An analysis of TRITON-TIMI 38, based on the 12 month recommended length of therapy in the European label for prasugrel

Abstract

Background:In TRITON-TIMI 38, patients with acute coronary syndromes were treated with prasugrel or clopidogrel, with aspirin, for a median of 14.5 (maximum of 15) months. Based on this trial, the EU label for prasugrel recommends treatment for up to 12 months and excludes patients with prior stroke/transient ischemic attack (TIA). Furthermore, the EU label recommends the 10 mg maintenance dose (MD) for patients with body weight ≥60 kg and age <75 years. A lower MD of 5 mg is recommended for those with body weight <60 kg; although generally not recommended, 5 mg can be prescribed to patients ≥75 years after individual risk–benefit evaluation. This paper presents the one-year outcome data for this ‘10 mg indicated cohort’.Methods and results:From the overall cohort of 13,608 patients in TRITON-TIMI 38, 10,804 fulfilled inclusion criteria for the 10 mg indicated cohort, of whom 22% had a history of diabetes, 73% an index diagnosis of unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI), and 27% an index diagnosis of ST-segment-elevation myocardial infarction (STEMI). In this cohort at 12 months, those given prasugrel experienced significantly fewer ischemic events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, 7.8% vs 10.5%, hazard ratio (HR) = 0.73, p < 0.001, than those given clopidogrel, with a non-significant increase in non-coronary artery bypass graft (CABG) TIMI major bleeding, 1.7% vs 1.5%, HR = 1.15, p = 0.40; similarly, in the overall cohort these frequencies were 9.4% vs 11.4%, HR = 0.81, p < 0.001, for cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, and 2.2% vs 1.8%, HR = 1.24, p = 0.10, for non-CABG TIMI major bleeding. There was a significant reduction in stent thrombosis in the prasugrel group, with similar mortality rates and no excess of strokes.Conclusions:Treatment with prasugrel according to EU label recommendations results in a significant 27% and 57% relative risk reduction (absolute risk reductions of 2.7% and 1.2%) in ischemic events and stent thromboses respectively compared with clopidogrel, with a 15% relative risk increase (absolute risk increase of 0.2%) for major bleeds (p = 0.40), and no excess of strokes.Limitations:Although restricted to 365 days of follow-up, this analysis encapsulates 1366 of 1424 (95.9%) of all primary endpoint events and 244 of 257 (94.9%) of all first non-CABG TIMI major bleeds reported in the pivotal manuscript. Furthermore, the 10 mg indicated cohort was not a pre-specified subgroup in the study protocol, but due to European labeling restrictions, results for all outcomes in this cohort are presented through 12 months.