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

Int J Cardiol. 2017 Jan 15;227:617-624. doi: 10.1016/j.ijcard.2016.10.088. Epub 2016 Oct 29.

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.

Keywords: Atherosclerotic vascular disease; Vorapaxar.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Atherosclerosis / diagnosis
  • Atherosclerosis / epidemiology
  • Atherosclerosis / prevention & control*
  • Clinical Trials, Phase III as Topic / methods
  • Humans
  • Lactones / administration & dosage*
  • Multicenter Studies as Topic / methods
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Pyridines / administration & dosage*
  • Randomized Controlled Trials as Topic* / methods
  • Secondary Prevention / methods*
  • Treatment Outcome

Substances

  • Lactones
  • Platelet Aggregation Inhibitors
  • Pyridines
  • vorapaxar