by Bruce Sylvester – Investigators from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage AcuteCoronary Syndromes (TRILOGY ACS) study reported at ESC 2012 no significant difference between prasugrel and clopidogrel in the prevention of death, myocardial infarction or stroke among patients with acute coronary syndromes managed medically without revascularization.
TRILOGY ACS was double-blind, randomised trial. Researchers evaluated prasugrel (10 mg daily) compared with that of clopidogrel (75 mg daily) for up to 30 months of treatment in ACS patients under 75 years of age with unstable angina or non-ST elevation myocardial infarction (non-STEMI), managed without revascularisation.
Lead investigator, E. Magnus Ohman, Professor of Medicine, Associate Director, Duke Heart Center – Cardiology Clinics, Duke University Medical Center, Durham, North Carolina said that about 60% of ACS patients undergo revascularisation, but the remaining 40% are managed only with drug therapy. “Patients who are medically managed are at higher risk for repeated cardiovascular-related events,” said Professor Ohman. “So optimising medical therapy for these patients is extremely important.”
Ohman and his colleagues enrolled 7243 subjects from 52 countries. All took aspirin as background therapy. Prasugrel dose was reduced to 5 mg daily for patients weighing less than 60 kilograms.
The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke.
Ohman reported that, with median follow-up of 17 months, the primary end point among participants under 75 years occurred in 13.9% of those treated with prasugrel and 16.0% of those treated with clopidogrel (HR 0.91; 95% CI 0.79-1.05; P=0.21). The difference was not statistically significant.
Notably, the investigators found a time-dependent treatment effect with a trend for a lower risk of ischaemic events with prasugrel after 12 months among patients under 75 years of age. A pre-specified analysis accounting for all multiple recurrent ischemic events (not just the first event among all components of the primary end point) suggested a lower risk with prasugrel (HR 0.85; 95% CI 0.72-1.00; P=0.044).
The rates of major, life-threatening, fatal and intracranial bleeding were infrequent and similar in each treatment group, as was the frequency of non-hemorrhagic serious adverse events, except for a higher rate of heart failure in the clopidogrel group.
“This trial is unique in that it studied a population we have not previously explored in such detail,” said Ohman. “The result being neutral raises many important questions. The fact that prasugrel appears safe – with no statistical increase in major bleeding – offers assurance of the prolonged safety of this therapy, which had been raised in previous trials.”
TRILOGY ACS was funded by Eli Lilly and Daiichi Sankyo.