Prasugrel vs. Clopidogrel: A Split Decision

Several studies have established the efficacy of dual antiplatelet therapy with aspirin and clopidogrel for preventing atherothrombosis in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. Prasugrel, a new thienopyridine not yet on the market, is structurally similar to clopidogrel but has a more rapid onset of action and greater potency. Both drugs inhibit a platelet adenosine diphosphate receptor and require liver cytochrome reactions for activation.

In the manufacturer-sponsored, randomized, double-blind TRITON–TIMI 38 study, investigators compared prasugrel (loading dose, 60 mg; maintenance dose, 10 mg) with clopidogrel (300 mg and 75 mg, respectively) in 13,608 moderate- and high-risk ACS patients (10,074 with unstable angina or non–ST-segment-elevation MI and 3534 with ST-segment-elevation MI) undergoing PCI. All patients also received aspirin. The primary efficacy endpoint was the composite of cardiovascular death, nonfatal MI, and nonfatal stroke. Therapy lasted a median of 14.5 months.

With regard to the primary endpoint, the results favored prasugrel (9.9% vs. 12.1% with clopidogrel; hazard ratio, 0.81; 95% confidence interval, 0.73–0.90). This benefit was largely due to the difference in nonfatal MI incidence and appeared to attenuate with increasing patient age. However, prasugrel conferred significantly greater risks for major bleeding (2.4% vs. 1.8% with clopidogrel; HR, 1.32) and for life-threatening bleeding (1.4% vs. 0.9% with clopidogrel; HR, 1.52). The rates of serious adverse events unrelated to bleeding were similar in the two groups. According to these findings, for every 1000 patients treated with prasugrel rather than clopidogrel, 23 MIs were prevented and 6 major hemorrhages occurred.