Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment , to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention.

To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned

13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled

percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose

and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a

75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point

was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal

stroke. The key safety end point was major bleeding.

The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel

and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel,

0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant

reductions in the prasugrel group in the rates of myocardial infarction (9.7% for

clopidogrel vs. 7.4% for prasugrel; P<0.001),urgent target-vessel revascularization

(3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding

was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients

receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P = 0.03). Also greater

in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%;

P = 0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P = 0.23)

and fatal bleeding (0.4% vs. 0.1%; P = 0.002).

In patients with acute coronary syndromes with scheduled percutaneous coronary

intervention, prasugrel therapy was associated with significantly reduced rates of

ischemic events, including stent thrombosis, but with an increased risk of major

bleeding, including fatal bleeding. Overall mortality did not differ significantly

between treatment groups. (ClinicalTrials.gov number, NCT00097591.)

Source: N ENGL J Med 357;20 November 15, 2007