Prasugrel (Effient) was not superior to clopidogrel (Plavix) for reducing the rate of major cardiovascular events in patients with acute coronary syndrome (ACS) who do not undergo revascularization, according to TRILOGY ACS results. While patients in the prasugrel group had higher rates of minor and moderate bleeding, there was no significant increase in the rate of severe, major or life-threatening bleeding.

The results were simultaneously presented Aug. 26 at the European Society of Cardiology Scientific Sessions in Munich and published online in the New England Journal of Medicine.

TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) was developed as a follow-up study to TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel). TRITON compared prasugrel with clopidogrel as a dual-antiplatelet therapy (DAPT) for patients with ACS and planned PCI. TRITON results showed benefit of using prasugrel in a DAPT, despite its higher rate of bleeding events.

TRILOGY ACS is a randomized, double-blind phase III trial designed to evaluate the superiority of aspirin plus prasugrel compared with aspirin plus clopidogrel as a long-term therapy for patients with unstable angina or MI without ST-segment elevation who do not undergo revascularization. The study enrolled 7,243 patients at 966 sites in 52 countries between 2008 and 2011. They were randomized to either an aspirin plus prasugrel (10 mg daily and 5 mg daily for patients weighing less than 60 kg) group or an aspirin plus clopidogrel (75 mg daily) group for up to 30 months of treatment.

Patients in the primary analysis were younger than 75. In a secondary analysis, 2,083 patients were 75 years or older and received 5 mg of prasugrel daily vs. clopidogrel 75 mg daily. The median follow-up was 17 months, with a primary efficacy endpoint in the under 75 group of composite of death from cardiovascular causes, nonfatal MI or nonfatal stroke. Secondary endpoints included suspected ischemic and bleeding events.

Matthew T. Roe, MD, of the Duke Clinical Research Institute in Durham, N.C., and colleagues found that baseline characteristics were balanced between the two prasugrel and clopidigrel study groups and among the overall population. The primary endpoint occurred in 13.9 percent of patients treated with prasugrel vs. 16 percent of those treated with clopidogrel, which was considered a no significant between-group difference. But while the frequency of the primary endpoint was similar between the two groups through 12 months, it trended toward a reduced risk in the prasugrel group after 12 months.

Key bleeding events, including the rates of severe, major and life-threatening bleeding, were similar between the two groups at 30 months in patients under 75. In contrast, in TRITON the rate of bleeding events was 2.4 percent in the prasugrel group vs. 1.8 percent in the clopidigrel group.

“Because we modified the prasugrel dose for patients with a higher risk of bleeding, we observed that prasugrel is as safe as clopidogrel with long-term treatment,” E. Magnus Ohman, MD, a professor of medicine at Duke and chairman of the TRILOGY ACS study, said in a release.

Additionally, in TRILOGY ACS there was no significant difference in the frequency of new, nonbenign neoplasms in the overall group.

“Prasugrel was not shown to be superior to clopidigrel for reducing the primary endpoint 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,” Roe and colleagues wrote.

But the lower risk of recurrent adverse events with prasugrel observed after 12 months of treatment had not been observed in previous studies, according to Ohman. “We believe further exploration of this finding is needed,” he said.

The authors wrote that optimal treatment duration and intensity for thienopyridine inhibitors of the P2Y12 receptor for ACS patients who do not undergo revascularization are still unknown. “[O]ur findings highlight the need for further study of differences in the response to intensified platelet inhibition for patients receiving medical therapy without revascularization, as compared with those undergoing catheterization, for treatment of an index cardiac event,” they concluded.

TRILOGY ACS was sponsored by Eli Lilly and Daiichi Sankyo.