BACKGROUND:In the ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial, the prasugrel pre-treatment strategy versus placebo was associated with excess bleeding complications and no improved ischemic outcome in non-ST-segment elevation myocardial infarction (MI). Whether patients with the longest pre-treatment duration had an ischemic benefit is unknown.OBJECTIVES:This pre-specified analysis of the ACCOAST trial aimed to assess the effect of pre-treatment duration with prasugrel (time from randomization to angiography) on outcomes.METHODS:Within the 4,033 patients randomized in the ACCOAST trial, pre-treatment duration was available in 4,001 patients (99.2%). The population of the trial was divided into quartiles of pre-treatment duration (0.1 to 2.5 h, 2.5 to 3.9 h, 3.9 to 13.6 h, and >13.6 h) with an evaluation of the primary efficacy endpoint of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use. Secondary efficacy outcomes including cardiovascular death, MI, or stroke; all-cause death; stent thrombosis and safety outcomes (all coronary artery bypass graft [CABG] or non-CABG TIMI [Thrombolysis In Myocardial Infarction] major bleeding) were also evaluated at 7 days.RESULTS:The primary efficacy outcome of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use did not differ between the quartiles of pre-treatment duration in the trial population (p = 0.17 for interaction). None of the secondary efficacy outcomes were found to be dependent on pre-treatment duration. The safety outcome of all CABG or non-CABG TIMI major bleeding did not differ between the quartiles of pre-treatment duration (p = 0.37 for interaction).CONCLUSIONS:In non-ST-segment elevation MI patients, the excess risk of bleeding and the absence of ischemic benefit were consistent across the quartiles of increasing duration of prasugrel pre-treatment. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287).