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Safety and efficacy of protease-activated receptor-1 antagonists in patients with coronary artery disease: a meta-analysis of randomized clinical trials.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2012 Oct; Vol. 10 (10), pp. 2006-15. - Publication Year :
- 2012
-
Abstract
- Background: Thrombin receptor antagonists blocking protease-activated receptor-1 (PAR-1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations.<br />Objectives: We investigated the safety and efficacy of PAR-1 antagonists in patients with coronary artery disease (CAD).<br />Patients/methods: Randomized, placebo-controlled trials of the 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) or stroke.<br />Results: A total of 41 647 patients from eight trials were included. PAR-1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39-1.57, P < 0.001), major (OR 1.46, 95% CI 1.28-1.67, P < 0.001) and minor (OR 1.67, 95% CI 1.40-2.00, P < 0.001) bleeding than placebo in the fixed-effects model. PAR-1 antagonists reduced the composite of death, MI or stroke as 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).<br />Conclusions: PAR-1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding.<br /> (© 2012 International Society on Thrombosis and Haemostasis.)
- Subjects :
- Blood Platelets metabolism
Chi-Square Distribution
Coronary Artery Disease blood
Coronary Artery Disease complications
Coronary Artery Disease mortality
Evidence-Based Medicine
Hemorrhage chemically induced
Humans
Imines adverse effects
Lactones adverse effects
Myocardial Infarction etiology
Myocardial Infarction prevention & control
Odds Ratio
Platelet Aggregation Inhibitors adverse effects
Pyridines adverse effects
Randomized Controlled Trials as Topic
Receptor, PAR-1 blood
Risk Assessment
Risk Factors
Stroke etiology
Stroke prevention & control
Treatment Outcome
Blood Platelets drug effects
Coronary Artery Disease drug therapy
Imines therapeutic use
Lactones therapeutic use
Platelet Aggregation Inhibitors therapeutic use
Pyridines therapeutic use
Receptor, PAR-1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7836
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 22845871
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2012.04869.x