PAR-1 antagonists: current state of evidence.
Vorapaxar (SCH 530348) and atopaxar (E5555) are oral protease-activated receptor-1 (PAR-1) antagonists with high bioavailability. They inhibits thrombin induced platelet aggregation by competitively inhibiting PAR-1. We systematically evaluated the evidence for the efficacy and safety of all PAR-1 antagonists as well as for the individual drugs vorapaxar and atopaxar in different databases-PubMed, EMBASE, Scopus, and Cochrane register of Controlled Clinical Trials (CENTRAL).We selected randomized controlled trials of PAR-1 antagonists that reported on cardiovascular mortality as a clinical outcome. The random-effects Mantel-Haenszel model was used to evaluate the effect of PAR-1 antagonists on cardiovascular mortality. Seven trials were selected (N = 42,355) for analysis. PAR-1 antagonists as a class, as well as individually, were associated with a non-significant numerically lower risk of cardiovascular mortality than that seen with agents used in the control group; RR, 0.93; 95% CI, 0.83-1.04; P = 0.20). No heterogeneity was noted. However, PAR-1 antagonists also appeared to increase the risk of bleeding significantly. PAR-1 antagonists appear to be associated with some reduction in the risk of cardiovascular mortality; however the significantly higher bleeding risk noted with PAR-1 antagonists appear to mandate a very careful selection of patients that may benefit without a substantially increased risk of bleeds.
Maimonides Medical Center, 864 49th Street Apt C11, Brooklyn, NY 11220, USA. sauravchatterjeemd@gmail.com
Saurav
S
Chatterjee
Abhishek
A
Sharma
Debabrata
D
Mukherjee
D003324:Coronary Artery Disease / Q000188:drug therapy / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D007097:Imines / Q000009:adverse effects / Q000627:therapeutic use; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D039781:PubMed; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
C540445:E 5555; D007097:Imines; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar