Abstract 19049: Net Clinical Benefit of Vorapaxar in NSTE ACS: Role of Ischemic and Bleeding Risk Stratification

Abstract

Background: In 12,944 NSTE ACS pts included in the TRACER trial, platelet protease-activated-receptor 1 (PAR-1) antagonist vorapaxar, on top of standard of care with high thienopyridine use, was associated with an 11% reduction in CV death, MI, or stroke and an increased risk of bleeding. The trial was broadly inclusive and did not exclude pts based on bleeding risk. We evaluated the net clinical benefit of vorapaxar in the randomized population and according to patients’ predicted risks of ischemic events and major bleeding. Methods: Using multivariable models developed in the TRACER placebo group to predict 1-yr major bleeding (GUSTO severe or TIMI major bleeding) and recurrent ischemic events (composite of CV death, MI, stroke), patients were stratified into 2 bleeding risk categories (predicted rate >5% vs ≤5%) and 2 ischemic risk categories (predicted rate >13% vs ≤13%). Net clinical outcome was measured as the difference in treatment effects on the composite ischemic endpoint vs bleeding outcome. Results: Overall at 1-yr, vorapaxar resulted in a 1.30% absolute reduction in CV death, MI, and stroke and a 0.94% absolute increase in GUSTO severe bleeding (net benefit +0.34%). In pts with an increased risk of bleeding, vorapaxar had negative net clinical benefit (Figure). Among pts with high risk of ischemic events but low risk of bleeding (26% of the population), vorapaxar produced a favorable 2.8% absolute net benefit. Conclusion: Vorapaxar was associated with an improved net benefit in a selected but large group of NSTE ACS patients with high risk of recurrent ischemic events and low risk of bleeding, identified through the application of multivariable risk stratification strategies. Appropriate selection of patients in NSTE ACS, with the risk of bleeding balanced against that of recurrent ischemic events, appears to be a determinant of improved outcome with vorapaxar added to standard of care and high use of dual antiplatelet therapy.