Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes

Wiviott, Stephen D.; Braunwald, Eugene; McCabe, Carolyn H.; Montalescot, Gilles; Rużyłło, Witold; Gottlieb, Shmuel; Neumann, F.-J.; Ardissino, Diego; Servi, Stefano De; Murphy, Sabina A.; Riesmeyer, Jeffrey S.; Weerakkody, Govinda J.; Gibson, C. Michael; Antman, Elliott M.

doi:10.1056/nejmoa0706482

Cited by 6,064 publications

(4,838 citation statements)

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“…Clopidogrel remains the most widely used P2Y 12 inhibitor. Incremental benefit compared with clopidogrel has been shown with the more potent P2Y 12 inhibitors, prasugrel and ticagrelor, although at the risk of increased noncoronary artery bypass graft (CABG)‐related major bleeding 6, 7. Guidelines of the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC) for patients with non‐ST‐elevation (NSTE)‐ACS and ST‐elevation myocardial infarction (STEMI) recommend the use of ticagrelor or prasugrel over clopidogrel for patients with ACS undergoing PCI who can take these drugs safely 2, 3, 4, 5.…”

Section: Introductionmentioning

confidence: 99%

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

Larmore

Effron

Molife

et al. 2015

Cathet Cardio Intervent

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ObjectivesThe 30‐day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).BackgroundPrasugrel and ticagrelor demonstrated superior efficacy with increased non‐coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor.MethodsPatients hospitalized for ACS‐PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30‐day net adverse clinical events (NACE) in prasugrel‐ and ticagrelor‐treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding.ResultsData were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel‐treated patients were younger with fewer comorbidities than ticagrelor‐treated patients, and 30‐day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel‐treated than in ticagrelor‐treated patients (RR, 0.78; 95% CI, 0.64–0.94). A 30‐day adjusted MACE (RR, 0.80; 95% CI, 0.64–0.98) and major bleeding (RR, 0.65; 95% CI, 0.45–0.95) were also lower in prasugrel‐treated patients compared with ticagrelor‐treated patients.ConclusionsIn this “real‐world,” retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS‐PCI patients. © 2015 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

Larmore

Effron

Molife

et al. 2015

Cathet Cardio Intervent

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“…Prasugrel and clopidogrel are thienopyridine derivatives with adenosine diphosphate (ADP)–antagonistic activity and are widely used in clinics for the prevention of ischemic events in patients with ST‐segment‐elevated and non‐ST‐segment‐elevated myocardial infarction (STEMI and NSTEMI, respectively) who are undergoing percutaneous coronary intervention (PCI) 1, 2, 3. Rapid, potent, and consistent inhibition of platelet aggregation is important in patients with acute STEMI undergoing PCI 4, 5.…”

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confidence: 99%

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Umemura

Iwaki

2016

Clinical Pharm in Drug Dev

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The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2‐week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and Cmax of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor‐metabolizer subjects than in the extensive‐metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel.

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“…The negative association between increasing age and P2Y 12 inhibitor intensification may reflect clinician wariness of bleeding with higher‐potency P2Y 12 inhibitor use in older patients, as seen in the pivotal clinical trials evaluating these agents 7. Bleeding risk is likely further exacerbated by extending antiplatelet treatment duration as a result of the recurrent ischemic event 22, 23.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with clopidogrel, the higher‐potency P2Y 12 inhibitors, ticagrelor and prasugrel, reduce the incidence of recurrent cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI), but uptake of these agents into clinical practice in the United States has been tempered by concerns about increased bleeding risk and higher out‐of‐pocket patient costs 5, 6, 7, 8…”

mentioning

confidence: 99%

Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study

Kaltenbach

Peterson

Akhter

et al. 2018

JAHA

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BackgroundGuidelines recommend P2Y12 inhibitor therapy for 1 year after myocardial infarction (MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y12 inhibitor type among patients with recurrent ischemic events in the first year after MI.Methods and ResultsThe TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th–75th percentiles, 55–287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel‐treated patients led to P2Y12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification.ConclusionsFew patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

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Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes

Cited by 6,064 publications

References 35 publications

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study

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