Cardiol 2024; 20:499-515. [PMID: 39093436 PMCID: PMC11485715 DOI: 10.1080/14796678.2024.2384217] [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: 03/06/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024] Open
Abstract
Cardiovascular disease is the leading cause of death worldwide. Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor, is currently recommended as a default for patients after acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). However, controversies arise over the role of aspirin, the optimal duration of DAPT after drug-eluting stent (DES) implantation, the choice of P2Y12 inhibitor and the variability in individual responses to antiplatelet agents. Recent data indicate that monotherapy with a P2Y12 inhibitor may have adequate anti-ischemic effects with lower bleeding risk. Additionally, discrepancies in DAPT duration recommendations and the optimal P2Y12 inhibitor, provides more uncertainty. We ask the question "does one size really fits all?" or should a more personalized strategy should be implemented.
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Affiliation(s)
- Ahmed Elserwey
- Faculty of Medicine, University of Southampton
- University Hospital Southampton NHS FT
| | | | - Nick Curzen
- Faculty of Medicine, University of Southampton
- University Hospital Southampton NHS FT
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Plakogiannis FA, Weidmann J, Fraser B, Kwong J, Asi D, Kumar P, Baldock M, Naamo J, Baluja R, Catanzariti R, Yeung S, Pont L, Williams K, De Rubis G, Dua K, Bukhari NI. Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the smoker's paradox. Pathol Res Pract 2024; 257:155290. [PMID: 38640781 DOI: 10.1016/j.prp.2024.155290] [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: 02/08/2024] [Revised: 03/20/2024] [Accepted: 04/02/2024] [Indexed: 04/21/2024]
Abstract
The intricate relationship between smoking and the effects of the antiplatelet drug clopidogrel has been termed the "smoker's paradox". This paradox details the enhanced efficacy of clopidogrel in smokers compared to non-smokers. This review begins with an exploration of the proposed mechanisms of the smoker's paradox, particularly drawing attention to the induction of cytochrome P450 (CYP) isoenzymes via tobacco smoke, specifically the enzymes CYP1A2 and CYP2C19. Moreover, an investigation of the effects of genetic variability on the smoker's paradox was undertaken from both clinical and molecular perspectives, delving into the effects of ethnicity and genetic polymorphisms. The intriguing role of CYP1A2 genotypes and the response to clopidogrel in smoking and non-smoking populations was examined conferring insight into the individuality rather than universality of the smoker's paradox. CYP1A2 induction is hypothesised to elucidate the potency of smoking in exerting a counteracting effect in those taking clopidogrel who possess CYP2C19 loss of function polymorphisms. Furthermore, we assess the comparative efficacies of clopidogrel and other antiplatelet agents, namely prasugrel and ticagrelor. Studies indicated that prasugrel and ticagrelor provided a more consistent effect and further reduced platelet reactivity compared to clopidogrel within both smoking and non-smoking populations. Personalised dosing was another focus of the review considering patient comorbidities, genetic makeup, and smoking status with the objective of improving the antiplatelet response of those taking clopidogrel. In summation, this review provides insight into multiple areas of research concerning clopidogrel and the smoker's paradox taking into account proposed mechanisms, genetics, other antiplatelet agents, and personalised dosing.
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Affiliation(s)
- Frank A Plakogiannis
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Jakob Weidmann
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Blake Fraser
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Justin Kwong
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Diana Asi
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Pratham Kumar
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Madeleine Baldock
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Jasmine Naamo
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Ruhani Baluja
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Rachelle Catanzariti
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Stewart Yeung
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia
| | - Lisa Pont
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Kylie Williams
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Gabriele De Rubis
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia.
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia.
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Ahn H, Chu HW, Her AY, Jeong YH, Kim BK, Joo HJ, Chang K, Park Y, Ahn SG, Lee SY, Cho JR, Kim HS, Kim MH, Lim DS, Shin ES, Suh JW. Effect of Calcium Channel Blockers on Antiplatelet Activity of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: Insights from the PTRG-DES Consortium. J Cardiovasc Pharmacol Ther 2024; 29:10742484241298150. [PMID: 39552592 DOI: 10.1177/10742484241298150] [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] [Indexed: 11/19/2024]
Abstract
Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P = .156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P-value .663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P-value .262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028.
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Affiliation(s)
- HoungBeom Ahn
- Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyun-Wook Chu
- Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Cardiology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Ae-Young Her
- Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Young-Hoon Jeong
- CAU Thrombosis and Biomarker Center, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Byeong-Keuk Kim
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyung Joon Joo
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Kiyuk Chang
- Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yongwhi Park
- Division of Cardiology, Department of Medicine, Gyeongsang National University School of Medicine, Changwon, South Korea
| | - Sung Gyun Ahn
- Department of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea
| | - Sang Yeup Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea
- Division of Cardiology, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea
| | - Jung Rae Cho
- Cardiology Division, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Hyo-Soo Kim
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea
| | - Moo Hyun Kim
- Department of Cardiology, Dong-A University Hospital, Busan, South Korea
| | - Do-Sun Lim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Eun-Seok Shin
- Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Jung-Won Suh
- Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
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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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Chyrchel B, Kruszelnicka O, Wieczorek-Surdacka E, Surdacki A. Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy. J Clin Med 2023; 12:4530. [PMID: 37445565 DOI: 10.3390/jcm12134530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/28/2023] [Accepted: 07/05/2023] [Indexed: 07/15/2023] Open
Abstract
The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190-460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies.
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Affiliation(s)
- Bernadeta Chyrchel
- Second Department of Cardiology, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland
- Department of Cardiology and Cardiovascular Interventions, University Hospital, 2 Jakubowskiego Street, 30-688 Cracow, Poland
| | - Olga Kruszelnicka
- Department of Coronary Artery Disease and Heart Failure, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 80 Prądnicka Street, 31-202 Cracow, Poland
| | - Ewa Wieczorek-Surdacka
- Center of Innovative Medical Education, Jagiellonian University Medical College, 7 Medyczna Street, 30-688 Cracow, Poland
| | - Andrzej Surdacki
- Second Department of Cardiology, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland
- Department of Cardiology and Cardiovascular Interventions, University Hospital, 2 Jakubowskiego Street, 30-688 Cracow, Poland
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8
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Perla HT, Thomson VS, Attumalil TV, Geevar T, Alex AG, Dave RG, Nair SC, Gowri SM, Mony PK, George P, Joseph G. Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome. Am J Cardiovasc Drugs 2023:10.1007/s40256-023-00591-8. [PMID: 37351814 DOI: 10.1007/s40256-023-00591-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/22/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.
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Affiliation(s)
- Harsha Teja Perla
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India
| | - Viji Samuel Thomson
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India.
- Salalah Heart Center, Salalah, Oman.
| | - Thomas V Attumalil
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India
| | - Tulasi Geevar
- Department of Immunohematology and Transfusion Medicine, Christian Medical College and Hospital, Vellore, India
| | - Anoop George Alex
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India
| | - Rutvi G Dave
- Department of Immunohematology and Transfusion Medicine, Christian Medical College and Hospital, Vellore, India
| | - Sukesh C Nair
- Department of Immunohematology and Transfusion Medicine, Christian Medical College and Hospital, Vellore, India
| | - S Mahasampath Gowri
- Department of Biostatistics, Christian Medical College and Hospital, Vellore, India
| | - Prem K Mony
- Department of Epidemiology and Population Health, St John's National Academy of Health Sciences, Bangalore, India
| | - Paul George
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India
| | - George Joseph
- Department of Cardiology, Christian Medical College and Hospital, Vellore, India
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Karwatowska-Prokopczuk E, Li L, Yang J, Witztum JL, Tsimikas S. On-treatment platelet reactivity through the thromboxane A 2 or P2Y12 platelet receptor pathways is not affected by pelacarsen. J Thromb Thrombolysis 2023:10.1007/s11239-023-02818-6. [PMID: 37338713 DOI: 10.1007/s11239-023-02818-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/14/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND Pelacarsen decreases plasma levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPL). It was previously reported that pelacarsen does not affect the platelet count. We now report the effect of pelacarsen on on-treatment platelet reactivity. METHODS Subjects with established cardiovascular disease and screening Lp(a) levels ≥60 mg per deciliter (~ ≥150 nmol/L) were randomized to receive pelacarsen (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or placebo for 6-12 months. Aspirin Reaction Units (ARU) and P2Y12 Reaction Units (PRU) were measured at baseline and the primary analysis timepoint (PAT) at 6 months. RESULTS Of the 286 subjects randomized, 275 had either an ARU or PRU test, 159 (57.8%) were on aspirin alone and 94 (34.2%) subjects were on dual anti-platelet therapy. As expected, the baseline ARU and PRU were suppressed in subjects on aspirin or on dual anti-platelet therapy, respectively. There were no significant differences in baseline ARU in the aspirin groups or in PRU in the dual anti-platelet groups. At the PAT there were no statistically significant differences in ARU in subjects on aspirin or PRU in subjects on dual anti-platelet therapy among any of the pelacarsen groups compared to the pooled placebo group (p > 0.05 for all comparisons). CONCLUSION Pelacarsen does not modify on-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways.
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Affiliation(s)
| | - Lu Li
- Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA
| | - Jun Yang
- Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA
| | | | - Sotirios Tsimikas
- Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA.
- Vascular Medicine Program, Sulpizio Cardiovascular Center, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA, 92093-0682, USA.
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10
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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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Kim S, Her A, Jeong Y, Kim B, Joo HJ, Park Y, Chang K, Song YB, Ahn SG, Suh J, Lee SY, Cho JR, Kim H, Kim MH, Lim D, Shin E, PTRG‐DES Consortium Investigators. Sex Differences in Midterm Prognostic Implications of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents in East Asian Patients: Results From the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium. J Am Heart Assoc 2023; 12:e027804. [PMID: 37119080 PMCID: PMC10227230 DOI: 10.1161/jaha.122.027804] [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: 08/12/2022] [Accepted: 01/18/2023] [Indexed: 04/30/2023]
Abstract
Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug-eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all-cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity-adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20-2.12]; women with HPR: HR, 0.99 [95% CI, 0.69-1.42]) and all-cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07-2.44]; women with HPR: HR, 0.92 [95% CI, 0.57-1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (Pinteraction=0.013) or all-cause mortality (Pinteraction=0.025). Conclusions In this study, HPR was a differential risk factor for 1-year MACCEs and all-cause mortality in women and men. And it was an independent predictor of 1-year MACCEs and all-cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028.
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Affiliation(s)
- Soo‐Jin Kim
- Division of Cardiology, Department of Internal MedicineKosin University College of MedicineBusanSouth Korea
| | - Ae‐Young Her
- Division of Cardiology, Department of Internal MedicineKangwon National University School of MedicineChuncheonSouth Korea
| | - Young‐Hoon Jeong
- Chung‐Ang University Thrombosis CenterGwangmyeong Chung‐Ang University Medical CenterGwangmyeongSouth Korea
| | - Byeong‐Keuk Kim
- Severance Cardiovascular HospitalYonsei University College of MedicineSeoulSouth Korea
| | - Hyung Joon Joo
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
| | - Yongwhi Park
- Department of Internal MedicineGyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon HospitalChangwonSouth Korea
| | - Kiyuk Chang
- Division of Cardiology, Department of Internal MedicineCollege of Medicine, Catholic University of KoreaSeoulSouth 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 Internal MedicineSeoul National University College of Medicine and Department of Cardiology, Seoul National University Bundang HospitalSeongnamSouth Korea
| | - Sang Yeub Lee
- Division of Cardiology, Department of Internal MedicineChungbuk National University, College of MedicineCheongjuSouth Korea
| | - Jung Rae Cho
- Cardiology Division, Department of Internal MedicineKangnam Sacred Heart Hospital, Hallym University College of MedicineSeoulSouth 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
| | - Do‐Sun Lim
- Department of Cardiology, Cardiovascular CenterKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
| | - Eun‐Seok Shin
- Department of CardiologyUlsan University Hospital, University of Ulsan College of MedicineUlsanSouth Korea
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12
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Giantini A, Timan IS, Dharma R, Sukmawan R, Setiabudy R, Alwi I, Harahap AR, Listiyaningsih E, Partakusuma LG, Tansir AR, Sahar W, Hidayat R. The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention. Front Cardiovasc Med 2023; 9:1027892. [PMID: 36843628 PMCID: PMC9944402 DOI: 10.3389/fcvm.2022.1027892] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 12/30/2022] [Indexed: 02/11/2023] Open
Abstract
Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.
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Affiliation(s)
- Astuti Giantini
- Clinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia,Universitas Indonesia Hospital, Universitas Indonesia, Depok, Indonesia,*Correspondence: Astuti Giantini ✉
| | - Ina S. Timan
- Clinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
| | - Rahajuningsih Dharma
- Clinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
| | - Renan Sukmawan
- Cardiology and Vascular Medicine Department, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Center Harapan Kita, West Jakarta, Indonesia
| | - Rianto Setiabudy
- Pharmacology and Therapeutics Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
| | - Idrus Alwi
- Internal Medicine Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
| | - Alida R. Harahap
- Clinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
| | | | | | - Arif R. Tansir
- Faculty of Medicine, Universitas Indonesia, Central Jakarta, Indonesia
| | - Windy Sahar
- Universitas Indonesia Hospital, Universitas Indonesia, Depok, Indonesia
| | - Rakhmad Hidayat
- Universitas Indonesia Hospital, Universitas Indonesia, Depok, Indonesia,Neurology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, Indonesia
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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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Djordjevic N. Genotyping genetic variants of CYP2C19 for precision antiplatelet dosing: state of the art and future perspectives. Expert Opin Drug Metab Toxicol 2022; 18:817-830. [PMID: 36606363 DOI: 10.1080/17425255.2022.2166486] [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: 01/07/2023]
Abstract
INTRODUCTION Clopidogrel is the only antiplatelet agent whose activity is significantly affected by CYP2C19 polymorphism. AREAS COVERED This review has summarized the available evidence on the clinically significant association between CYP2C19 polymorphism and clopidogrel-based therapy; reviewed the current recommendations for clinical use of CYP2C19 genotype test results in patients on clopidogrel treatment; and discussed possible pitfalls of routine application, and future perspectives of antiplatelets pharmacogenetics. EXPERT OPINION The available body of evidence, reflected in several meta-analyses and high-quality clinical practice guidelines, shows that the presence of CYP2C19 LOF alleles, especially CYP2C19*2, correlates with impaired activation of clopidogrel and variable platelet inhibition, followed by minimal or no antiplatelet effect, and higher risk of treatment failure. In combination with other known risk factors, CYP2C19 genetic testing could be very valuable in predicting low clopidogrel efficacy. At the same time, it could be very successful in selecting patients who will most probably benefit from the clopidogrel-based therapy, thus decreasing the pool of those who might need more expensive and otherwise riskier antiplatelet alternatives.
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Affiliation(s)
- Natasa Djordjevic
- Faculty of Medical Sciences, Department of Pharmacology and Toxicology, University of Kragujevac, Svetozara Markovica 69, 34 000 Kragujevac, Serbia
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Gurbel PA, Navarese EP, Myat A, Tantry US. Peri‐procedural Platelet Function Testing in Risk Stratification and Clinical Decision Making. Interv Cardiol 2022. [DOI: 10.1002/9781119697367.ch45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Xie Q, Xiang Q, Liu Z, Mu G, Zhou S, Zhang Z, Ma L, Gong Y, Jiang J, Cui Y. Effect of CYP2C19 genetic polymorphism on the pharmacodynamics and clinical outcomes for patients treated with ticagrelor: a systematic review with qualitative and quantitative meta-analysis. BMC Cardiovasc Disord 2022; 22:111. [PMID: 35300607 PMCID: PMC8928616 DOI: 10.1186/s12872-022-02547-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/04/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Studies show inconsistent results regarding the impact of CYP2C19 genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of genotype-guided individualized antiplatelet therapy, the association between CYP2C19 polymorphism and the efficacy and safety of ticagrelor for patients is still worthy of exploring and studying. METHODS This systematic review protocol has been registered in the PROSPERO network (No. CRD 42020158920). Electronic databases of PubMed, EmBase, and the Cochrane Library were systematically searched from inception to January 6th, 2022 to select studies investigating the impact of CYP2C19 genotype on PD and clinical outcomes of ticagrelor. The results were presented as odds ratio (OR) or weight mean difference with its 95% confidence interval (CI) by using the random-effects model. Trial sequential analysis (TSA) was used to control risk of random errors and detect the robustness of outcomes. RESULTS Eight studies recruited a total of 6405 patients treated with ticagrelor. Mostly trials reported no significant effect of any or no CYP2C19 loss-of-function (LOF) allele (*2 or *3) on all the endpoints. Compared with no LOF allele carriers, subgroup analysis suggested any LOF allele in Asian patients was associated with a significant decreased risk of bleeding events (OR: 0.41; 95% CI: 0.22-0.75; P = 0.004). Furthermore, any LOF allele carriers didn't yield any impact on the risk of MACEs (OR: 1.11; 95% CI: 0.76-1.64; P = 0.586), stroke (OR: 1.71; 95% CI: 0.99-2.96; P = 0.054), definite stent thrombosis (OR: 0.88; 95% CI: 0.17-4.60; P = 0.882), bleeding (OR: 0.63; 95% CI: 0.27-1.46; P = 0.281), myocardial infarction (OR: 0.81; 95% CI: 0.30-2.20; P = 0.682), and revascularization (OR: 0.81; 95% CI: 0.33-2.00; P = 0.649) in all patients. The results of TSA were indicated that more further trials would be required. CONCLUSIONS This qualitative and quantitative study suggested Asian patients carrying any CYP2C19 LOF allele might have a lower risk of bleeding events comparing with no LOF allele carriers when treated with ticagrelor. However, we did not prove an important role of CYP2C19 genotype on the risk of PD and clinical endpoints in the whole cohort. In future, more large-scale prospective studies and more different ethnic populations should be included.
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Affiliation(s)
- Qiufen Xie
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Qian Xiang
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Zhiyan Liu
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Guangyan Mu
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Shuang Zhou
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Zhuo Zhang
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Lingyue Ma
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China
| | - Yanjun Gong
- Department of Cardiology, Peking University First Hospital, No. 8, Xi Shi Ku Street, Beijing, 100034, China
| | - Jie Jiang
- Department of Cardiology, Peking University First Hospital, No. 8, Xi Shi Ku Street, Beijing, 100034, China.
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China.
- Institue of Clinical Pharmacology, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, 100191, China.
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Yeh CH, Chou YJ, Tsai TH, Hsu PWC, Li CH, Chan YH, Tsai SF, Ng SC, Chou KM, Lin YC, Juan YH, Fu TC, Lai CC, Sytwu HK, Tsai TF. Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease. Biomedicines 2022; 10:biomedicines10010116. [PMID: 35052795 PMCID: PMC8773099 DOI: 10.3390/biomedicines10010116] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/30/2021] [Accepted: 01/04/2022] [Indexed: 12/15/2022] Open
Abstract
An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.
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Affiliation(s)
- Chi-Hsiao Yeh
- Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (Y.-C.L.); (Y.-H.J.); (T.-C.F.)
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Yi-Ju Chou
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan; (Y.-J.C.); (P.W.-C.H.); (S.-F.T.)
| | - Tsung-Hsien Tsai
- Advanced Tech BU, Acer Inc., New Taipei City 221, Taiwan; (T.-H.T.); (C.-H.L.); (Y.-H.C.)
| | - Paul Wei-Che Hsu
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan; (Y.-J.C.); (P.W.-C.H.); (S.-F.T.)
| | - Chun-Hsien Li
- Advanced Tech BU, Acer Inc., New Taipei City 221, Taiwan; (T.-H.T.); (C.-H.L.); (Y.-H.C.)
| | - Yun-Hsuan Chan
- Advanced Tech BU, Acer Inc., New Taipei City 221, Taiwan; (T.-H.T.); (C.-H.L.); (Y.-H.C.)
| | - Shih-Feng Tsai
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan; (Y.-J.C.); (P.W.-C.H.); (S.-F.T.)
| | - Soh-Ching Ng
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.N.); (K.-M.C.)
| | - Kuei-Mei Chou
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.N.); (K.-M.C.)
| | - Yu-Ching Lin
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (Y.-C.L.); (Y.-H.J.); (T.-C.F.)
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Yu-Hsiang Juan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (Y.-C.L.); (Y.-H.J.); (T.-C.F.)
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Tieh-Cheng Fu
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (Y.-C.L.); (Y.-H.J.); (T.-C.F.)
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Chi-Chun Lai
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (Y.-C.L.); (Y.-H.J.); (T.-C.F.)
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Correspondence: (C.-C.L.); (H.-K.S.); (T.-F.T.); Tel.: +886-2-24313131 (ext. 6101) (C.-C.L.); +886-37-206166 (ext. 31010) (H.-K.S.); +886-2-28267293 (T.-F.T.)
| | - Huey-Kang Sytwu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan
- National Defense Medical Center, Department & Graduate Institute of Microbiology and Immunology, Taipei 114, Taiwan
- Correspondence: (C.-C.L.); (H.-K.S.); (T.-F.T.); Tel.: +886-2-24313131 (ext. 6101) (C.-C.L.); +886-37-206166 (ext. 31010) (H.-K.S.); +886-2-28267293 (T.-F.T.)
| | - Ting-Fen Tsai
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan; (Y.-J.C.); (P.W.-C.H.); (S.-F.T.)
- Departments of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Correspondence: (C.-C.L.); (H.-K.S.); (T.-F.T.); Tel.: +886-2-24313131 (ext. 6101) (C.-C.L.); +886-37-206166 (ext. 31010) (H.-K.S.); +886-2-28267293 (T.-F.T.)
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18
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Malik AH, Gupta R, Chakraborty S, Mahajan P, Bandyopadhyay D, Yandrapalli S, Zaid S, Sreenivasan J, Chaturvedi A, Mehta SS, Vyas AV, Patel NC, Combs WG, Ahmad H. Effect of genotype guided oral P2Y12 inhibitor selection after percutaneous coronary intervention: A systematic review and meta-analysis of randomized clinical trials. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2022; 41:115-121. [DOI: 10.1016/j.carrev.2022.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 12/11/2021] [Accepted: 01/06/2022] [Indexed: 11/25/2022]
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19
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Collette SL, Bokkers RPH, Dierckx RAJO, van der Laan MJ, Zeebregts CJ, Uyttenboogaart M. Clinical importance of testing for clopidogrel resistance in patients undergoing carotid artery stenting-a systematic review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1211. [PMID: 34430652 PMCID: PMC8350701 DOI: 10.21037/atm-20-7153] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/04/2021] [Indexed: 12/04/2022]
Abstract
Dual antiplatelet therapy is frequently prescribed for patients undergoing carotid artery stenting (CAS), however clopidogrel resistance might cause thromboembolic complications. The role of testing for clopidogrel resistance in patients undergoing CAS is unclear. In this study, we aimed to review the periprocedural thromboembolic outcomes in clopidogrel resistant patients who underwent CAS. We conducted a review of PubMed, EMBASE, and the Cochrane Library up to October 7, 2020. Studies were included that investigated at least ten patients aged 18 years or older with a symptomatic carotid artery stenosis requiring CAS. Studies were excluded that investigated patients with a carotid artery dissection, case reports, case series of less than ten patients, reviews, commentaries, letters to the editors, and conference abstracts. The primary endpoint was the incidence of thromboembolic events. One hundred seventy-seven unique articles were identified of which three studies were included in our systematic review. The sample sizes ranged from 76 to 449 patients and the follow-up duration from 24 hours to 2 years postprocedural. Two retrospective observational studies determined clopidogrel resistance using measurement of P2Y12 reaction units, and one historical cohort study used genetic testing. Two studies concluded that clopidogrel resistance was a risk factor for thromboembolic complications, the other found higher values of P2Y12 reaction units in patients with thromboembolic events compared to those without. In conclusion, current literature supports a possible relationship between clopidogrel resistance and thromboembolic complications in patients who underwent CAS. Preprocedural testing for clopidogrel resistance might therefore be of additional value. Randomized studies using a valid, reliable clopidogrel resistance test and clinical endpoints, are however required to make a definitive statement and to determine the impact of the thromboembolic complications. This study was registered within PROSPERO (CRD42020197318).
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Affiliation(s)
- Sabine L Collette
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Reinoud P H Bokkers
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Rudi A J O Dierckx
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Maarten J van der Laan
- Division of Vascular Surgery, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Clark J Zeebregts
- Division of Vascular Surgery, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Maarten Uyttenboogaart
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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20
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Mshelbwala FS, Hugenberg DW, Kreutz RP. Intensified P2Y12 inhibition for high-on treatment platelet reactivity. J Thromb Thrombolysis 2021; 50:619-627. [PMID: 32152791 DOI: 10.1007/s11239-020-02075-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
High on treatment platelet reactivity (HPR) during treatment with clopidogrel has been consistently found to be strong risk factor for recurrent ischemic events after percutaneous coronary intervention (PCI). Insufficient P2Y12 receptor inhibition contributes to HPR measured by the VerifyNow (VN) assay. Prasugrel and ticagrelor are more potent P2Y12 inhibitors than clopidogrel and commonly substituted for clopidogrel when HPR is documented, however benefit of VN guided intensified antiplatelet therapy is uncertain. We identified patients who had undergone platelet reactivity testing after PCI with VN after pretreatment with clopidogrel (n = 252) in a single center observational analysis. Patients who had HPR defined as PRU > 208 were switched to alternate P2Y12 inhibitors. Primary clinical endpoint was 1-year post PCI combined cardiovascular death, myocardial infarction (MI), and stent thrombosis. One hundred and eight (43%) subjects had HPR and were switched to prasugrel (n = 60) and ticagrelor (n = 48). Risk of recurrent 1-year primary endpoint remained higher for HPR patients switched to either ticagrelor or prasugrel as compared to subjects who had low on treatment platelet reactivity (n = 144) (LPR) on clopidogrel [Hazard Ratio: 3.5 (95% CI 1.1-11.1); p = 0.036)]. Propensity score matched analysis demonstrated higher event rates in patients with HPR on alternate P2Y12 inhibitor as compared to patients with LPR (log-rank: p = 0.044). The increased risk of recurrent events associated with HPR measured by VN is not completely attenuated by switching to more potent P2Y12 inhibitors. Non-P2Y12 mediated pathways likely contribute to increased incidence of thrombotic events after PCI in subjects with HPR.
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Affiliation(s)
- Fakilahyel S Mshelbwala
- Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Daniel W Hugenberg
- Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Rolf P Kreutz
- Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
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21
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Nicolau JC, Feitosa Filho GS, Petriz JL, Furtado RHDM, Précoma DB, Lemke W, Lopes RD, Timerman A, Marin Neto JA, Bezerra Neto L, Gomes BFDO, Santos ECL, Piegas LS, Soeiro ADM, Negri AJDA, Franci A, Markman Filho B, Baccaro BM, Montenegro CEL, Rochitte CE, Barbosa CJDG, Virgens CMBD, Stefanini E, Manenti ERF, Lima FG, Monteiro Júnior FDC, Correa Filho H, Pena HPM, Pinto IMF, Falcão JLDAA, Sena JP, Peixoto JM, Souza JAD, Silva LSD, Maia LN, Ohe LN, Baracioli LM, Dallan LADO, Dallan LAP, Mattos LAPE, Bodanese LC, Ritt LEF, Canesin MF, Rivas MBDS, Franken M, Magalhães MJG, Oliveira Júnior MTD, Filgueiras Filho NM, Dutra OP, Coelho OR, Leães PE, Rossi PRF, Soares PR, Lemos Neto PA, Farsky PS, Cavalcanti RRC, Alves RJ, Kalil RAK, Esporcatte R, Marino RL, Giraldez RRCV, Meneghelo RS, Lima RDSL, Ramos RF, Falcão SNDRS, Dalçóquio TF, Lemke VDMG, Chalela WA, Mathias Júnior W. Brazilian Society of Cardiology Guidelines on Unstable Angina and Acute Myocardial Infarction without ST-Segment Elevation - 2021. Arq Bras Cardiol 2021; 117:181-264. [PMID: 34320090 PMCID: PMC8294740 DOI: 10.36660/abc.20210180] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- José Carlos Nicolau
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Gilson Soares Feitosa Filho
- Escola Bahiana de Medicina e Saúde Pública, Salvador, BA - Brasil
- Centro Universitário de Tecnologia e Ciência (UniFTC), Salvador, BA - Brasil
| | - João Luiz Petriz
- Hospital Barra D'Or, Rede D'Or São Luiz, Rio de Janeiro, RJ - Brasil
| | | | | | - Walmor Lemke
- Clínica Cardiocare, Curitiba, PR - Brasil
- Hospital das Nações, Curitiba, PR - Brasil
| | | | - Ari Timerman
- Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brasil
| | - José A Marin Neto
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Ribeirão Preto, SP - Brasil
| | | | - Bruno Ferraz de Oliveira Gomes
- Hospital Barra D'Or, Rede D'Or São Luiz, Rio de Janeiro, RJ - Brasil
- Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ - Brasil
| | | | | | | | | | | | | | | | | | - Carlos Eduardo Rochitte
- Hospital do Coração (HCor), São Paulo, SP - Brasil
- Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | - Edson Stefanini
- Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP), São Paulo, SP - Brasil
| | | | - Felipe Gallego Lima
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | | | | | | | | | - José Maria Peixoto
- Universidade José do Rosário Vellano (UNIFENAS), Belo Horizonte, MG - Brasil
| | - Juliana Ascenção de Souza
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | - Lilia Nigro Maia
- Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP - Brasil
| | | | - Luciano Moreira Baracioli
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Luís Alberto de Oliveira Dallan
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Luis Augusto Palma Dallan
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | - Luiz Carlos Bodanese
- Pontifícia Universidade Católica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS - Brasil
| | | | | | - Marcelo Bueno da Silva Rivas
- Rede D'Or São Luiz, Rio de Janeiro, RJ - Brasil
- Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brasil
| | | | | | - Múcio Tavares de Oliveira Júnior
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Nivaldo Menezes Filgueiras Filho
- Universidade do Estado da Bahia (UNEB), Salvador, BA - Brasil
- Universidade Salvador (UNIFACS), Salvador, BA - Brasil
- Hospital EMEC, Salvador, BA - Brasil
| | - Oscar Pereira Dutra
- Instituto de Cardiologia - Fundação Universitária de Cardiologia do Rio Grande do Sul, Porto Alegre, RS - Brasil
| | - Otávio Rizzi Coelho
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brasil
| | | | | | - Paulo Rogério Soares
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | | | | | | | - Roberto Esporcatte
- Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brasil
| | | | | | | | | | | | | | - Talia Falcão Dalçóquio
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | - William Azem Chalela
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Wilson Mathias Júnior
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
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22
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Li X, Yao Q, Cui H, Yang J, Wu N, Liu Y, Zhou Y, Zhang Y, Su J, Xia Y, Chen X. MiR-223 or miR-126 predicts resistance to dual antiplatelet therapy in patients with ST-elevation myocardial infarction. J Int Med Res 2021; 49:3000605211016209. [PMID: 34098766 PMCID: PMC8191085 DOI: 10.1177/03000605211016209] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective To explore the role of miR-223 and miR-126 in predicting treatment responses to dual antiplatelet therapy (DAPT) in patients with ST-elevation myocardial infarction (STEMI). Methods Plasma miR-223 and miR-126 levels were measured before treatment. Treatment responses and 2-year survival were determined. In vitro experiments were performed to explore the mechanism of action. Results Patients with resistance to DAPT had a lower level of miR-223 and miR-126. Cardiac-event-free survival was shorter in patients with lower miR-223 or miR-126 levels. MiR-223 and miR-126 independently predicted DAPT resistance. Modulating miR-223 or miR-126 in platelets in vitro significantly changed the response to clopidogrel by regulating platelet aggregation. Conclusion MiR-223 and miR-126 play a role in DAPT resistance and may provide potential biomarkers in patients with STEMI.
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Affiliation(s)
- Xiaojing Li
- Cardiovascular Center of Ningbo First Hospital, Ningbo, China
| | - Qi Yao
- Geriatric Medicine Center of Ningbo First Hospital, Ningbo, China
| | - Hanbin Cui
- Cardiovascular Center of Ningbo First Hospital, Ningbo, China
| | - Jun Yang
- Geriatric Medicine Center of Ningbo First Hospital, Ningbo, China
| | - Nan Wu
- Cardiovascular Center of Ningbo First Hospital, Ningbo, China
| | - Yahui Liu
- Key Laboratory of Ningbo First Hospital, Ningbo, China
| | - Ying Zhou
- Key Laboratory of Ningbo First Hospital, Ningbo, China
| | - Yinwei Zhang
- Geriatric Medicine Center of Ningbo First Hospital, Ningbo, China
| | - Jia Su
- Cardiovascular Center of Ningbo First Hospital, Ningbo, China
| | - Yezi Xia
- Geriatric Medicine Center of Ningbo First Hospital, Ningbo, China
| | - Xiaomin Chen
- Cardiovascular Center of Ningbo First Hospital, Ningbo, China
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23
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Hally KE, Parker OM, Brunton-O'Sullivan MM, Harding SA, Larsen PD. Linking Neutrophil Extracellular Traps and Platelet Activation: A Composite Biomarker Score for Predicting Outcomes after Acute Myocardial Infarction. Thromb Haemost 2021; 121:1637-1649. [PMID: 33984869 DOI: 10.1055/s-0041-1728763] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet-neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk. Investigating the combined effect of biomarkers for NETosis and platelet activation represents a novel approach to risk prediction post-AMI. Here, we examined the utility of a composite biomarker score, inclusive of both pathways, for predicting MACE post-AMI. METHODS AND RESULTS In a case-control design, 100 case patients who experienced MACE within 1 year of index admission were matched in a 1:2 ratio with control patients. Serum levels of myeloperoxidase-DNA, neutrophil elastase-DNA, and citrullinated histone H3 were assayed by enzyme-linked immunosorbent assay (ELISA) as markers of NET burden. To measure platelet activation, soluble P-selectin was assayed by ELISA in parallel. Platelet and neutrophil counts were also recorded. Composite biomarker scores, inclusive of biomarkers for NETosis and platelet activation, were assessed using multivariate regression modeling. These composite biomarker scores were independent predictors of 1-year MACE. The strongest association with MACE was observed using a composite of platelet count, soluble P-selectin, and all NET markers (odds ratio: 1.94; 1.16-3.25). CONCLUSION Here, we demonstrate the importance of combining biomarkers of NETosis and platelet activation for risk prediction in patients with AMI. Combining biomarkers from closely linked, but distinct, biological pathways was more effective than utilizing either type of biomarker alone.
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Affiliation(s)
- Kathryn E Hally
- Department of Surgery and Anaesthesia, The University of Otago, Wellington, New Zealand.,School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.,Wellington Cardiovascular Research Group, Wellington, New Zealand
| | - Olivia M Parker
- Department of Surgery and Anaesthesia, The University of Otago, Wellington, New Zealand.,Wellington Cardiovascular Research Group, Wellington, New Zealand
| | - Morgane M Brunton-O'Sullivan
- Department of Surgery and Anaesthesia, The University of Otago, Wellington, New Zealand.,Wellington Cardiovascular Research Group, Wellington, New Zealand
| | - Scott A Harding
- Wellington Cardiovascular Research Group, Wellington, New Zealand.,Department of Cardiology, Wellington Regional Hospital, Wellington, New Zealand
| | - Peter D Larsen
- Department of Surgery and Anaesthesia, The University of Otago, Wellington, New Zealand.,School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.,Wellington Cardiovascular Research Group, Wellington, New Zealand
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24
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Dias JD, Pottgiesser T, Hartmann J, Duerschmied D, Bode C, Achneck HE. Comparison of three common whole blood platelet function tests for in vitro P2Y12 induced platelet inhibition. J Thromb Thrombolysis 2021; 50:135-143. [PMID: 31620937 PMCID: PMC7293977 DOI: 10.1007/s11239-019-01971-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0–7500 ng/mL) and/or ASA (0–3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19–9153 ng/mL), followed by TEG®6s (144–2589 ng/mL), and VerifyNow® (191–1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.
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Affiliation(s)
| | - Torben Pottgiesser
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
| | | | - Daniel Duerschmied
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
| | - Christoph Bode
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
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Lin SF, Lin PC, Chang CC, Chang WL, Chu FY. Investigation of the interaction between proton pump inhibitors and clopidogrel using VerifyNow P2Y12 assay. Medicine (Baltimore) 2020; 99:e23695. [PMID: 33327360 PMCID: PMC7738015 DOI: 10.1097/md.0000000000023695] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/11/2020] [Accepted: 11/13/2020] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Randomized trials and observation studies have revealed conflicting results regarding the interaction between clopidogrel and proton pump inhibitors (PPIs). The aim of our study was to provide laboratory evidence regarding whether PPIs blunt the antiplatelet reactivity of clopidogrel. METHODS We included records of Asian patients who received clopidogrel treatment for cardiovascular or cerebrovascular events and the VerifyNow P2Y12 assay for platelet reactivity monitoring. The responsiveness of antiplatelet effect to clopidogrel was analyzed according to 3 criteria:Results: Patients treated without PPIs did not differ significantly from those concomitantly treated with PPIs in terms of levels of PI (25.7% ± 24.3% vs 23.0 ± 25.3%, P = .4315), PRU (187.3 ± 74.0 vs 197.4 ± 77.3, P = .3373), or responsiveness to antiplatelet (adjusted absolute risk, 3.5%; 95% confidence interval, - 10.7 to 17.7%; P = .6297). Patients treated with lansoprazole, esomeprazole, pantoprazole, and rabeprazole exhibited no significant differences in PRU or PI levels compared with those treated without PPIs. By contrast, patients treated with dexlansoprazole exhibited a significantly decreased level of PI (25.7% ± 24.3% vs 14.0% ± 21.6%, P = .0297) and responsiveness to clopidogrel under the criterion PI > 20% (adjusted absolute risk: 10.5%; 95% confidence interval: 2.6% to 43.6%; P = .0274). CONCLUSION No robust interaction between clopidogrel and PPIs was found, but caution should be exercised in the concomitant use of dexlansoprazole and clopidogrel in Asians.
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Affiliation(s)
- Sheng-Feng Lin
- School of Public Health, College of Public Health, Taipei Medical University, Taipei
- Department of Clinical Pathology, Far Eastern Memorial Hospital
- Department of Neurology, Far Eastern Memorial Hospital
- Division of Hospitalist, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei
| | - Pei-Chin Lin
- Department of Clinical Pathology, Far Eastern Memorial Hospital
| | - Chih-Chun Chang
- Department of Clinical Pathology, Far Eastern Memorial Hospital
- Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, Yilan
| | - Wei-Lun Chang
- Department of Pharmacy, Far Eastern Memorial Hospital, New Taipei
| | - Fang-Yeh Chu
- Department of Clinical Pathology, Far Eastern Memorial Hospital
- Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan City
- Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu City
- School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei City, Taiwan
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Ang SS, Rao SH, Rizkalla NA, Cha S, Yang Y, Chacko M, Gurakar AO, Ottmann SE, Pustavoitau A. Intraoperative Type I Acute Myocardial Infarction During Liver Transplant Requiring Intra-Aortic Balloon Pump: A Case Report. EXP CLIN TRANSPLANT 2020; 20:782-785. [PMID: 33272160 DOI: 10.6002/ect.2020.0205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intra-operative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.
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Affiliation(s)
- Sheryl S Ang
- From the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA
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Xiang Q, Wang Z, Zhang HX, Liu ZY, Xie QF, Hu K, Mu GY, Ma LY, Zhang Z, Jiang J, Cui YM. Predicting ischaemic events using platelet reactivity in patients receiving clopidogrel: Indirect meta-comparison among VerifyNow, light transmission aggregometry and thromboelastography. Basic Clin Pharmacol Toxicol 2020; 127:309-319. [PMID: 32374907 DOI: 10.1111/bcpt.13429] [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: 01/21/2020] [Revised: 04/30/2020] [Accepted: 04/30/2020] [Indexed: 11/29/2022]
Abstract
The present study compared performances of the three major methods used for assessing platelet reactivity (PR)-VerifyNow, light transmission aggregometry (LTA) and thromboelastography (TEG)-to predict ischaemic events in patients receiving clopidogrel. PubMed, EMBASE and the Cochrane Library were searched from their inception to April 2019 for prospective studies that examined PR using VerifyNow, LTA or TEG and the incidence of ischaemic events. The investigated diagnostic indices include sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio and area under the receiver operating characteristic curves (AUC) of VerifyNow, LTA and TEG, respectively. A total of 26 prospective studies involving 22 185 patients were included in the analysis. The pooled AUC was 0.71 (95% CI: 0.67-0.75) for VerifyNow, 0.60 (95% CI: 0.55-0.64) for LTA and 0.81 (95% CI: 0.77-0.84) for TEG. Results of indirect comparisons indicated the AUC of VerifyNow was higher than that of LTA (1.18, 95% CI: 1.08-1.30) and lower than that of TEG (0.88, 95% CI: 0.82-0.94). TEG outperformed the other two methods for assessing PR in all predictive measures, including sensitivity, specificity, PLR and NLR. Despite a lack of studies that directly compared the three methods, our findings suggest that TEG should be recommended.
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Affiliation(s)
- Qian Xiang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Zhe Wang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Han-Xu Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Zhi-Yan Liu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Qiu-Fen Xie
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Kun Hu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Guang-Yan Mu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Ling-Yue Ma
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Zhuo Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Jie Jiang
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Yi-Min Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China
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Liu Z, Tian R, Wang Y, Chen Q, Li J, Xu L, Zhang S. Platelet Inhibition with Ticagrelor versus Clopidogrel in Diabetic Patients after Percutaneous Coronary Intervention for Chronic Coronary Syndromes. Thromb Haemost 2020; 120:1221-1229. [PMID: 32668483 DOI: 10.1055/s-0040-1713375] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Clopidogrel is currently the only P2Y12 inhibitor with class I recommendation in patients after percutaneous coronary intervention (PCI) for chronic coronary syndromes (CCS). Diabetic patients have reduced therapeutic response to clopidogrel. PURPOSE This study assessed the antiplatelet effect of ticagrelor versus clopidogrel in diabetic patients after recent PCI for CCS. METHODS Eligible patients were randomly assigned to receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily, in addition to aspirin 100 mg once daily for 15 days. P2Y12 reaction unit (PRU) and percent inhibition were measured by VerifyNow P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as PRU > 208. Bleeding was assessed by the Platelet Inhibition and Patient Outcomes criteria. Cardiac ischemic events were evaluated as adverse events. RESULTS The baseline characteristics of the patients (n = 39) were well balanced between the two groups. Both before and 2 to 4 hours after the final study dose on day 15, PRU was lower (41.3 ± 35.8 vs. 192.6 ± 49.5, p < 0.001; 36.6 ± 25.8 vs. 187.6 ± 70.9, p < 0.001), percent inhibition was higher (83.0% [70.5%, 96.0%] vs. 16.0% [0%, 25.0%], p < 0.001; 85.0% [76.0%, 96.5%] vs. 25.0% [0%, 39.0%], p < 0.001), and HOPR occurred less frequently (0% [0/20] vs. 26.3% [5/19], p = 0.020; 0% [0/20] vs. 31.6% [6/19], p = 0.008) in the ticagrelor group (n = 20) compared with the clopidogrel group (n = 19). No major or minor bleeding, or serious adverse events occurred in both groups. CONCLUSION Ticagrelor achieved greater peak and trough platelet inhibition than did clopidogrel in diabetic patients after recent PCI for CCS, which suggests the potential use of ticagrelor in this clinical setting.
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Affiliation(s)
- Zhenyu Liu
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ran Tian
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Wang
- Medical Research and Biometrics Center, Fu-Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Chen
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyi Li
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lihong Xu
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuyang Zhang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Numasawa Y, Sawano M, Fukuoka R, Ejiri K, Kuno T, Shoji S, Kohsaka S. Antithrombotic Strategy for Patients with Acute Coronary Syndrome: A Perspective from East Asia. J Clin Med 2020; 9:jcm9061963. [PMID: 32585929 PMCID: PMC7356748 DOI: 10.3390/jcm9061963] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/14/2020] [Accepted: 06/18/2020] [Indexed: 12/21/2022] Open
Abstract
Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention has become the standard of care, particularly in patients with acute coronary syndrome (ACS). Current clinical guidelines recommend novel P2Y12 inhibitors (e.g., prasugrel or ticagrelor) in addition to aspirin based on the results of representative randomized controlled trials conducted predominantly in Western countries. These agents were superior to clopidogrel in reducing the composite ischemic events, with a trade-off of the increased bleeding events. However, multiple differences exist between East Asian and Western patients, especially with respect to their physique, thrombogenicity, hemorrhagic diathesis, and on-treatment platelet reactivity. Recent studies from East Asian countries (e.g., Japan or South Korea) have consistently demonstrated that use of novel P2Y12 inhibitors is associated with a higher risk of bleeding events than use of clopidogrel, despite borderline statistical difference in the incidence of composite ischemic events. Additionally, multiple studies have shown that the optimal duration of DAPT may be shorter in East Asian than Western patients. This review summarizes clinical studies of antithrombotic strategies in East Asian patients with ACS. Understanding these differences in antithrombotic strategies including DAPT and their impacts on clinical outcomes will aid in selection of the optimal tailored antithrombotic therapy for patients with ACS.
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Affiliation(s)
- Yohei Numasawa
- Department of Cardiology, Japanese Red Cross Ashikaga Hospital, Ashikaga 326-0843, Japan
- Correspondence: ; Tel.: +81-284-21-0121; Fax: +81-284-21-6810
| | - Mitsuaki Sawano
- Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (R.F.); (S.S.); (S.K.)
| | - Ryoma Fukuoka
- Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (R.F.); (S.S.); (S.K.)
| | - Kentaro Ejiri
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan;
| | - Toshiki Kuno
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003, USA;
| | - Satoshi Shoji
- Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (R.F.); (S.S.); (S.K.)
| | - Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (R.F.); (S.S.); (S.K.)
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Association of CYP2C19*2 polymorphisms and high on-treatment platelet reactivity in acute myocardial infarction or coronary artery in-stent restenosis patients during dual antiplatelet therapy. MEDICINE IN DRUG DISCOVERY 2020. [DOI: 10.1016/j.medidd.2020.100038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Kim MJ, Patel P, Vyas N, Leveque C, Diaz O, Salazar E. A 70-Year-Old Female with Unexpected Platelet Function Testing Results. Lab Med 2020; 51:310-314. [PMID: 31665395 DOI: 10.1093/labmed/lmz070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
A 70-year-old female with a history of hypertension and left A2 segment aneurysm was scheduled for pipeline embolization device (PED) placement. Preinterventional antiplatelet prophylaxis included aspirin and ticagrelor. Unexpectedly, after 13 days of treatment, VerifyNow showed a P2Y12 reaction unit (PRU) value of 216, approximately >5 times the mean PRU of other patients on aspirin and ticagrelor. We confirmed platelet reactivity and ticagrelor resistance with light transmission aggregometry. Antiplatelet therapy was switched to prasugrel, and aspirin was continued. Eight days later, the P2Y12 reaction value (PRU) was 164. PED was placed without complications. Unlike clopidogrel, ticagrelor is a direct P2Y12 inhibitor that does not require metabolism to an active metabolite. Ticagrelor resistance is very rarely reported. To the best of our knowledge, there has been no case of ticagrelor resistance reported in the context of pre-PED placement prophylaxis.
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Affiliation(s)
- Moon Joo Kim
- Houston Methodist Hospital, Department of Pathology and Genomic Medicine, Houston, Texas
| | - Pragna Patel
- Houston Methodist Hospital, Department of Neurointerventional Radiology, Houston, Texas
| | - Niti Vyas
- Houston Methodist Hospital, Department of Pathology and Genomic Medicine, Houston, Texas
| | - Christopher Leveque
- Houston Methodist Hospital, Department of Pathology and Genomic Medicine, Houston, Texas
| | - Orlando Diaz
- Houston Methodist Hospital, Department of Neurointerventional Radiology, Houston, Texas
| | - Eric Salazar
- Houston Methodist Hospital, Department of Pathology and Genomic Medicine, Houston, Texas
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Ahn JH, Ahn Y, Jeong MH, Kim JH, Hong YJ, Sim DS, Kim MC, Hwang JY, Yoon JH, Seong IW, Hur SH, Oh SK. Ticagrelor versus clopidogrel in acute myocardial infarction patients with multivessel disease; From Korea Acute Myocardial Infarction Registry-National Institute of Health. J Cardiol 2020; 75:478-484. [DOI: 10.1016/j.jjcc.2019.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 10/24/2019] [Accepted: 11/17/2019] [Indexed: 01/23/2023]
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Arnold SV, Bhatt DL, Barsness GW, Beatty AL, Deedwania PC, Inzucchi SE, Kosiborod M, Leiter LA, Lipska KJ, Newman JD, Welty FK. Clinical Management of Stable Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus: A Scientific Statement From the American Heart Association. Circulation 2020; 141:e779-e806. [PMID: 32279539 DOI: 10.1161/cir.0000000000000766] [Citation(s) in RCA: 169] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Although cardiologists have long treated patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (T2DM), T2DM has traditionally been considered just a comorbidity that affected the development and progression of the disease. Over the past decade, a number of factors have shifted that have forced the cardiology community to reconsider the role of T2DM in CAD. First, in addition to being associated with increased cardiovascular risk, T2DM has the potential to affect a number of treatment choices for CAD. In this document, we discuss the role that T2DM has in the selection of testing for CAD, in medical management (both secondary prevention strategies and treatment of stable angina), and in the selection of revascularization strategy. Second, although glycemic control has been recommended as a part of comprehensive risk factor management in patients with CAD, there is mounting evidence that the mechanism by which glucose is managed can have a substantial impact on cardiovascular outcomes. In this document, we discuss the role of glycemic management (both in intensity of control and choice of medications) in cardiovascular outcomes. It is becoming clear that the cardiologist needs both to consider T2DM in cardiovascular treatment decisions and potentially to help guide the selection of glucose-lowering medications. Our statement provides a comprehensive summary of effective, patient-centered management of CAD in patients with T2DM, with emphasis on the emerging evidence. Given the increasing prevalence of T2DM and the accumulating evidence of the need to consider T2DM in treatment decisions, this knowledge will become ever more important to optimize our patients' cardiovascular outcomes.
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Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients. Cardiovasc Drugs Ther 2020; 33:129-137. [PMID: 30783954 DOI: 10.1007/s10557-019-06855-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
PURPOSE The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION NCT02101437.
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De Gregorio MG, Marcucci R, Migliorini A, Gori AM, Giusti B, Vergara R, Paniccia R, Carrabba N, Marchionni N, Valenti R. Clinical Implications of "Tailored" Antiplatelet Therapy in Patients With Chronic Total Occlusion. J Am Heart Assoc 2020; 9:e014676. [PMID: 32067582 PMCID: PMC7070214 DOI: 10.1161/jaha.119.014676] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Background Clopidogrel nonresponsiveness is a prognostic marker after percutaneous coronary intervention. Prasugrel and ticagrelor provide a better platelet inhibition and represent the first‐line antiplatelet treatment in acute coronary syndrome. We sought to assess the prognostic impact of high platelet reactivity (HPR) and the potential clinical benefit of a “tailored” escalated or changed antiplatelet therapy in patients with chronic total occlusion. Methods and Results From Florence CTO‐PCI (chronic total occlusion‐percutaneous coronary intervention) registry, platelet function assessed by light transmission aggregometry, was available for 1101 patients. HPR was defined by adenosine diphosphate test ≥70% and optimal platelet reactivity by adenosine diphosphate test <70%. The endpoint of the study was long‐term cardiac survival. Patients were stratified according to light transmission aggregometry results: optimal platelet reactivity (82%) and HPR (18%). Means for the adenosine diphosphate test were 44±16% versus 77±6%, respectively. Three‐year survival was significantly higher in the optimal platelet reactivity group compared with HPR patients (95.3±0.8% versus 86.2±2.8%; P<0.001). With the availability of new P2Y12 inhibitors, a deeper platelet inhibition (46±17%) and similar survival to the optimal platelet reactivity group were achieved in patients with HPR on clopidogrel therapy after escalation. Conversely, HPR on clopidogrel therapy “not switched” was associated with cardiac mortality (hazard ratio 2.37; P=0.003) after multivariable adjustment. Conclusions HPR on treatment could be a modifiable prognostic marker by new antiaggregants providing a deeper platelet inhibition associated with clinical outcome improvement in complex chronic total occlusion patients. A “tailored” antiplatelet therapy, also driven by the entity of platelet inhibition, could be useful in these high risk setting patients.
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Affiliation(s)
- Maria Grazia De Gregorio
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy.,Experimental and Clinical Medicine Department University of Florence Italy
| | - Rossella Marcucci
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy.,Experimental and Clinical Medicine Department University of Florence Italy
| | - Angela Migliorini
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy
| | - Anna Maria Gori
- Experimental and Clinical Medicine Department University of Florence Italy
| | - Betti Giusti
- Experimental and Clinical Medicine Department University of Florence Italy
| | - Ruben Vergara
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy
| | - Rita Paniccia
- Experimental and Clinical Medicine Department University of Florence Italy
| | - Nazario Carrabba
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy
| | - Niccolò Marchionni
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy.,Experimental and Clinical Medicine Department University of Florence Italy
| | - Renato Valenti
- Cardiovascular Department Azienda Ospedaliero-Universitaria Careggi Florence Italy
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Schreuder MM, Badal R, Boersma E, Kavousi M, Roos-Hesselink J, Versmissen J, Visser LE, Roeters van Lennep JE. Efficacy and Safety of High Potent P2Y 12 Inhibitors Prasugrel and Ticagrelor in Patients With Coronary Heart Disease Treated With Dual Antiplatelet Therapy: A Sex-Specific Systematic Review and Meta-Analysis. J Am Heart Assoc 2020; 9:e014457. [PMID: 32063118 PMCID: PMC7070195 DOI: 10.1161/jaha.119.014457] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex‐specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y12 inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y12 inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow‐up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80–1.00; men: RR, 0.84 [95% CI, 0.79–0.91) (P for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high‐potency dual antiplatelet therapy (RR, 1.18 [95% CI, 0.98–1.41] versus RR, 1.03 [95% CI, 0.93–1.14]) (P for interaction=0.20). Conclusions The small and statistically insignificant difference in efficacy and safety estimates of high‐potency dual antiplatelet therapy between women and men following percutaneous coronary intervention/acute coronary syndrome do not justify differential dual antiplatelet therapy treatment for both sexes.
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Affiliation(s)
- Michelle M Schreuder
- Department of Internal Medicine Erasmus Medical Centre Rotterdam The Netherlands
| | - Ricardo Badal
- Department of Internal Medicine Erasmus Medical Centre Rotterdam The Netherlands
| | - Eric Boersma
- Department of Epidemiology Erasmus Medical Centre Rotterdam The Netherlands
| | - Maryam Kavousi
- Department of Epidemiology Erasmus Medical Centre Rotterdam The Netherlands
| | | | - Jorie Versmissen
- Department of Internal Medicine Erasmus Medical Centre Rotterdam The Netherlands
| | - Loes E Visser
- Department of Epidemiology Erasmus Medical Centre Rotterdam The Netherlands
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Walcott BP, Lawton MT. Carotid artery occlusion and revascularization in the management of meningioma. HANDBOOK OF CLINICAL NEUROLOGY 2020; 170:209-216. [PMID: 32586492 DOI: 10.1016/b978-0-12-822198-3.00041-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
As the carotid artery courses through the skull base and into the subarachnoid space, it lies in close proximity to regions notorious for meningioma growth. Although infrequent, the growth of these tumors can compromise blood flow through the artery, putting the downstream territory at risk for stroke. In other scenarios, removal of these tumors sometimes requires planning to accomplish both tumor removal and revascularization in the same procedure when then the tumor invades the artery. Since revascularization (bypass surgery) is best performed on a nonemergent basis, it should be given consideration in the preoperative setting. Crisis situations related to intraoperative iatrogenic injury are managed methodically by determining the site of vessel injury and then deciding whether a primary repair or bypass procedure is necessary. The mainstays of revascularization procedures of the carotid artery include flow augmentation and flow replacement, with the superficial temporal artery and external carotid artery being the donor sites, respectively. Although tumor control or cure can be accomplished with surgical, radiosurgical, or combined methods, attention to vascular structures and ensuring blood flow preservation as part of the treatment plan is an important tenet in meningioma surgery.
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Affiliation(s)
- Brian P Walcott
- Department of Neurological Surgery, University of Southern California, Los Angeles, CA, United States
| | - Michael T Lawton
- Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, United States.
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Marsousi N, Daali Y, Fontana P, Reny JL, Ancrenaz-Sirot V, Calmy A, Rudaz S, Desmeules JA, Samer CF. Impact of Boosted Antiretroviral Therapy on the Pharmacokinetics and Efficacy of Clopidogrel and Prasugrel Active Metabolites. Clin Pharmacokinet 2019; 57:1347-1354. [PMID: 29453687 DOI: 10.1007/s40262-018-0637-6] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Prasugrel and clopidogrel are inhibitors of the ADP-P2Y12 platelet receptor used in acute coronary syndrome patients. They require bioactivation via isoenzymes such as cytochrome P450 (CYP) 3A4, CYP2C19 and CYP2B6. Ritonavir and cobicistat are potent CYP3A inhibitors, prescribed as pharmacokinetic (PK) enhancers in the treatment of human immunodeficiency virus (HIV) infection. METHODS In this study, the impact of boosted antiretroviral therapies (ARTs) on the PK of clopidogrel and prasugrel active metabolites (AMs), and on the efficacy of prasugrel and clopidogrel, were evaluated in a randomized crossover clinical trial. RESULTS A significantly lower exposure to clopidogrel AM [3.2-fold lower area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax)] and prasugrel AM (2.1-fold and 1.7-fold lower AUC and Cmax) were demonstrated in HIV-infected patients treated with boosted ARTs compared with healthy controls; however, a differential impact was observed on platelet inhibition between clopidogrel and prasugrel. Clopidogrel 300 mg induced adequate (although modest) platelet inhibition in all healthy subjects, while platelet inhibition was insufficient in 44% of HIV patients. On the contrary, prasugrel 60 mg induced a potent platelet inhibition in both healthy and HIV-infected subjects. CONCLUSION Prasugrel appears to remain an adequate antiplatelet agent in HIV-infected patients and could be preferred to clopidogrel in this context, regardless of the metabolic interaction and inhibition of its bioactivation pathways.
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Affiliation(s)
- Niloufar Marsousi
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland
- School of Pharmaceutical Sciences, Geneva and Lausanne Universities, Geneva, Switzerland
| | - Youssef Daali
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland
- School of Pharmaceutical Sciences, Geneva and Lausanne Universities, Geneva, Switzerland
- Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland
| | - Pierre Fontana
- Faculty of Medicine, Geneva University, Geneva, Switzerland
- Division of Angiology and Haemostasis, Geneva University Hospitals, Geneva, Switzerland
- Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Jean-Luc Reny
- Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Department of General Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland
| | - Virginie Ancrenaz-Sirot
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland
| | - Alexandra Calmy
- Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
| | - Serge Rudaz
- School of Pharmaceutical Sciences, Geneva and Lausanne Universities, Geneva, Switzerland
- Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland
| | - Jules Alexandre Desmeules
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland
- School of Pharmaceutical Sciences, Geneva and Lausanne Universities, Geneva, Switzerland
- Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland
- Faculty of Medicine, Geneva University, Geneva, Switzerland
| | - Caroline Flora Samer
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland.
- Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland.
- Faculty of Medicine, Geneva University, Geneva, Switzerland.
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Lattuca B, Silvain J, Yan Y, Pouillot C, Cuisset T, Cayla G, Henry P, Diallo A, Elhadad S, Rangé G, Lhermusier T, Boueri Z, Motreff P, Carrié D, Vicaut E, Montalescot G, Collet JP. Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy: Pharmacodynamic Insights From the ARCTIC Study. Circ Cardiovasc Interv 2019; 12:e007749. [PMID: 31694410 DOI: 10.1161/circinterventions.118.007749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment. METHODS We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y12 test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status. RESULTS Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74-1.18]; P=0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22-7.59]; P=0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40-1.58]; P=0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96-8.41]; P=0.06) in HPR versus non-HPR patients. CONCLUSIONS The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00827411.
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Affiliation(s)
- Benoit Lattuca
- Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.).,Cardiology Department, Caremeau University Hospital, ACTION Study Group, Montpellier University, Nîmes, France (B.L., G.C.)
| | - Johanne Silvain
- Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.)
| | - Yan Yan
- Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.).,Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, China (Y.Y.)
| | - Christophe Pouillot
- Cardiology Department, Sainte Clotilde Clinic, St. Denis de la Réunion, France (C.P.)
| | - Thomas Cuisset
- ACTION Study Group, Cardiology Department, La Timone Hospital, Marseille, France (T.C.)
| | - Guillaume Cayla
- Cardiology Department, Caremeau University Hospital, ACTION Study Group, Montpellier University, Nîmes, France (B.L., G.C.)
| | - Patrick Henry
- Cardiology Department (P.H.), Lariboisière University Hospital, Paris, France
| | - Abdourahmane Diallo
- ACTION Study Group, Epidemiology and Clinic Research Unit (A.D., E.V.), Lariboisière University Hospital, Paris, France
| | - Simon Elhadad
- Cardiology department, Lagny-Marne la Vallée Hospital, France (S.E.)
| | - Grégoire Rangé
- Cardiology department, Chartres Hospital, Le Coudray, France (G.R.)
| | - Thibault Lhermusier
- Cardiology Department, Rangueil University Hospital, Toulouse, France (T.L., D.C.)
| | - Ziad Boueri
- Cardiology Department, Bastia Hospital, France (Z.B.)
| | - Pascal Motreff
- Cardiology Department, Gabriel Montpied University Hospital, Clermont-Ferrand, France (P.M.)
| | - Didier Carrié
- Cardiology Department, Rangueil University Hospital, Toulouse, France (T.L., D.C.)
| | - Eric Vicaut
- ACTION Study Group, Epidemiology and Clinic Research Unit (A.D., E.V.), Lariboisière University Hospital, Paris, France
| | - Gilles Montalescot
- Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.)
| | - Jean-Philippe Collet
- Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.)
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Sibbing D, Aradi D, Alexopoulos D, ten Berg J, Bhatt DL, Bonello L, Collet JP, Cuisset T, Franchi F, Gross L, Gurbel P, Jeong YH, Mehran R, Moliterno DJ, Neumann FJ, Pereira NL, Price MJ, Sabatine MS, So DY, Stone GW, Storey RF, Tantry U, Trenk D, Valgimigli M, Waksman R, Angiolillo DJ. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention. JACC Cardiovasc Interv 2019; 12:1521-1537. [DOI: 10.1016/j.jcin.2019.03.034] [Citation(s) in RCA: 250] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 03/10/2019] [Accepted: 03/11/2019] [Indexed: 12/22/2022]
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Shlofmitz E, Shlofmitz R, Lee MS. The Role of Novel Oral Anticoagulants and Antiplatelet Therapy after Percutaneous Coronary Intervention: Individualizing Therapy to Optimize Outcomes. Korean Circ J 2019; 49:645-656. [PMID: 31347321 PMCID: PMC6675700 DOI: 10.4070/kcj.2019.0185] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 06/24/2019] [Indexed: 11/23/2022] Open
Abstract
The number of patients undergoing percutaneous coronary intervention (PCI) who mandate additional oral anticoagulant therapy has been increasing. Dual antiplatelet therapy (DAPT) is associated with reduced ischemic events including stent thrombosis, myocardial infarction and stroke following PCI. However, the tradeoff is an increased risk for bleeding while on DAPT. The addition of a novel oral anticoagulant (NOAC) further increases the likelihood of bleeding while on antiplatelet therapy. Thus, the overall risks and benefits for each patient undergoing PCI on NOAC must be assessed and therapy individualized to ensure optimal therapy for each unique situation. Patients on NOAC undergoing PCI should undergo routine assessment with intravascular imaging as the role of high-risk lesion-related features have increased importance prior to determining optimal duration of treatment with DAPT. We review the best practices for the pharmacologic management of patients requiring anticoagulation with NOAC who are treated with PCI and require antiplatelet therapy.
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Affiliation(s)
- Evan Shlofmitz
- MedStar Washington Hospital Center, Washington, D.C., USA
| | | | - Michael S Lee
- Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
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42
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The prognostic value of multiple electrode aggregometry and light transmittance aggregometry in stable cardiovascular patients with type 2 diabetes mellitus. Thromb Res 2019; 180:47-54. [PMID: 31202191 DOI: 10.1016/j.thromres.2019.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/15/2019] [Accepted: 06/03/2019] [Indexed: 01/10/2023]
Abstract
AIM Limited data are available regarding the clinical relevance of platelet function measurements in stable patients with coronary artery disease (CAD). Our aim is to evaluate the agreement between multiple electrode aggregometry (MEA) and light transmittance aggregometry (LTA) in detecting clopidogrel low responders and their prognostic value in CAD patients with type 2 diabetes mellitus (T2DM) on dual platelet inhibition. METHODS LTA and MEA were performed in 122 stable cardiovascular patients with T2DM. The upper quartile of patients according to maximum LTA (LTAmax) and MEA measurements were defined as clopidogrel low responders. Agreement between the two methods was evaluated by kappa statistics. We assessed the potential correlation between antiplatelet response and clinical outcome and the optimal cutoff value according to ROC analysis to predict the occurrence of major adverse cardiovascular events (MACE), during 1-year follow-up period. RESULTS Cohen's kappa coefficients (0.214) indicated fair agreement (70.2%) between LTA and MEA. A total of 25 MACE occurred in 108 patients (23.1%). Patients with MACE had higher LTAmax than those without (57.1 ± 16.5 vs 49.3 ± 18.3, respectively, p = 0.023). MEA measurements were similar between patients with and without MACE (30.1 ± 15.4 vs 30.6 ± 20.8, respectively; p = 0.84). Multiple logistic regression showed LTAmax response as an independent predictor of death from cardiovascular causes (Odds Ratio, adjusted:0.2;0.05-0.81). ROC analysis indicated that LTAmax cutoff of 62.5% best predicted death (AUC = 0.67, sensitivity = 78%, specificity = 61.5%). CONCLUSIONS The assessment of platelet responsiveness remains highly test-specific. Our results support the prognostic role of LTA, but not MEA testing, for death risk evaluation in stable cardiovascular T2DM patients.
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Kim MS, Song HJ, Lee J, Yang BR, Choi NK, Park BJ. Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study. Clin Pharmacol Ther 2019; 106:182-194. [PMID: 30648733 DOI: 10.1002/cpt.1361] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 12/16/2018] [Indexed: 12/16/2022]
Abstract
Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007-2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4-metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45), unlike CYP3A4-metabolized statins (HR 1.03, 95% CI 0.98-1.07). PPIs with high CYP2C19-inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02-1.61). Joint effects of PPIs and CYP3A4-metabolized statins were nonsignificant (relative excess risk due to interaction -0.14, 95% CI -0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4-metabolized statins did not exacerbate PPI-associated risks.
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Affiliation(s)
- Mi-Sook Kim
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.,Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Hong Ji Song
- Department of Family Medicine, Health Promotion Center, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Joongyub Lee
- Department of Prevention and Management, Inha University Hospital, Incheon, Korea
| | - Bo Ram Yang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Nam-Kyong Choi
- Department of Health Convergence, College of Science & Industry Convergence, Ewha Womans University, Seoul, Korea
| | - Byung-Joo Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
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44
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Wang Z, Xie Q, Xiang Q, Gong Y, Jiang J, Cui Y. Predictive Value of Methods Measuring Platelet Activation for Ischemic Events in Patients Receiving Clopidogrel: A Systematic Review and Meta-analysis. Curr Pharm Des 2019; 24:5313-5333. [PMID: 30727868 DOI: 10.2174/1381612825666190206114724] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 01/26/2019] [Indexed: 11/22/2022]
Abstract
This study investigates the efficiency and predictive value of light-transmission aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) and VerifyNow for ischemia in patients undergoing percutaneous coronary intervention (PCI). Studies that used LTA, VASP or VerifyNow to predict ischemia were included, and their quality and efficiency were analyzed using Review Manager 5.3. The sensitivity and specificity of subgroup studies based on the outcome, cut-off value, and follow-up days were calculated and the summary ROC (sROC) curves were compared after having been fitted. Thirty-one studies including a total of 17,314 participants were analyzed. LTA, VASP and VerifyNow presented a considerable efficiency in predicting ischemic clinical events. In the subgroup analysis, the sensitivities of LTA, VASP and VerifyNow in predicting cardiac death, all-cause death, myocardial infarction, stent thrombosis, stroke, and revascularization were 0.40/0.63/0.62, 0.47/0.56/0.39, 0.40/0.48/0.60, 0.44/0.58/0.70, 0.29/not applicable/0.60 and 0.44/0.57/0.37, respectively and the specificities of LTA, VASP, and VerifyNow were 0.85/0.48/0.63, 0.73/0.52/0.63, 0.74/0.55/0.64, 0.75/0.47/0.61, 0.72/not applicable/ 0.61, and 0.70/0.47/0.67, respectively. LTA showed a higher sensitivity in predicting the outcomes over six months than those within six months, while VerifyNow prediction sensitivity was found to be higher within six months. Meanwhile, VerifyNow showed no statistically significant higher AUC of sROC in comparison to LTA and VASP in predicting ischemic events in patients undergoing clopidogrel treatment. The cut-off values of LTA, VASP and VerifyNow were suggested to be 56%, 50% and 235 respectively according to our study.
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Affiliation(s)
- Zhe Wang
- Department of Pharmacy, Peking University First Hospital, Beijing, China.,Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Peking University Health Science Center, Beijing, China
| | - Qiufen Xie
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Qian Xiang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Yanjun Gong
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Jie Jiang
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China
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Lee SN, Moon D, Sung MK, Moon KW, Yoo KD. Impact of platelet reactivity on long-term prognosis in Korean patients receiving percutaneous coronary intervention. Platelets 2019; 30:1030-1035. [PMID: 30601072 DOI: 10.1080/09537104.2018.1562172] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Both high and low platelet responses to clopidogrel are highly associated with mortality. A therapeutic window for platelet reactivity was recently determined to be an important factor for improving clinical outcomes after percutaneous coronary intervention (PCI). We evaluated the impact of the antiplatelet activity of clopidogrel on long-term clinical outcomes in Korean patients receiving PCI. We analyzed the clinical outcomes of 814 Korean patients undergoing PCI for a median of 48 months. Platelet reactivity on clopidogrel was measured with the VerifyNow P2Y12 assay. The primary endpoint was all-cause death at 4 years. Patients were classified into three groups according to the P2Y12 reaction unit (PRU): low platelet reactivity (LPR; PRU < 85), normal platelet reactivity (NPR; 85 ≤ PRU < 208), and high platelet reactivity (HPR; PRU ≥ 208). The incidence of all-cause death was 7.0% in the LPR group, 1.5% in the NPR group, and 6.2% in the HPR group (log-rank p = 0.002). Based on multivariate analyses, all-cause death was significantly higher in both the LPR and HPR groups than in the NPR group (LPR, hazard ratio [HR]: 5.095; 95% confidence interval [95% CI]: 1.360-19.080, p = 0.016; HPR, HR: 3.315; 95% CI: 1.145-9.593, p = 0.027). Both LPR and HPR were significantly associated with long-term mortality in Korean patients receiving PCI, which suggests that the therapeutic concept of PRU may be an important prognostic factor.
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Affiliation(s)
- Su Nam Lee
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea , Suwon , South Korea
| | - Donggyu Moon
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea , Suwon , South Korea
| | - Min Kyung Sung
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea , Suwon , South Korea
| | - Keon-Woong Moon
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea , Suwon , South Korea
| | - Ki-Dong Yoo
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea , Suwon , South Korea
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Ohno Y, Kitahara H, Fujii K, Kohno Y, Ariyoshi N, Nishi T, Fujimoto Y, Kobayashi Y. High residual platelet reactivity after switching from clopidogrel to low-dose prasugrel in Japanese patients with end-stage renal disease on hemodialysis. J Cardiol 2019; 73:51-57. [DOI: 10.1016/j.jjcc.2018.07.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 05/21/2018] [Accepted: 07/02/2018] [Indexed: 12/21/2022]
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47
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Laboratory Monitoring of Antiplatelet Therapy. Platelets 2019. [DOI: 10.1016/b978-0-12-813456-6.00036-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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48
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Frelinger AL. Platelet Function Testing in Clinical Research Trials. Platelets 2019. [DOI: 10.1016/b978-0-12-813456-6.00037-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Mansurova JA, Karazhanova LK. Independent Predictors of Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention During Hospitalization. KARDIOLOGIYA 2018; 58:22-29. [PMID: 30625093 DOI: 10.18087/cardio.2018.12.10205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 12/25/2018] [Indexed: 11/18/2022]
Abstract
PURPOSE to elucidate independent clinical and laboratory predictors of adverse cardiovascular events (ACVE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) with stenting in early inhospital period. MATERIALS AND METHODS We included in this prospective single center study 130 patients with ACS who underwent PCI with stenting. All patients prior to and after PCI received dual antiplatelet therapy with acetylsalicylic acid and clopidogrel. In 12-48 hours after PCI we measured residual platelet reactivity (RPR) using light aggregometry. In 57 patients simultaneously we performed genotyping of CYP2C19*2 polymorphisms. The following ACVE were used as end-points and were registered during inhospital observation (mean duration 9.7±3.2 days): sudden death, stent thrombosis, arterial thrombosis of other localization, recurrent angina, cardiac rhythm disturbances requiring special therapy. RESULTS Repetitive ACVE were observed in 32 patients. According to unifactorial regression analysis risk factors of their development were, ADP F-induced RPR (р<0.001), levels of creatinine (р<0.001), hemoglobin (р<0.001), and glucose (р=0.026), age (р=0.01), iron-deficiency anemia (р=0.01), left ventricular ejection fraction (р=0.004), number of stents (р=0.015). According to results of multifactorial regression analysis independent predictors of ACVE were: ADP-induced RPR >76 % (р=0.003), levels of creatinine >189 µmol / L (р=0.003), and hemoglobin <114 g / L (р=0.004). Significant effect of homozygous carriage of CYP2C19*2 (G681A) (А / А) on development of stent thrombosis was also detected (р=0.028). CONCLUSION ADP-induced RPR, levels of creatinine and hemoglobin were found to be independent predictors of inhospital ACVE after myocardial revascularization with stenting in patients with ACS.
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50
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Somuncu MU, Demir AR, Karakurt ST, Karakurt H, Karabag T. Long Term Cardiovascular Outcome Based on Aspirin and Clopidogrel Responsiveness Status in Young ST-Elevated Myocardial Infarction Patients. Arq Bras Cardiol 2018; 112:138-146. [PMID: 30570067 PMCID: PMC6371821 DOI: 10.5935/abc.20180251] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 07/23/2018] [Indexed: 11/20/2022] Open
Abstract
Background A subset of patients who take antiplatelet therapy continues to have
recurrent cardiovascular events which may be due to antiplatelet resistance.
The effect of low response to aspirin or clopidogrel on prognosis was
examined in different patient populations. Objective We aimed to investigate the prevalence of poor response to dual antiplatelet
therapy and its relationship with major adverse cardiovascular events (MACE)
in young patients with ST-elevation myocardial infarction (STEMI). Methods In our study, we included 123 patients under the age of 45 with STEMI who
underwent primary percutaneous intervention. A screening procedure to
determine both aspirin and clopidogrel responsiveness was performed on the
fifth day of admission. We followed a 2x2 factorial design and patients were
allocated to one of four groups, according to the presence of aspirin and/or
clopidogrel resistance. Patients were followed for a three-year period. A
p-value less than 0.05 was considered statistically significant. Results We identified 48% of resistance against one or more antiplatelet in young
patients with STEMI. More MACE was observed in patients with poor response
to dual platelet therapy or to clopidogrel compared those with adequate
response to the dual therapy (OR: 1.875, 1.144-3.073, p < 0.001; OR:
1.198, 0.957-1.499, p = 0.036, respectively). After adjustment for potential
confounders, we found that poor responders to dual therapy had 3.3 times
increased odds for three-year MACE than those with adequate response to the
dual therapy. Conclusion Attention should be paid to dual antiplatelet therapy in terms of increased
risk for cardiovascular adverse events especially in young patients with
STEMI.
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Affiliation(s)
- Mustafa Umut Somuncu
- Bulent Ecevit University - Faculty of Medicine -, Department of Cardiology, Zonguldak - Turkey
| | - Ali Riza Demir
- Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul - Turkey
| | - Seda Tukenmez Karakurt
- Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul - Turkey
| | - Huseyin Karakurt
- Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul - Turkey
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