Optimal- vs. standard-antiplatelet therapy on platelet function and long-term clinical outcomes in patients with high on-treatment platelet reactivity: 2-year outcomes of the multicentre, randomized Optimal-antiPlatelet Therapy (OPT) trial

Abstract

Optimal strategy for the management of high on-treatment platelet reactivity (HPR), an independent predictor of ischaemic events, is not yet clear. The aim of this study was to explore the safety and efficacy of personalized antiplatelet therapy based on platelet function testing in patients with HPR. A total of 840 patients with HPR who underwent coronary stenting for acute coronary syndrome (ACS) were randomly assigned in a 1:2 ratio to receive standard dual-antiplatelet therapy ( n = 280) or platelet function-guided optimal-antiplatelet therapy ( n = 560). In the optimal group, patients initially received clopidogrel 150 mg/day on top of aspirin and switched to triple antiplatelet therapy with additional cilostazol if repeat platelet function assay after 3 days indicated a sustained HPR. The primary endpoint was the composite of all-cause death, myocardial infarction, clinically driven target vessel revascularization (TVR), or stroke. Optimal therapy resulted in significantly lower 30-day HPR rate (30.1 vs. 44.3%, P < 0.001). At 1-year follow up, optimal therapy was associated with significantly lower incidence of primary endpoint events (2.7 vs. 6.8%, P = 0.006) compared with standard therapy, mainly due to the reduction of TVR. These beneficial effects were sustained at 2 years (4.5 vs. 9.2%, P = 0.006), with similar bleeding event rates between groups (7.3 vs. 6.5%, P = 0.565). Optimal-antiplatelet therapy based on platelet function testing is effective in attenuating HPR and improving long-term outcomes for ACS patients with no increase in bleeding events.