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Safety and Efficacy of PAR-1 Antagonists in Patients with Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials.
MedLine Citation:
PMID:  22845871     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Thrombin receptor antagonists blocking the protease-activated-receptor-1 (PAR-1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations. Objectives: We investigated the safety and efficacy of PAR-1 antagonists in patients with coronary artery disease (CAD). Patients/Methods: Randomized, placebo-controlled trials of PAR-1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death/myocardial infarction (MI)/stroke. Results: A total of 41,647 patients from eight trials were included. PAR-1 antagonists were associated with higher risk of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39-1.57, P<0.001), major (1.46, 95% CI 1.28-1.67, P<0.001) and minor (1.67, 95% CI 1.40-2.00, P<0.001) bleeding compared with placebo in the fixed-effects model. PAR-1 antagonists reduced the composite of death/MI/stroke compared with placebo (OR 0.87, 95% CI 0.81-0.92, P<0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.78-0.92, P<0.001). Conversely, PAR-1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.90-1.09, P=0.81) or stroke (OR 0.96, 95% CI 0.84-1.10, P=0.59). Conclusions: PAR-1 antagonists decrease ischemic events in patients with CAD compared with placebo, mainly driven by a reduction in MI, at the cost of an increased hazard for clinically significant bleeding. © 2012 International Society on Thrombosis and Haemostasis.
Authors:
D Capodanno; D L Bhatt; S Goto; M L O'Donoghue; D J Moliterno; C Tamburino; D J Angiolillo
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Affiliation:
Ferrarotto Hospital, Catania, Italy ETNA Foundation, Catania, Italy University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA VA Boston Healthcare System TIMI Study Group, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA Division of Cardiology, Tokai University School of Medicine, Kanagawa, Japan University of Kentucky, Lexington, KY, USA.
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