Prasugrel versus clopidogrel in patients with ACS

Prasugrel may not improve outcomes for patients under the age of 75 years with unstable angina or non-ST-segment elevation myocardial infarction who have not undergone revascularization, according to a study published in the New England Journal of Medicine.

This high-risk patient population has been underrepresented in large-scale studies, the authors acknowledge, and prasugrel has demonstrated benefits over clopidogrel in previous studies. Therefore, the researchers, led by Matthew T. Roe, MD, MHS, of Duke University in Durham, NC, sought to evaluate whether aspirin plus prasugrel was superior to aspirin plus clopidogrel for long-term therapy in these patients.

Patients were randomly assigned to receive aspirin plus either prasugrel or clopidogrel. In the researchers’ primary analysis, they evaluated a 10-mg daily dose of prasugrel versus a 75-mg daily dose of clopidogrel up to 30 months in patients aged 75 years and younger. The primary end point included death from cardiovascular causes, myocardial infarction, or stroke.

Although one might expect more intense platelet inhibition to reduce the rate of adverse outcomes, the researchers observed similar risks of bleeding and no significant reduction in cardiovascular events among patients.

They noted a 13.9% rate in the primary end point at a median 17-month follow-up point for patients taking prasugrel and a 16% rate in patients taking clopidogrel. They found no significant between-group difference in the rate of major cardiovascular events. Although they did observe higher rates of minor or moderate bleeding among patients receiving prasugrel, there was no significant increase in the rate of severe, major, or life-threatening bleeding despite treatment for up to 30 months. They did note a higher frequency for heart failure in patients taking clopidogrel.

“Prasugrel was not shown to be superior to clopidogrel for reducing the primary end point during 2.5 years of follow-up after a coronary event in patients receiving medical therapy without planned revascularization, even though signs of intensified platelet inhibition were observed in the prasugrel group,” the authors concluded. “The optimal treatment duration and intensity of P2Y12 inhibition after a coronary event for patients who do not undergo revascularization remain uncertain.”

The study was funded by Eli Lilly and Daiichi Sankyo.