The potential role of prasugrel in secondary prevention of ischemic events in patients with acute coronary syndromes.

Acute coronary syndromes (ACS) are life-threatening manifestations of coronary artery disease, occurring when a thrombus forms at the site of atherosclerotic plaque rupture or fissuring. Almost all patients discharged from the hospital after an ACS (myocardial infarction or unstable angina) in the United States receive antiplatelet therapy. Current recommendations for post-ACS antiplatelet therapy are aspirin 75 to 162 mg/day indefinitely for all patients, plus a thienopyridine (currently clopidogrel 75 mg/day) for > or = 12 months in those receiving stents unless there is a high risk of bleeding. Dual antiplatelet therapy is indicated because patients with ACS have a hypercoagulable state which persists for at least 6 months after the acute event, and agents targeting different mechanisms have synergistic antiplatelet effects. The thienopyridine class includes ticlopidine, clopidogrel, and prasugrel. Clopidogrel is recommended in guidelines because ticlopidine carries a higher risk of adverse events including blood dyscrasias. Prasugrel is not yet available outside of a research setting. Clopidogrel + aspirin reduces the risk of an adverse clinical event after ACS by 15% and after percutaneous coronary intervention (PCI) by 34%. However, there is considerable interpatient variability in response to clopidogrel and a mean of 21% of patients (95% confidence interval [CI], 17 % - 25%) are nonresponsive to the drug as measured by platelet aggregation inhibition. Nonresponsiveness is associated with an increased risk of secondary ischemic events. Compared with clopidogrel, the newest thienopyridine, prasugrel, has a faster onset of platelet inhibition and less variability of response. In clinical trials, the combination of prasugrel + aspirin reduced the risk of a second ischemic event by 19% compared with clopidogrel + aspirin. There is a small increase in the risk of bleeding with dual antiplatelet therapy, but the benefit still outweighs the risk in most patients. Patients with a history of transient ischemic attack or stroke should not receive prasugrel + aspirin because of increased risk of events.