Prasugrel Versus Clopidogrel for Acute Coronary Syndromes Without Revascularization

Study Questions:

What is the efficacy of prasugrel versus clopidogrel for long-term therapy in patients with acute coronary syndrome (ACS) without ST-segment elevation and who do not undergo revascularization?

Methods:

In the TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) double-blind, randomized trial, in a primary analysis involving 7,243 patients under the age of 75 years receiving aspirin, the investigators evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2,083 patients 75 years of age or older, they evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. Testing for the superiority of prasugrel over clopidogrel was done with a two-sided log-rank test and stratified according to clopidogrel status at the time of randomization.

Results:

At a median follow-up of 17 months, the primary endpoint of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio [HR] in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79-1.05; p = 0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary endpoint) suggested a lower risk for prasugrel among patients under the age of 75 years (HR, 0.85; 95% CI, 0.72-1.00; p = 0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group.

Conclusions:

The authors concluded that among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary endpoint, as compared with clopidogrel.

Perspective:

In this trial of prolonged treatment with prasugrel, as compared with clopidogrel, in ACS patients without ST-segment elevation who did not undergo revascularization, there was no reduction in the rate of major cardiovascular events in the prasugrel group. The more intense platelet inhibition with prasugrel was confirmed by the observation of higher rates of minor or moderate bleeding among patients receiving prasugrel, although there was no significant increase in the rate of severe, major, or life-threatening bleeding. These findings highlight the need for additional research into differences in the response to intensified platelet inhibition for patients receiving medical therapy without revascularization, as compared with those undergoing revascularization, for treatment of an index acute cardiac event.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Platelet Aggregation Inhibitors, Heart Failure


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