Abstract 13846: The Relationship of Platelet Function Measurements with Bleeding Outcomes During Long-term Treatment with Dual Antiplatelet Therapy in Medically Managed NSTE-ACS Patients

Abstract

Introduction: The relationship of low “on-treatment” platelet reactivity to longitudinal risks of major bleeding following acute coronary syndromes (ACS) has not been clearly delineated. Methods: We analyzed 2428 patients with non-ST-elevation ACS (NSTE ACS) from the TRILOGY ACS trial who were managed without revascularization and had platelet reactivity measurements (P2Y12 reaction units [PRUs]) collected in a platelet function substudy. Patients received aspirin + prasugrel (10 mg/d; 5 mg/d for those ≥75 y or <75 y and <60 kg) or clopidogrel (75 mg/d). Non-CABG severe/moderate GUSTO bleeding and non-CABG TIMI major/minor bleeding were ascertained through 30 months. Contal’s method was used to investigate whether a PRU cut point could distinguish high vs low bleeding risk. Multivariable Cox proportional hazard models were used to evaluate the association between PRU and time to first bleed. Results: Through 30 months, there were 27 GUSTO severe/moderate bleeds and 37 TIMI major/minor bleeds, with gastrointestinal bleeding the most common. Baseline characteristics were stratified by tertiles of PRU values at 5 d, and significant differences were seen across tertiles (Table). Unadjusted bleeding rates appeared highest among those in the lowest PRU tertile but no reliable PRU cut point was found that significantly distinguished bleeding risk. Unadjusted analyses showed continuous measures of PRUs were not associated with GUSTO (HR=1.00, 95% CI: 0.96-1.04) or TIMI bleeding (HR=1.03, 95% CI: 0.99-1.06). This relationship did not change after multivariable adjustment. Conclusions: Among NSTE-ACS patients managed without revascularization and receiving dual antiplatelet therapy, PRU values were not significantly associated with long-term bleeding risk. The relatively small number of bleeding events accrued limited study power, but these results suggest that low “on-treatment” platelet reactivity does not independently predict post-ACS bleeding risk.