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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews.

PAR-1 antagonists: current state of evidence

Review published: 2013.

Bibliographic details: Chatterjee S, Sharma A, Mukherjee D.  PAR-1 antagonists: current state of evidence. Journal of Thrombosis and Thrombolysis 2013; 35(1): 1-9. [PubMed: 22644721]


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.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

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