Sharma, Abhishek; Helft, Gerard; Garg, Aakash; Agrawal, Sahil; Chatterjee, Saurav; Lavie, Carl J.; Goel, Sunny; Mukherjee, Debabrata; Marmur, Jonathan D.
Abstract
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
