Safety and efficacy of vorapaxar in secondary prevention of atherosclerotic disease: A meta-analysis of randomized control trials

Objective To study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. Methods A systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction (MI), ischemic stroke and repeat revascularization. The pre-specified safety endpoint was intracranial hemorrhage (ICH) and a composite of TIMI major and minor bleeding. Risk ratios were used as the metric of choice by applying random effects models. Results Five randomized controlled trials with 40,630 patients were included in final analysis. Compared with placebo, vorapaxar led to a statistically non-significant reduction in risk of MI [RR 0.86; 95% CI 0.80–0.93, p = 0.427] and ischemic stroke [RR 0.84; 95% CI 0.72–0.97, p = 0.920]. No differences were observed between vorapaxar and placebo with respect to all-cause mortality [RR 0.99; 95% CI 0.90–1.08, p = 0.620], cardiovascular mortality [RR 0.94; 95% CI 0.83–1.06, p = 0.351], repeat revascularization [RR 0.97; 95% CI 0.82–1.15, p = 0.236], and TIMI bleeding [RR 1.29; 95% CI 0.98–1.69, p = 0.126]. Vorapaxar was associated with a statistically non-significant higher risk of ICH [RR 2.36; 95% CI 1.40–3.96, p = 0.137] compared with placebo. Conclusion Addition of Vorapaxar to standard medical therapy in in patients with atherosclerotic disease led to a statistically non-significant reduction in the risk of MI and ischemic stroke at the cost of statistically non-significant increase in risk of ICH.