Prasugrel (Effient): Platelet activation and aggregation inhibitor approved to reduce the rate of thrombotic CV events in patients with ACS undergoing PCI

Prasugrel is a thienopyridine-class inhibitor of platelet activation and aggregation. This agent was approved on July 10, 2009, to reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI), including patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) and patients with ST-elevation myocardial infarction (STEMI) managed with primary or delayed PCI.

Efficacy. The efficacy of prasugrel was assessed in a multicenter, international, randomized, double-blind, parallel-group study that compared prasugrel with clopidogrel in patients with ACS who were undergoing PCI. The loading dose of prasugrel (60 mg) or clopidogrel (300 mg) was administered between randomization and 1 hour after patients left the catheterization laboratory. Patients were then treated with prasugrel 10 mg/d or clopidogrel 75 mg/d and followed up for ≥6 months. The primary outcome was the composite of CV death, nonfatal MI, or nonfatal stroke. This end point occurred less frequently in prasugrel-treated patients than in clopidogrel-treated patients in both the UA/NSTEMI group (RR reduction, 18.0%; 95% CI, 7.3%–27.4%; P=.002) and the STEMI group (RR reduction, 20.7%; 95% CI, 3.2%–35.1%; P=.019). In both groups, this reduction in the composite end point was driven by a reduction in nonfatal MI. Prasugrel was associated with a higher rate of clinically significant bleeding than clopidogrel.

Safety. Treatment with prasugrel increases a patient's risk of bleeding. Bleeding should be suspected in patients who are hypotensive and have recently undergone coronary angiography, PCI, coronary artery bypass grafting (CABG), or another surgical procedure, even if no overt signs of bleeding are present. Prasugrel should not be used in patients with active bleeding or history of transient ischemic attack (TIA) or stroke. Additional risk factors for bleeding include age ≥75 years, CABG or other surgical procedure, body weight <60 kg, propensity for bleeding, and medications that increase bleeding risk. Prasugrel should be discontinued ≥7 days before CABG when possible. Prasugrel should be discontinued in the event of active bleeding, elective surgery, stroke, or TIA. Premature discontinuation of prasugrel is associated with increased risk of cardiac events; therefore, lapses in therapy should be avoided. Patients treated with other thienopyridines have experienced thrombotic thrombocytopenic purpura. The most common adverse events associated with prasugrel treatment include bleeding, severe thrombocytopenia, anemia, abnormal hepatic function, allergic reactions, angioedema, hypertension, hypercholesterolemia/hyperlipidemia, and headache.

Dosing. Prasugrel therapy should be initiated as a single 60-mg oral loading dose; therapy should then be continued at a dose of 10 mg/d. Prasugrel-treated patients should also receive aspirin 75 to 325 mg/d. For patients who weigh <60 kg, healthcare professionals should consider lowering the maintenance dose of prasugrel to 5 mg/d.