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Efficacy and safety of vorapaxar as approved for clinical use in the United States.
- Source :
-
Journal of the American Heart Association [J Am Heart Assoc] 2015 Mar 19; Vol. 4 (3), pp. e001505. Date of Electronic Publication: 2015 Mar 19. - Publication Year :
- 2015
-
Abstract
- Background: Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).<br />Methods and Results: We examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 2°P-TIMI 50 trial. Of these, 16,897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70.<br />Conclusions: In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long-term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.<br />Clinical Trial Registration: URL: clinicaltrials.gov Unique Identifier: NCT00526474.<br /> (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Subjects :
- Aged
Double-Blind Method
Female
Hemorrhage chemically induced
Humans
Ischemic Attack, Transient mortality
Ischemic Attack, Transient prevention & control
Kaplan-Meier Estimate
Lactones adverse effects
Male
Middle Aged
Myocardial Infarction diagnosis
Myocardial Infarction metabolism
Myocardial Infarction mortality
Peripheral Arterial Disease diagnosis
Peripheral Arterial Disease metabolism
Peripheral Arterial Disease mortality
Platelet Aggregation Inhibitors adverse effects
Pyridines adverse effects
Receptor, PAR-1 metabolism
Recurrence
Risk Factors
Stroke mortality
Stroke prevention & control
Time Factors
Treatment Outcome
United States epidemiology
United States Food and Drug Administration
Drug Approval
Lactones therapeutic use
Myocardial Infarction drug therapy
Peripheral Arterial Disease drug therapy
Platelet Aggregation Inhibitors therapeutic use
Pyridines therapeutic use
Receptor, PAR-1 antagonists & inhibitors
Secondary Prevention methods
Subjects
Details
- Language :
- English
- ISSN :
- 2047-9980
- Volume :
- 4
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American Heart Association
- Publication Type :
- Academic Journal
- Accession number :
- 25792124
- Full Text :
- https://doi.org/10.1161/JAHA.114.001505