|
1
|
Blaško P, Samoš M, Bolek T, Stančiaková L, Škorňová I, Péč MJ, Jurica J, Staško J, Mokáň M. Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth? J Clin Med 2022; 11:jcm11237211. [PMID: 36498785 PMCID: PMC9737839 DOI: 10.3390/jcm11237211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/12/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called "high on-treatment platelet reactivity" or "resistance") could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of "resistance" on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.
Collapse
Affiliation(s)
- Peter Blaško
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
- Out-Patient Clinic of Cardiology, 957 01 Banovce nad Bebravou, Slovakia
| | - Matej Samoš
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
- Correspondence: ; Tel.: +421-907-612-943 or +421-434-203-820
| | - Tomáš Bolek
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Lucia Stančiaková
- Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Ingrid Škorňová
- Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Martin Jozef Péč
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Jakub Jurica
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Ján Staško
- Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Marián Mokáň
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| |
Collapse
|
|
2
|
Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention. JACC Cardiovasc Interv 2022; 15:2270-2280. [DOI: 10.1016/j.jcin.2022.09.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 09/06/2022] [Accepted: 09/13/2022] [Indexed: 11/22/2022]
|
|
3
|
Khalid U, Bandeali S, Jones PG, Virani SS, Hira R, Hamzeh I, Chan PS, Kleiman NS, Lakkis N, Alam M. Prescription Patterns of Clopidogrel, Prasugrel, and Ticagrelor After Percutaneous Coronary Intervention With Stent Implantation (from the NCDR PINNACLE Registry). Am J Cardiol 2019; 124:1807-1812. [PMID: 31668345 DOI: 10.1016/j.amjcard.2019.09.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 09/09/2019] [Accepted: 09/09/2019] [Indexed: 11/20/2022]
Abstract
The use of prasugrel and ticagrelor as part of dual antiplatelet therapy is increasing in patients after percutaneous coronary intervention (PCI). Accordingly, we aimed to evaluate their prescription patterns in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry. We analyzed patients enrolled in NCDR PINNACLE registry from January 2013 to March 2015 who underwent PCI with drug-eluting stent and were prescribed dual antiplatelet therapy. All patients received aspirin. The primary study outcome was a 3-level variable denoting the second antiplatelet agent prescribed: (1) clopidogrel, (2) prasugrel, or (3) ticagrelor. Baseline characteristics were compared among the 3 groups. Odds ratios and 95% credible intervals were calculated from a nested hierarchical Bayesian logistic regression models to identify independent predictors of prescription of antiplatelet medications, incorporating practice and provider as random effects. Our study cohort consisted of 26,710 patients during our study period January 2013 to March 2015. Seventy nine percent of patients were prescribed clopidogrel, 12% prasugrel, and 11% ticagrelor. Patients aged ≥75 years, women, history of tobacco use, Peripheral Arterial Disease (PAD), hypertension, diabetes, previous vascular complication, heart failure, and stroke/transient ischemic attack were more likely to be on clopidogrel than prasugrel or ticagrelor. The relative percentages of ticagrelor and prasugrel were higher in patients with history of myocardial infarction, compared with those without myocardial infarction. In summary, our study highlights the prescription patterns associated with prescription of antiplatelet agents after PCI. We found that both ticagrelor and prasugrel were mostly prescribed per the current practice guidelines, thus reflecting appropriate guideline adherence by practices in NCDR PINNACLE registry.
Collapse
Affiliation(s)
- Umair Khalid
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
| | - Salman Bandeali
- Section of Cardiology, Texas Heart Institute, Houston, Texas
| | - Philip G Jones
- Saint Luke's Mid America Heart Institute, Kansas City, Missouri
| | - Salim S Virani
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Section of Cardiology, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Ravi Hira
- Section of Cardiology, Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington
| | - Ihab Hamzeh
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Paul S Chan
- Saint Luke's Mid America Heart Institute, Kansas City, Missouri
| | - Neal S Kleiman
- Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas
| | - Nasser Lakkis
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Mahboob Alam
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| |
Collapse
|
|
4
|
Ismail N, Jordan KP, Rao S, Kinnaird T, Potts J, Kadam UT, Mamas MA. Incidence and prognostic impact of post discharge bleeding post acute coronary syndrome within an outpatient setting: a systematic review. BMJ Open 2019; 9:e023337. [PMID: 30787079 PMCID: PMC6398751 DOI: 10.1136/bmjopen-2018-023337] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 11/19/2018] [Accepted: 01/23/2019] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE The primary objective was to determine the incidence of bleeding events post acute coronary syndrome (ACS) following hospital discharge. The secondary objective was to determine the prognostic impact of bleeding on mortality, major adverse cardiovascular events (MACE), myocardial re-infarction and rehospitalisation in the postdischarge setting. DESIGN A narrative systematic review. DATA SOURCE Medline, Embase, Amed and Central (Cochrane) were searched up to August 2018. STUDY SELECTION For the primary objective, randomised controlled trials (RCT) and observational studies reporting on the incidence of bleeding post hospital discharge were included. For the secondary objective, RCTs and observational studies that compared patients with bleeding versus those without bleeding post hospital discharge vis-à-vis mortality, MACE, myocardial re-infarction and rehospitalisation were included. RESULTS 53 studies (36 observational studies and 17 RCTs) with a combined cohort of 714 458 participants for the primary objectives and 187 317 for the secondary objectives were included. Follow-up ranged from 1 month to just over 4 years. The incidence of bleeding within 12 months post hospital discharge ranged from 0.20% to 37.5% in observational studies and between 0.96% and 39.4% in RCTs. The majority of bleeds occurred in the initial 3 months after hospital discharge with bruising the most commonly reported event. Major bleeding increased the risk of mortality by nearly threefold in two studies. One study showed an increased risk of MACE (HR 3.00,95% CI 2.75 to 3.27; p<0.0001) with bleeding and another study showed a non-significant association with rehospitalisation (HR 1.20,95% CI 0.95 to 1.52; p=0.13). CONCLUSION Bleeding complications following ACS management are common and continue to occur in the long term after hospital discharge. These bleeding complications may increase the risk of mortality and MACE, but greater evidence is needed to assess their long-term effects. PROSPERO REGISTRATION NUMBER CRD42017062378.
Collapse
Affiliation(s)
- Nafiu Ismail
- Research Institute for Primary Care and Health Sciences, Keele University, Newcastle, UK
| | - Kelvin P Jordan
- Research Institute for Primary Care and Health Sciences, Keele University, Newcastle, UK
| | - Sunil Rao
- The Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Tim Kinnaird
- Department of Cardiology, University Hospital of Wales, Cardiff, UK
| | - Jessica Potts
- Research Institute for Primary Care and Health Sciences, Keele University, Newcastle, UK
| | - Umesh T Kadam
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Mamas A Mamas
- Research Institute for Primary Care and Health Sciences, Keele University, Newcastle, UK
| |
Collapse
|
|
5
|
On-treatment platelet reactivity in the era of new ADP receptor blockers: data from a real-world clinical practice. ACTA MEDICA MARTINIANA 2018. [DOI: 10.2478/acm-2018-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Objectives: Several studies have questioned the need for platelet function testing in patients treated with new ADP receptor blockers (ADPRB). The aim of this study was to evaluate the prevalence of high on-treatment platelet reactivity (HTPR) among acute ST-elevation myocardial infarction (STEMI) patients treated with newer ADPRB.
Methods: A prospective study enrolling 44 acute previously ADPRB naive STEMI patients (31 men, 13 women) undergoing primary percutaneous coronary intervention (pPCI) was performed. Among the studied population 23 patients received prasugrel and 21 patients received ticagrelor. Antiplatelet response was tested with light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Samples were taken prior to coronary angiography (sample 1) and on the day after this procedure (sample 2).
Results: The mean platelet aggregation after induction with ADP was 51.7 ± 24.8% in sample 1 and 25.3 ± 20.1% in sample 2. An examination of VASP-P showed a mean platelet reactivity index of 56.8 ± 25.7% in sample 1 and 23.8 ± 23.1% in sample 2, respectively. The study identified 11.4% of patients in sample 2 as ADP receptor blocker non-responders. No significant differences were found between prasugrel-treated to ticagrelor-treated patients.
Conclusions: This pilot study demonstrated HTPR among acute STEMI patients treated with newer ADPRB.
Collapse
|
|
6
|
Strisciuglio T, Franco D, Di Gioia G, De Biase C, Morisco C, Trimarco B, Barbato E. Impact of genetic polymorphisms on platelet function and response to anti platelet drugs. Cardiovasc Diagn Ther 2018; 8:610-620. [PMID: 30498685 DOI: 10.21037/cdt.2018.05.06] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cardiovascular genomic consists in the identification of polymorphic genes responsible for the susceptibility to cardiovascular disease including coronary artery disease (CAD). Genes involved in platelet activation and aggregation play a key role in the predisposition to CAD. A considerable inter-variability of platelet response to agonists and to drugs exists and in particular the hyper-reactivity phenotype seems to be heritable. Besides glycoproteins and receptors expressed on platelets surface whose mutations significantly impact on platelet function, moreover researchers in the last decades have paid great attention to the genes involved in the response to anti-platelet drugs, considering their pivotal role in the treatment and outcomes of CAD patients especially those undergoing PCI. With the outbreak of advanced techniques developed to analyse human genetic footprints, researchers nowadays have shifted from genetic linkage analysis and a candidate gene approach toward genome-wide association (GWAS) studies and the analysis of miRNA-mRNA expression profiles.
Collapse
Affiliation(s)
- Teresa Strisciuglio
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Danilo Franco
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Giuseppe Di Gioia
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Chiara De Biase
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Carmine Morisco
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Bruno Trimarco
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Barbato
- Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
7
|
Saucedo JF, Cardillo TE, Jakubowski JA, Henneges C, Effron MB, Lipkin FR, Walker JR, Duvvuru S, Sundseth SS, Fisher HN, Angiolillo DJ, Diodati JG. Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients. Thromb Haemost 2017; 112:311-22. [DOI: 10.1160/th13-09-0747] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 02/27/2014] [Indexed: 11/05/2022]
Abstract
SummaryHigh on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, doubleblind, TRIPLET trial included a pre-defined comparison of HPR in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) following a placebo/600-mg clopidogrel loading dose (LD) immediately before a subsequent prasugrel 60-mg or 30-mg LD. Platelet reactivity was assessed using the VerifyNow® P2Y12 assay (P2Y12 Reaction Units, PRU) within 24 hours (h) following the placebo/clopidogrel LD (immediately prior to prasugrel LD), and at 2, 6, 24, 72 h following prasugrel LDs. The impact of CYP2C19 predicted metaboliser phenotype (extensive metaboliser [EM] and reduced metabolisers [RM]) on HPR status was also assessed. HPR (PRU ≥240) following the clopidogrel LD (prior to the prasugrel LD) was 58.5% in the combined clopidogrel LD groups. No significant difference was noted when stratified by time between the clopidogrel and prasugrel LDs (≤6 hs vs >6 h). At 6 h following the 2nd loading dose in the combined prasugrel LD groups, HPR was 7.1%, with 0% HPR by 72 h. There was no significant effect of CYP2C19 genotype on pharmacodynamic (PD) response following either prasugrel LD treatments at any time point, regardless of whether it was preceded by a clopidogrel 600-mg LD. In conclusion, in this study, patients with ACS intended for PCI showed a high prevalence of HPR after clopidogrel 600-mg LD regardless of metaboliser status. When prasugrel LD was added, HPR decreased substantially by 6 h, and was not seen by 72 h.
Collapse
|
|
8
|
Stavrou K, Koniari I, Gkizas V, Perperis A, Kontoprias K, Vogiatzi C, Bampouri T, Xanthopoulou I, Alexopoulos D. Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events. Thromb Haemost 2017; 112:551-7. [DOI: 10.1160/th14-02-0119] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 03/25/2014] [Indexed: 11/05/2022]
Abstract
SummaryPlatelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58–0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3–37.3 vs 84.6, 95% CI 73.6–95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01774955.
Collapse
|
|
9
|
Hernández Vera R, Padró T, Vilahur G, Badimon L. Antithrombotic therapy in obesity. Thromb Haemost 2017; 110:681-8. [DOI: 10.1160/th12-12-0928] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 03/11/2013] [Indexed: 12/17/2022]
Abstract
summaryClinical management of obese subjects to reduce their risk of suffering cardiovascular events is complex. Obese patients typically require preventive strategies, life-style modifications, and multi-drug therapy to address obesity-induced co-morbidities. Data regarding the effects of excess weight on the pharmacokinetics of most drugs is scarce as these individuals are often excluded from clinical trials. However, the physiological alterations observed in obese patients and their lower response to some antiplatelet agents and anticoagulants have suggested that dosage regimes need to be adjusted for these subjects. In this review we will briefly discuss platelet alterations that can contributeto increased thrombotic risk, analyse existing data regarding the effects of obesity on drug pharmacokinetics focusing on antiplatelet agents and anticoagulants, and we will describe the beneficial effects of weight loss on thrombosis.
Collapse
|
|
10
|
Abtan J, Silvain J, Kerneis M, O’Connor SA, Barthélémy O, Vignalou JB, Beygui F, Brugier D, Collet JP, Montalescot G. Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay. Thromb Haemost 2017; 110:1055-64. [DOI: 10.1160/th13-03-0203] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Accepted: 07/07/2013] [Indexed: 11/05/2022]
Abstract
SummaryA new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.
Collapse
|
|
11
|
Darlington A, Tello-Montoliu A, Rollini F, Ueno M, Ferreiro JL, Patel R, Desai B, Guzman L, Bass T, Angiolillo D. Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease. Thromb Haemost 2017; 111:258-65. [DOI: 10.1160/th13-07-0529] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 09/17/2013] [Indexed: 01/22/2023]
Abstract
SummaryIncreased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with highdose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m2] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m2 completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.
Collapse
|
|
12
|
Grove EL, Hossain R, Storey RF. Platelet function testing and prediction of procedural bleeding risk. Thromb Haemost 2017; 109:817-24. [DOI: 10.1160/th12-11-0806] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 02/16/2013] [Indexed: 11/05/2022]
Abstract
SummaryThe essential role of platelets in haemostasis underlies the relationship between platelet function and spontaneous or procedure-related bleeding, which has important prognostic implications. Although not routinely undertaken, platelet function testing offers the potential to tailor antiplatelet therapy for individual patients. However, uncertainties remain about how well platelet function testing may predict haemostasis and guide management of bleeding risk. Studies of aspirin, P2Y12 inhibitors and other antiplatelet drugs clearly demonstrate how inhibition of platelet function increases bleeding risk. More potent antiplatelet drugs are associated with higher bleeding rates, consistent with the levels of platelet inhibition achieved by these drugs. Studies of patients treated with clopidogrel, which is associated with wide inter-individual variation in antiplatelet effect, suggest that platelet function testing may predict bleeding risk related to coronary artery bypass grafting (CABG) surgery and potentially guide the timing of surgery following discontinuation of clopidogrel. Similarly, some studies have demonstrated a relationship between clopidogrel response and bleeding in patients undergoing percutaneous coronary intervention (PCI), although other studies have not supported this. Carriage of the *17 allele of cytochrome P450 2C19, which is associated with gain of function and enhanced response to clopidogrel, seems to be associated with increased bleeding risk, although studies showing lack of apparent effect of loss-of-function alleles provide contradictory evidence. Further large studies are needed to guide best practice in the application of platelet function testing in the clinical management of patients treated with antiplatelet drugs in order to optimise individual care.
Collapse
|
|
13
|
van der Meijden PEJ, Henskens YMC, ten Cate-Hoek AJ, Cate HT, Vries MJA. Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. Thromb Haemost 2017; 115:7-24. [DOI: 10.1160/th15-04-0355] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Accepted: 06/29/2015] [Indexed: 12/14/2022]
Abstract
SummaryPatients with coronary artery disease are usually treated with dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Patients on DAPT are at risk of both ischaemic and bleeding events. Although side-lined for a long time, real-life studies have shown that both the incidence and the associated morbidity and mortality of outof-hospital bleeding are high. This indicates that prevention of (postinterventional) bleeding is as important as prevention of ischaemia. For this purpose it is crucial to reliably identify patients with a high bleeding risk. In order to postulate an algorithm, which could help identifying these patients, we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding. We searched and appraised the following tools: platelet function tests, genetic tests, bleeding scores and questionnaires and haemostatic tests. Most studies indicated that low on-treatment platelet reactivity (LTPR), as measured by several platelet function tests, and the carriage of CYP2C19*17 allele were independent risk factors for bleeding. A bleeding score also proved to be helpful in identifying patients at risk. No studies on haemostatic tests were retrieved. Several patient characteristics were also identified as independent predictors of bleeding, such as older age, female sex and renal failure. Combining these risk factors we propose an algorithm that would hypothetically facilitate identification of those patients at highest risk, warranting prevention measures for bleeding. This could be a starting point for further research concerning the topic.
Collapse
|
|
14
|
Abstract
The pharmacological inhibition of platelets has always been regarded as a double-edged sword: the challenge of balancing the antithrombotic effect against the bleeding risk. Potent antiplatelet agents and novel oral anticoagulants, sometimes in combination, are increasingly used in the treatment of cardiovascular disease and for thromboprophylaxis in atrial fibrillation. Although such treatment has reduced the risk of thrombotic events, the potential for major bleeding has increased, and a technique to identify those at increased bleeding risk is greatly needed. Platelet function tests (PFTs), most frequently VerifyNow and also the vasodilator-stimulated phosphoprotein -phosphorylation assay, have been used to identify low on-treatment platelet reactivity, to identify individuals who may be at increased bleeding risk. Such results predict nuisance bleeding, but many individuals have low on-treatment platelet reactivity and yet do not exhibit major or even minor bleeding. Although PFTs may be useful in assessing populations, they do not allow identification of individual patients at risk of bleeding on either antiplatelet or novel oral anticoagulant therapy, nor do they allow the tailoring of such therapy to optimize the risk:benefit ratio. Thrombin plays a cardinal role in both arterial thrombus formation and hemostasis, yet most PFTs fail to assess the contribution of thrombin, because they employ anticoagulated blood. Techniques such as the calibrated automated thrombogram and the point-of-care global thrombosis test, performed on native blood, which measure endogenous thrombin potential, seem to show the most promise for profiling bleeding risk, as tests that most physiologically assess the effects of medications on thrombin.
Collapse
|
|
15
|
Sabouret P, Taiel-Sartral M, Chartier F, Akiki S, Cuisset T. Prasugrel Use in Real Life: A Report From the Outpatient Setting in France. Clin Cardiol 2016; 39:378-84. [PMID: 27299993 DOI: 10.1002/clc.22553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 04/15/2016] [Indexed: 12/19/2022] Open
Abstract
The objective of this study was to provide descriptive statistics on patterns of prasugrel usage in the outpatient setting in France. This retrospective study was conducted to describe treatment patterns for prasugrel in the outpatient setting in France using the Intercontinental Marketing Services (IMS) Disease Analyzer database, which collates electronic medical records updated by a nationally representative database of 1200 French general practitioners (GPs). Anonymous data were collected prospectively at each follow-up visit. The study population consisted of patients with ≥1 prescription for prasugrel in the outpatient setting from its launch date to 3 years post-launch. Patients were followed up from the date of the first prescription for prasugrel recorded in the database until they died, changed GP, or reached the end of the study, whichever came first. In France, the IMS Disease Analyzer included 1052 patients receiving ≥1 prescription of prasugrel from January 2010 until October 2012. Eighty-five percent of the population was male. The mean age was 58 years; 94.3% were age <75 years, and 95.0% weighed ≥60 kg. Of the total, 99.8% of patients were prescribed a daily maintenance dose of 10 mg, and 0.2% had a history of transient ischemic attack/stroke. Concomitant medications were antiplatelet agents (100%; aspirin, 93.7%), lipid-lowering agents (90.1%), β-blockers (83.7%), angiotensin-converting enzyme inhibitors (62.2%), and anti-ulcer medications (55.1%). The results reflect good usage of prasugrel by French GPs in the outpatient setting, with excellent implementation of the Prasugrel European Summary Product Characteristics.
Collapse
Affiliation(s)
- Pierre Sabouret
- ACTION Study Group, Heart Institute, Cardiology Department, Pitié-Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France
| | - Magali Taiel-Sartral
- Cardiovascular Unit, Health Outcome, Corporate Affairs Lilly France, Neuilly-sur-Seine, France
| | - Florence Chartier
- Cardiovascular Unit, Health Outcome, Corporate Affairs Lilly France, Neuilly-sur-Seine, France
| | - Sabine Akiki
- Cardiovascular Unit, Health Outcome, Corporate Affairs Lilly France, Neuilly-sur-Seine, France
| | - Thomas Cuisset
- Cardiology Department, Timone University Hospital, and Department of Medicine, Aix-Marseille University, Marseille, France
| |
Collapse
|
|
16
|
One-year incidence and clinical impact of bleeding events in patients treated with prasugrel or clopidogrel after ST-segment elevation myocardial infarction. Arch Cardiovasc Dis 2016; 109:337-47. [PMID: 27079469 DOI: 10.1016/j.acvd.2016.01.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 12/31/2015] [Accepted: 01/20/2016] [Indexed: 11/20/2022]
Abstract
BACKGROUND Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy. AIMS To evaluate the effect of bleedings for up to 12months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel. METHODS Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients. RESULTS A total of 390 patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P=0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P=0.03), and occurred more frequently with prasugrel (P=0.001). One-year mortality was very low (1.9 per 100 person-years, 95% confidence interval 0.9-4.0), and was higher in the clopidogrel group (P=0.03). CONCLUSIONS In this unselected STEMI population, the rate of major bleedings with prasugrel at 12months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication.
Collapse
|
|
17
|
Samoš M, Fedor M, Kovář F, Mokáň M, Bolek T, Galajda P, Kubisz P, Mokáň M. Type 2 Diabetes and ADP Receptor Blocker Therapy. J Diabetes Res 2015; 2016:6760710. [PMID: 26824047 PMCID: PMC4707344 DOI: 10.1155/2016/6760710] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 10/04/2015] [Indexed: 12/15/2022] Open
Abstract
Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy.
Collapse
Affiliation(s)
- Matej Samoš
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Marián Fedor
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - František Kovář
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Michal Mokáň
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Tomáš Bolek
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Peter Galajda
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Peter Kubisz
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| | - Marián Mokáň
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia
| |
Collapse
|
|
18
|
Bacquelin R, Oger E, Filippi E, Hacot JP, Auffret V, Le Guellec M, Coudert I, Castellant P, Moquet B, Druelles P, Rialan A, Rouault G, Boulanger B, Treuil J, Leurent G, Bedossa M, Boulmier D, Avez B, Gilard M, Le Breton H. Safety of prasugrel in real-world patients with ST-segment elevation myocardial infarction: 1-year results from a prospective observational study (Bleeding and Myocardial Infarction Study). Arch Cardiovasc Dis 2015; 109:31-8. [PMID: 26514325 DOI: 10.1016/j.acvd.2015.08.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 06/19/2015] [Accepted: 08/29/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Antiplatelet therapies, including prasugrel, are a cornerstone in the treatment of ST-segment elevation myocardial infarction (STEMI), but are associated with a bleeding risk. This risk has been evaluated in randomized trials, but few data on real-world patients are available. AIM To evaluate prasugrel safety in real-world patients with STEMI. METHODS Consecutive patients with STEMI were recruited over 1 year. Follow-up was done at 3 months and 1 year to evaluate prasugrel safety from hospital discharge to the STEMI anniversary date. The primary outcome was occurrence of any major bleeding according to the Bleeding Academic Research Consortium (BARC) 3 or 5 definitions, or minor bleeding according to the BARC 2 definition. RESULTS Overall, 1083 patients were recruited. Compared to patients treated with aspirin+clopidogrel, patients treated with aspirin+prasugrel had fewer BARC 3 or 5 bleedings (two [0.4%] patients vs. nine [1.8%] patients; P=0.04), but more BARC 2 bleedings (45 [9.3%] patients vs. 20 [4.0%] patients; P<0.001). The baseline characteristics of prasugrel- and clopidogrel-treated patients differed because the former were carefully selected (younger, higher body mass index, less frequent history of stroke). In the overall population, rates of in-hospital and out-of-hospital major bleeding were 2.6% (n=28) and 1.3% (n=13), respectively. CONCLUSION The rate of major bleeding, particularly out-of-hospital bleeding, in patients treated with prasugrel is low within 1 year after a STEMI. Accurate selection of patient candidates for prasugrel is likely to have reduced the risk of bleeding.
Collapse
Affiliation(s)
- Raoul Bacquelin
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France.
| | - Emmanuel Oger
- Rennes 1 University, LTSI, 35000 Rennes, France; Centre d'investigation clinique, INSERM CIC 0203, 35000 Rennes, France
| | | | | | - Vincent Auffret
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France
| | | | - Isabelle Coudert
- Emergency Service, Rennes University Hospital, 35000 Rennes, France
| | | | - Benoît Moquet
- Centre hospitalier Yves-Le-Foll, 22000 Saint-Brieuc, France
| | - Philippe Druelles
- Department of Cardiology, clinique Saint-Laurent, 35000 Rennes, France
| | - Antoine Rialan
- Centre hospitalier de Saint-Malo, 35400 Saint-Malo, France
| | - Gilles Rouault
- Centre hospitalier de Cornouaille, 29000 Quimper, France
| | | | - Josiane Treuil
- Emergency Service, Brest University Hospital, 29200 Brest, France
| | - Guillaume Leurent
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France
| | - Marc Bedossa
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France
| | - Dominique Boulmier
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France
| | - Bertrand Avez
- Centre hospitalier Yves-Le-Foll, 22000 Saint-Brieuc, France
| | - Martine Gilard
- Department of Cardiology, Brest University Hospital, 29200 Brest, France
| | - Hervé Le Breton
- Department of Cardiology, Rennes University Hospital, 35000 Rennes, France; Rennes 1 University, LTSI, 35000 Rennes, France; INSERM U1099, 35000 Rennes, France
| |
Collapse
|
|
19
|
Kerneis M, Silvain J, Abtan J, Hauguel M, Barthélémy O, Payot L, Brugier D, Galier S, Collet JP, Montalescot G. Platelet effect of prasugrel and ticagrelor in patients with ST-segment elevation myocardial infarction. Arch Cardiovasc Dis 2015; 108:502-10. [DOI: 10.1016/j.acvd.2015.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/17/2015] [Accepted: 04/15/2015] [Indexed: 11/26/2022]
|
|
20
|
Ticagrelor: a safe and effective approach for overcoming clopidogrel resistance in patients with stent thrombosis? Blood Coagul Fibrinolysis 2015; 27:117-20. [PMID: 26340464 DOI: 10.1097/mbc.0000000000000406] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Stent thrombosis is a morbid complication following percutaneous coronary intervention (PCI). Dual antiplatelet therapy significantly reduces stent thrombosis risk. However, the antiplatelet response to clopidogrel - the most frequently used ADP receptor antagonist in post-PCI patients - varies among individuals. High on-treatment platelet reactivity was repeatedly associated with the risk of stent thrombosis. Ticagrelor is a novel ADP receptor blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. This agent offers a unique mechanism of action, no relevant pharmacological interactions, consistent platelet inhibition, and a good safety profile. This article reviews the prospective use of ticagrelor in the treatment of stent thrombosis in acute coronary syndrome patients undergoing PCI of culprit coronary lesion.
Collapse
|
|
21
|
Vries MJA, van der Meijden PEJ, Henskens YMC, ten Cate-Hoek AJ, ten Cate H. Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. Thromb Haemost 2015. [DOI: 10.1160/th-15-04-0355] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
|
|
22
|
Alexopoulos D, Vogiatzi C, Stavrou K, Vlassopoulou N, Perperis A, Pentara I, Xanthopoulou I. Diabetes mellitus and platelet reactivity in patients under prasugrel or ticagrelor treatment: an observational study. Cardiovasc Diabetol 2015; 14:68. [PMID: 26025572 PMCID: PMC4453292 DOI: 10.1186/s12933-015-0232-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 05/23/2015] [Indexed: 01/17/2023] Open
Abstract
Background The influence of diabetes mellitus (DM) on platelet reactivity (PR) in prasugrel or ticagrelor treated patients is not well studied. Methods In an observational study involving 777 patients with acute coronary syndrome undergoing percutaneous coronary intervention treated by either prasugrel 10 mg od (n = 315) or ticagrelor 90 mg bid (n = 462), platelet function was assessed using the VerifyNow P2Y12 function assay (in PRU) at one month post intervention. Results In the overall population, ticagrelor and insulin-treated DM affected PR, with a decrease in log by 0.88 (corresponding to a 58 % decrease in PR) compared to prasugrel-treated patients (p < 0.001), and an increase in log by 0.26 (corresponding to a 30 % increase in PR) compared to non-diabetic patients (p = 0.01), respectively. PR in prasugrel-treated patients differed significantly by DM status: 70.0 (36.3-113.0) in non-diabetic vs 69.0 (44.5-115.3) in non insulin-treated diabetic vs 122.0 (69.0-161.0) in insulin-treated diabetic patients, p for trend = 0.01. No differences were observed in ticagrelor-treated patients. By multivariate analysis, in prasugrel-treated patients insulin-treated DM was the only factor predicting PR, with log of PR increased by 0.42 (corresponding to a 52 % increase in PR) compared to non-diabetic patients (p = 0.001). No factor was found to affect PR in ticagrelor-treated patients. Conclusions Patients with insulin-treated DM treated with prasugrel post PCI have higher PR, than patients without DM or non insulin-treated diabetic patients treated with this drug. Ticagrelor treated patients have overall lower PR than patients on prasugrel, independent of DM status or insulin treatment. Trial registration Clinical Trials Gov. NCT01774955
Collapse
Affiliation(s)
- Dimitrios Alexopoulos
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Chrysoula Vogiatzi
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Katerina Stavrou
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Niki Vlassopoulou
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Angelos Perperis
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Ioanna Pentara
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| | - Ioanna Xanthopoulou
- Department of Cardiology, Patras University Hospital, University of Patras, Rion, Patras, Greece.
| |
Collapse
|
|
23
|
Strisciuglio T, Di Gioia G, De Biase C, Esposito M, Franco D, Trimarco B, Barbato E. Genetically Determined Platelet Reactivity and Related Clinical Implications. High Blood Press Cardiovasc Prev 2015; 22:257-64. [PMID: 25986078 DOI: 10.1007/s40292-015-0104-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 05/12/2015] [Indexed: 01/06/2023] Open
Abstract
Many drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous coronary intervention with stent implantation. Primary targets are represented by enzymes or receptors involved in platelet activation. Genetic mutations in these targets contribute to the inter-individual variability in platelet responses therefore weakening the efficacy of antiplatelet agents. High on treatment platelet reactivity is a condition characterized by low levels of platelet inhibition despite the use of antiplatelet drugs. This could be responsible for re-infarction, stent-thrombosis and strokes, affecting short and long-term prognosis after coronary revascularization. So far, to test antiplatelet resistance either the assessment of platelet function or the identification of genetic carriers of poly morphisms have been pursued. Although several methods are now available to test platelet reactivity, it is still debated whether its routine assessment gives real benefits in clinical practice. The present review aims at examining current evidences on genetic polymorphisms affecting optimal platelet inhibition.
Collapse
Affiliation(s)
- Teresa Strisciuglio
- Divisione di Cardiologia, Dipartimento di Scienze Biomediche Avanzate, Università Federico II Napoli, Naples, Italy
| | | | | | | | | | | | | |
Collapse
|
|
24
|
Lee DH, Kim MH, Guo LZ, Park MK, Yi SJ. Lower loading dose of prasugrel compared with conventional loading doses of clopidogrel and prasugrel in korean patients undergoing elective coronary angiography: a randomized controlled study evaluating pharmacodynamic efficacy. Korean Circ J 2014; 44:386-93. [PMID: 25469140 PMCID: PMC4248610 DOI: 10.4070/kcj.2014.44.6.386] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 08/04/2014] [Accepted: 08/28/2014] [Indexed: 12/14/2022] Open
Abstract
Background and Objectives Although prasugrel allows for rapid and potent platelet inhibition, the efficacy and safety of lower doses of prasugrel for patients of East Asian ethnicity has not yet been investigated. We compared the effect of a lower loading dose (LD) of prasugrel with conventional LDs of clopidogrel and prasugrel in Korean patients. Subjects and Methods Forty-three Korean patients undergoing coronary angiography were enrolled in the study. Participants were randomly administered LDs of clopidogrel 600 mg, prasugrel 30 mg or prasugrel 60 mg prior to coronary angiography. Platelet reactivity was assessed at baseline and at the time of peak platelet inhibition using light transmission aggregometry (LTA), the VerifyNow assay, and multiple electrode aggregometry. Results Although baseline platelet reactivity between the groups showed no significant differences, at the time of peak platelet inhibition, the prasugrel 30 mg (18.9±10.0%) and 60 mg groups (13.8±10.8%) showed significantly more potent platelet inhibition than the clopidogrel 600 mg group (52.9±15.8%; p<0.001) by LTA. However, there were no significant differences between the prasugrel 30 mg and 60 mg groups (p=0.549). Conclusion The loading effect of prasugrel 30 mg was more potent than clopidogrel 600 mg and was not significantly different from prasugrel 60 mg.
Collapse
Affiliation(s)
- Dong Hyun Lee
- Department of Cardiology, Dong-A University Hospital, Busan, Korea
| | - Moo Hyun Kim
- Department of Cardiology, Dong-A University Hospital, Busan, Korea. ; Regional Clinical Trial Center, Dong-A University Hospital, Busan, Korea
| | - Long Zhe Guo
- Regional Clinical Trial Center, Dong-A University Hospital, Busan, Korea
| | - Min Kyu Park
- Regional Clinical Trial Center, Dong-A University Hospital, Busan, Korea
| | - So Jeong Yi
- Regional Clinical Trial Center, Dong-A University Hospital, Busan, Korea
| |
Collapse
|
|
25
|
Samoš M, Fedor M, Kovář F, Duraj L, Fedorová J, Galajda P, Staško J, Bolek T, Kubisz P, Mokáň M. Prasugrel loading dose in diabetic patients with acute STEMI - Always sufficiently effective? Observation in two cases and review of current knowledge. COR ET VASA 2014. [DOI: 10.1016/j.crvasa.2013.12.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
26
|
Platelet reactivity during ticagrelor maintenance therapy: a patient-level data meta-analysis. Am Heart J 2014; 168:530-6. [PMID: 25262263 DOI: 10.1016/j.ahj.2014.06.026] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 06/15/2014] [Indexed: 11/22/2022]
Abstract
BACKGROUND Factors associated with platelet reactivity (PR) during ticagrelor maintenance dose (MD) are not well defined. We aimed to examine factors that influence levels of PR during chronic ticagrelor therapy. METHODS We performed individual participant data meta-analysis of 445 patients from 8 studies who had PR assessment with the VerifyNow P2Y12 assay (Accumetrics, Inc, San Diego, CA) while on ticagrelor 90 mg twice a day MD for at least 14 days. RESULTS Distribution of PR during ticagrelor MD was highly skewed toward lower values. No case of high PR (≥230 P2Y12 reaction units [PRU]) was observed. Age and body mass index (BMI) positively affected PR, with every increase in decade and 5 units of BMI resulting in 7.9% and 4.1% increase in PR, respectively. Current smoking status negatively affected PR with 13.7% decrease in PR in current smokers, compared with nonsmokers. Low PR (LPR) was defined as the lowest quartile of PR values (<10 PRU). In multivariate analysis, diabetes mellitus and age >70 years were independently associated with lower probability for LPR with a relative risk (95% CIs) of 0.570 (0.361-0.899) and 0.554 (0.325-0.944), P = .016 and P = .030, respectively. CONCLUSIONS Age, BMI, and current smoking status affect PR during ticagrelor MD. Diabetes mellitus and age >70 years were found to be associated with lower probability for LPR. Further research is required to assess the clinical implications of these findings in ticagrelor-treated patients.
Collapse
|
|
27
|
Paniccia R, Priora R, Liotta AA, Maggini N, Abbate R. Assessment of platelet function: Laboratory and point-of-care methods. World J Transl Med 2014; 3:69-83. [DOI: 10.5528/wjtm.v3.i2.69] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 03/14/2014] [Accepted: 04/29/2014] [Indexed: 02/05/2023] Open
Abstract
In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. “Old” platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis in platelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.
Collapse
|
|
28
|
Janssen PW, ten Berg JM, Hackeng CM. The use of platelet function testing in PCI and CABG patients. Blood Rev 2014; 28:109-21. [DOI: 10.1016/j.blre.2014.03.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Accepted: 03/11/2014] [Indexed: 11/27/2022]
|
|
29
|
Abstract
Worldwide, cardiovascular events represent the major cause of morbidity and mortality. A key role in the pathogenesis of these events is played by platelets. Interventional procedures, with placement of coronary and vascular stents, often represent the preferred therapeutic strategy. Antiplatelet medications are considered first-line therapy in preventing cardiovascular thrombotic events. A wide array of antiplatelet agents is available, each with different pharmacological properties. When patients on antiplatelet agents present for surgery, the perioperative team must design an optimal strategy to manage antiplatelet medications. Each patient is stratified according to risk of developing a cardiovascular thrombotic event and inherent risk of surgical bleeding. After risk stratification analysis, various therapeutic pathways include continuing or discontinuing all antiplatelet agents or maintaining one antiplatelet agent and discontinuing the other. This review focuses on the pharmacological and pharmacokinetic properties of both older and novel antiplatelet drugs, and reviews current literature and guidelines addressing options for perioperative antiplatelet management.
Collapse
Affiliation(s)
- A D Oprea
- Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA
| | | |
Collapse
|
|
30
|
Samoš M, Šimonová R, Kovář F, Duraj L, Fedorová J, Galajda P, Staško J, Fedor M, Kubisz P, Mokáň M. Clopidogrel resistance in diabetic patient with acute myocardial infarction due to stent thrombosis. Am J Emerg Med 2014; 32:461-5. [PMID: 24560391 DOI: 10.1016/j.ajem.2014.01.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 01/11/2014] [Indexed: 11/26/2022] Open
Abstract
Stent thrombosis is a morbid complication after percutaneous coronary intervention. Dual antiplatelet therapy significantly reduces stent thrombosis risk and forms currently the basis in acute ST elevation myocardial infarction pharmacologic treatment. The introduction of clopidogrel has made a major advance in the acute coronary syndrome treatment. However, there is growing evidence about failure in antiplatelet response after clopidogrel, which may lead to subsequent risk of future thrombotic events. The antiplatelet inhibitory effect of clopidogrel varies widely among individuals. High on-treatment platelet reactivity has been repeatedly associated with a hazard for cardiovascular events, including stent thrombosis. Laboratory monitoring of antiplatelet therapy efficacy may help identify patients with insufficient antiplatelet response. Prasugrel therapy was repeatedly described as an effective method to overcome clopidogrel resistance. We report a case of diabetic patient in whom myocardial reinfarction due to stent thrombosis developed. Clopidogrel resistance was detected in this patient using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation assessment. After prasugrel administration, no other ischemic event occurred, and patient was released to outpatient care in good general condition.
Collapse
Affiliation(s)
- Matej Samoš
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
| | - Radoslava Šimonová
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Frantisek Kovář
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Lukas Duraj
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Jana Fedorová
- Hemomedika, Center of Thrombosis and Hemostasis, Martin, Slovak Republic
| | - Peter Galajda
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Jan Staško
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Marian Fedor
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Peter Kubisz
- National Center of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Marian Mokáň
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| |
Collapse
|
|
31
|
Mayer K, Orban M, Bernlochner I, Braun S, Schulz S, Gross L, Hadamitzky M, Schunkert H, Laugwitz KL, Massberg S, Kastrati A, Sibbing D. Predictors of antiplatelet response to prasugrel during maintenance treatment. Platelets 2014; 26:53-8. [DOI: 10.3109/09537104.2013.863857] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
|
|
32
|
Pankert M, Quilici J, Loundou AD, Verdier V, Lambert M, Deharo P, Bonnet G, Gaborit B, Morange PE, Valéro R, Dutour A, Bonnet JL, Alessi MC, Cuisset T. Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting. Am J Cardiol 2014; 113:54-9. [PMID: 24182762 DOI: 10.1016/j.amjcard.2013.09.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Revised: 09/24/2013] [Accepted: 09/24/2013] [Indexed: 12/30/2022]
Abstract
This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.
Collapse
Affiliation(s)
- Mathieu Pankert
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Jacques Quilici
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Anderson Diendonné Loundou
- Assistance Publique-Hôpitaux de Marseille-Unité d'Aide Méthodologique à la Recherche clinique, Marseille, France
| | - Valentine Verdier
- Assistance Publique-Hôpitaux de Marseille-Equipe Mobile d'Aide à l'Investigation, Marseille, France
| | - Marc Lambert
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Pierre Deharo
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Guillaume Bonnet
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Bénédicte Gaborit
- Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Pierre Emmanuel Morange
- Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Timone, Marseille, France
| | - René Valéro
- Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Département de Nutrition, Maladies Métaboliques, Endocrinologie, Centre Hospitalo-Universitaire Timone, Marseille, France
| | - Anne Dutour
- Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Jean-Louis Bonnet
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France
| | - Marie-Christine Alessi
- Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Timone, Marseille, France
| | - Thomas Cuisset
- Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
| |
Collapse
|
|
33
|
Silvain J, Kerneis M, Collet JP, Montalescot G. New Insights for Low Dosing With the New P2Y 12 Inhibitors. Circ J 2014; 78:2840-2. [DOI: 10.1253/circj.cj-14-1166] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Johanne Silvain
- Institut de Cardiologie, Pitié-Salpêtrière University Hospital
| | - Mathieu Kerneis
- Institut de Cardiologie, Pitié-Salpêtrière University Hospital
| | | | | | | |
Collapse
|
|
34
|
Park KH, Jeong MH, Lee KH, Sim DS, Yoon HJ, Yoon NS, Kim KH, Park HW, Hong YJ, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC. Comparison of peri-procedural platelet inhibition with prasugrel versus adjunctive cilostazol to dual anti-platelet therapy in patients with ST segment elevation myocardial infarction. J Cardiol 2013; 63:99-105. [PMID: 24012432 DOI: 10.1016/j.jjcc.2013.07.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 06/04/2013] [Accepted: 07/02/2013] [Indexed: 11/20/2022]
Abstract
BACKGROUND It has been well known that the inhibition of platelet aggregation (IPA) by anti-platelet agents was important to reduce the thrombo-embolic events in patients with ST segment elevation myocardial infarction (STEMI). However, the peri-procedural IPA by anti-platelet agents was not well known. METHODS We compared the peri-procedural IPA between prasugrel and adjunctive cilostazol to dual anti-platelet therapy (triple anti-platelet therapy; TAP) in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We prospectively randomized 70 consecutive clopidogrel-naive patients with STEMI planned PCI to either prasugrel [loading dose (LD) 60 mg; 37 patients] or TAP (LD aspirin 300 mg, clopidogrel 600 mg, and cilostazol 200mg; 33 patients). Primary end points of the study were the platelet reactivity unit (PRU) or % inhibition by the VerifyNow P2Y12 assay at pre-PCI and pre-discharge. RESULTS The drug loading to pre-PCI time was similar between prasugrel and TAP groups (25.4 ± 10.42 min vs. 25.5 ± 10.56 min, p=0.957). PRU at pre-PCI was significantly lower in prasugrel than in TAP (269.1 ± 71.69 vs. 306.5 ± 48.67, p=0.012). The lower PRU and greater % inhibition also observed in prasugrel than in TAP at pre-discharge (108.2 ± 60.51 vs. 238.1 ± 73.40; 63.6 ± 18.51% vs. 16.8 ± 17.91%, p<0.001 respectively). No differences in in-hospital bleeding complications between the two groups were observed. CONCLUSION Our study demonstrates that prasugrel could produce a significantly greater peri-procedural as well as in-hospital IPA compared with TAP in patients with STEMI undergoing primary PCI.
Collapse
Affiliation(s)
- Keun-Ho Park
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Myung Ho Jeong
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea.
| | - Ki Hong Lee
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Doo Sun Sim
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Hyun Ju Yoon
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Nam Sik Yoon
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Kye Hun Kim
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Hyung Wook Park
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Young Joon Hong
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Ju Han Kim
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Youngkeun Ahn
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Jeong Gwan Cho
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Jong Chun Park
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| | - Jung Chaee Kang
- The Heart Center of Chonnam National University Hospital, Gwangju, South Korea
| |
Collapse
|
|
35
|
Kerneis M, Silvain J, Abtan J, Cayla G, O'Connor SA, Barthélémy O, Vignalou JB, Beygui F, Brugier D, Martin R, Collet JP, Montalescot G. Switching Acute Coronary Syndrome Patients From Prasugrel to Clopidogrel. JACC Cardiovasc Interv 2013; 6:158-65. [DOI: 10.1016/j.jcin.2012.09.012] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 08/30/2012] [Accepted: 09/28/2012] [Indexed: 10/27/2022]
|