• Coronary Artery Disease
• Cardiology Clinical Trials

In the largest trial to date of patients with medically managed acute coronary syndrome (ACS) without revascularization, prasugrel did not improve outcomes, compared with clopidogrel during 2.5 years of follow-up among patients <75 years. The findings are from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes [TRILOGY ACS] study, which was published to coincide with its presentation at the European Society of Cardiology Congress [Roe MT et al. N Engl J Med 2012].

The TRILOGY ACS trial is important because 40% to 60% of patients with ACS are managed without revascularization, said Matthew T. Roe, MD, MHS, Duke University Medical Center, Durham, North Carolina, USA. These patients are at high risk for subsequent complications, with rates of ischemic events 2-fold greater than those treated with revascularization. The investigators had hypothesized that prasugrel would be a better option than clopidogrel in patients with medically managed ACS, based on the superiority of prasugrel over clopidogrel in patients with ACS who underwent percutaneous revascularization in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction [TRITON-TIMI 38] trial [Wiviott SD et al. N Engl J Med 2007].

TRILOGY was an international trial that enrolled 9326 patients who were treated medically for unstable angina or non-ST-segment elevated myocardial infarction (NSTEMI). Patients were randomly assigned to treatment with prasugrel (10 mg QD) or clopidogrel (75 mg QD); the dose of prasugrel was reduced to 5 mg QD for patients weighing <60 kg. All patients also received aspirin as part of medical management. The primary analysis involved 7243 of the patients who were <75 years. A secondary, exploratory analysis was performed in 2083 patients who were ≥75 years, who were randomly assigned to prasugrel 5 mg QD or clopidogrel 75 mg QD. The primary endpoint was a composite of cardiovascular death, MI, or stroke. Patients were followed for as long as 30 months.

Dr. Roe reported the findings for the patients <75 years and for the overall population. At a median follow-up of 17 months for the younger patients, the rates of the primary composite endpoint were 13.9% in the group randomized to prasugrel and 16.0% in the clopidogrel group (HR, 0.91; 95% CI, 0.79 to 1.05; p=0.21). The results were similar for the overall patient population (18.7% vs 20.3%; HR, 0.96; 95% CI, 0.86 to 1.07; p=0.45).

Among patients <75 years, rates of bleeding were assessed according to the Global Use of Strategies to Open Occluded coronary arteries (GUSTO) and Thrombolysis in Myocardial Infarction (TIMI) criteria. Bleeding was low in both treatment groups, with no significant differences except for TIMI major or minor bleeding (1.8% in the prasugrel group vs 1.3% in the clopidogrel group; p=0.02). For the overall population, the rates of TIMI major bleeding were similar with prasugrel compared with clopidogrel (2.5% vs 1.8%; HR, 1.23; 95% CI, 0.84 to 1.81; p=0.29).

Dr. Roe noted that despite the absence of a significant benefit in the primary endpoint, the findings of a prespecified analysis suggested that prasugrel was associated with a lower risk of multiple recurrent ischemic events (not just the first event among all components of the primary endpoint [HR, 0.85; 95% CI, 0.72 to 1.00; p=0.04]) as well as a trend towards a lower risk of ischemic events after 12 months (HR for >12 months, 0.64; 95% CI, 0.48 to 0.86; p=0.02).

Though TRILOGY ACS failed to meet its primary endpoint, it contributes to the knowledge base about ACS patients who are medically managed. Additional analyses and studies will be needed to try to evaluate the role of prasugrel in the management of NSTEMI.

• © 2012 MD Conference Express®