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.


CONCLUSIONS
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.
Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, New York, NY, United States; Institute of Cardiovascular Research and Technology, Brooklyn, NY, United States. Electronic address: abhisheksharma4mamc@gmail.com.
Abhishek
A
Sharma
Institut de Cardiologie, Hôpital Pitié-Salpétrière, Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie, Boulevard de l'Hôpital, Paris, France; Institute of Cardiometabolism and Nutrition, Hôpital Pitié-Salpétrière, Paris, France.
Gérard
G
Helft
Department of Medicine, James J. Peters VA Medical Center, Mount Sinai School of Medicine, New York, NY, United States.
Aakash
A
Garg
Division of Cardiology, St. Luke's University Health Network, Bethlehem, PA, United States.
Sahil
S
Agrawal
Division of Cardiovascular Diseases, St. Luke's-Roosevelt Hospital Center of the Mount Sinai Health System, New York, NY, United States.
Saurav
S
Chatterjee
Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, United States.
Carl J
CJ
Lavie
Department of Cardiology, Maimonides Medical Center, New York, NY, United States.
Sunny
S
Goel
Division of Cardiology, Texas Tech University, El Paso, TX, United States.
Debabrata
D
Mukherjee
Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, New York, NY, United States.
Jonathan D
JD
Marmur
D050197:Atherosclerosis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D006801:Humans; D007783:Lactones / Q000008:administration & dosage*; D015337:Multicenter Studies as Topic / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D055502:Secondary Prevention / Q000379:methods*; D016896:Treatment Outcome
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
Atherosclerotic vascular disease; Vorapaxar