Thienopyridines in Acute Coronary Syndrome

Abstract

OBJECTIVE: To evaluate the safety and efficacy of the thienopyridines in order to identify their current place in therapy for the treatment of acute coronary syndrome (ACS). DATA SOURCES: Literature was accessed through MEDLINE (1966-October 2010 week 1), EMBASE (1980–2010 week 40), and a bibliographic review of published articles using the search terms acute coronary syndrome, clopidogrel, and prasugrel. Articles were limited to clinical trials conducted in humans and published in the English language. STUDY SELECTION AND DATA EXTRACTION: Head-to-head clinical trials evaluating the safety and efficacy of the thienopyridines in patients with ACS were critically reviewed. Trials evaluating ticlopidine were excluded due to its limited clinical use. DATA SYNTHESIS: Thienopyridines are an integral part of the treatment of ACS. Prior to the approval of prasugrel, clopidogrel was considered the agent of choice due to safety concerns associated with ticlopidine. A randomized controlled trial comparing prasugrel and clopidogrel has demonstrated superior efficacy with prasugrel, and post hoc analyses suggest additional benefit with prasugrel is derived in patients with ST-segment elevation myocardial infarction and patients with diabetes. However, safety concerns exist linking prasugrel with an increased risk of bleeding, which diminishes its advantage in elderly patients, underweight patients, and those with a history of stroke. Pharmacokinetic and pharmacodynamic studies discussing differences in response variability, platelet inhibition, interactions with proton pump inhibitors, and genetic factors between the thienopyridines are numerous, although more clinical data are needed to determine clinical implications. CONCLUSIONS: Clinical trial data have suggested prasugrel is superior to clopidogrel at preventing ischemic events in patients with ACS undergoing percutaneous coronary intervention. However, this coincides with an increased risk of bleeding. Clinicians must carefully interpret the current evidence, including limitations in study design and pharmacologic differences between agents, in order to balance the risks and benefits as new data become available.