September 6, 2012 — Daiichi Sankyo Co. Ltd. and Eli Lilly and Co. announced data from the TRILOGY ACS study, a phase III trial comparing prasugrel plus aspirin to clopidogrel plus aspirin in patients with unstable angina (UA) or non-ST elevation myocardial infarction (NSTEMI), who were managed medically without an artery-opening procedure.
At 30 months, 13.9 percent of prasugrel patients vs. 16 percent of clopidogrel patients experienced the combined primary endpoint of heart attack, stroke or cardiovascular (CV) death in patients less than 75 years of age, the primary analysis population (HR=0.91; 95 percent CI: 0.79-1.05). This outcome was not statistically significant (P=0.21). Different from other large-scale trials, TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to edicallY manage Acute Coronary Syndromes) prospectively studied only the UA/NSTEMI population medically managed without revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery). Results of this study were published in the New England Journal of Medicine and also presented during a late-breaking session at the European Society of Cardiology (ESC) Congress 2012 in Munich, Germany.
From a safety perspective, TRILOGY ACS showed that rates of TIMI major bleeding events (including life-threatening or fatal bleeds) did not differ significantly between the prasugrel plus aspirin and clopidogrel plus aspirin treatment groups in patients less than 75 years of age or in the overall study population. In patients under age 75, non-CABG TIMI major bleeding occurred in 2.1 percent of prasugrel patients versus 1.5 percent of clopidogrel patients (HR=1.31, 95 percent CI: 0.81-2.11, P=0.27). However, the rates of TIMI major or minor bleeding were higher in patients treated with prasugrel (3.3 percent of prasugrel patients versus 2.1 percent of clopidogrel patients; HR=1.54; 95 percent CI: 1.06-2.23; P=0.02).
"TRILOGY ACS was designed to evaluate dual oral antiplatelet therapy in UA/NSTEMI patients who are managed medically without revascularization," said E. Magnus Ohman, M.D., Duke Clinical Research Institute and Chairperson of the TRILOGY ACS trial. "While the study did not demonstrate prasugrel was superior to clopidogrel in these patients, TRILOGY ACS provided some additional observations in this previously understudied population. The delayed treatment effect beyond 12 months observed in TRILOGY ACS had not been seen in earlier studies of shorter duration."
An analysis performed to account for multiple recurrent ischemic events suggested a lower risk among participants less than 75 years old treated with prasugrel (HR=0.85; 95 percent CI: 0.72–1.00; P=0.044).
A post-hoc exploratory analysis observed a trend for a lower risk in heart attack, stroke and death among patients treated with prasugrel beyond one year; HRs and 95 percent CIs for the time period of <12 months versus the time period of >12 months comparing prasugrel versus clopidogrel for the primary efficacy endpoint were 0.99 (0.84-1.16) versus 0.72 (0.54-0.97) (interaction P=0.07).
"Large-scale clinical trials in understudied populations, such as TRILOGY ACS, are important regardless of the result because they generate a sizeable amount of information for the medical community," said J. Anthony Ware, M.D., group vice president and cardiovascular/acute care platform leader, Eli Lilly and Co. "We look forward to presenting additional data from the platelet function sub-study, analyses of the elderly population data, as well as genomics information in future peer-reviewed forums."
"While this is not the outcome we anticipated, we believe this study contributes to the knowledge base about ACS patients who are medically managed," said Glenn Gormley, M.D., Ph.D., global head of R&D and senior executive officer at Daiichi Sankyo Co. Ltd. "The group of patients in the TRILOGY ACS trial is different from those who participated in the prior TRITON-TIMI 38 trial, where almost all ACS patients underwent percutaneous intervention."
The TRILOGY ACS study was conducted by Daiichi Sankyo and Eli Lilly and Co. in conjunction with the Duke Clinical Research Institute, one of the world's leading academic clinical research organizations and a part of Duke University Medical Center in Durham, N.C.
For more information: http://clinicaltrials.gov/ct2/show/NCT00699998