Continued vorapaxar versus withdrawed clopidogrel both on top of low dose aspirin in patients undergoing heart surgery: A call for randomized trial

Abstract

Despite advanced techniques and improved clinical outcomes, the optimal antiplatelet strategy following coronary artery bypass grafting (CABG) is an unsolved mystery. Vorapaxar, a novel platelet thrombin receptor (PAR-1/4) blocker, is currently approved for post-myocardial infarction and peripheral artery disease indications on top of clopidogrel or/and aspirin. We here summarize the outcomes in patients after CABG for justification of a future vorapaxar trial. We comprehended the CABG outcomes after vorapaxar yielded from TRACER, TRA2P trials, and affiliated FDA reviews. The verified evidence suggests that composite of death, myocardial infarction and stroke occurred in 2.2% of vorapaxar vs. 8.1% placebo in TRA2P. These data were similar to the endpoint differences (5.9% after vorapaxar vs. 8.3% for placebo) in TRACER. The mortality reduction also consistently suggests vorapaxar advantage (1.7% vs. 2.5% in TRA2P, and 1.7% vs. 3.9% in TRACER). Notably, the post-CABG bleeding risks after vorapaxar were only slightly, but not significantly higher. Moreover, the bleeding disadvantage in the experimental arm was most likely related to overtreatment since majority of patients in both TRACER and TRA2P received triple antiplatelet therapy with aspirin, clopidogrel on top of vorapaxar. Overall, the FDA-confirmed evidence advocate for the future vorapaxar post-CABG outcome-driven trial. The head-to-head trial testing dual therapy with continued over CABG vorapaxar versus withdrawed clopidogrel, both on top of low dose aspirin is warranted. We conclude that the primary outcomes including mortality were consistently better for heart surgery patients after vorapaxar, while the excess of bleeding was mild. Continuing vorapaxar during CABG may be superior to currently recommended withdrawal antiplatelet strategies, and should be tested in an adequately powered randomized outcome-driven trial.

Keywords: Bleeding; Clinical outcomes; Clinical trials; Efficacy; Heart surgery; Mortality; Vorapaxar.