Abstract | BACKGROUND:
Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for peripheral revascularization. METHODS AND RESULTS: The Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with stable atherosclerotic vascular disease ( myocardial infarction, stroke, or peripheral artery disease). Patients with qualifying peripheral artery disease (n=3787) had a history of claudication and an ankle-brachial index of <0.85 or prior revascularization for limb ischemia. The primary efficacy end point was cardiovascular death, myocardial infarction, or stroke, and the principal safety end point was Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) bleeding. In the peripheral artery disease cohort, the primary end point did not differ significantly with vorapaxar (11.3% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.78-1.14; P=0.53). However, rates of hospitalization for acute limb ischemia (2.3% versus 3.9%; hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; P=0.006) and peripheral artery revascularization (18.4% versus 22.2%; hazard ratio, 0.84; 95% confidence interval, 0.73-0.97; P=0.017) were significantly lower in patients randomized to vorapaxar. Bleeding occurred more frequently with vorapaxar compared with placebo (7.4% versus 4.5%; hazard ratio, 1.62; 95% confidence interval, 1.21-2.18; P=0.001). CONCLUSIONS:
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Authors | Marc P Bonaca, Benjamin M Scirica, Mark A Creager, Jeffrey Olin, Henri Bounameaux, Mikael Dellborg, Jessica M Lamp, Sabina A Murphy, Eugene Braunwald, David A Morrow |
Journal | Circulation
(Circulation)
Vol. 127
Issue 14
Pg. 1522-9, 1529e1-6
(Apr 09 2013)
ISSN: 1524-4539 [Electronic] United States |
PMID | 23501976
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Lactones
- Pyridines
- Receptor, PAR-1
- Thrombin
- vorapaxar
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Topics |
- Aged
- Ankle Brachial Index
- Cohort Studies
- Comorbidity
- Double-Blind Method
- Extremities
(blood supply)
- Female
- Follow-Up Studies
- Hemorrhage
(chemically induced, mortality)
- Humans
- Ischemia
(drug therapy, mortality)
- Kaplan-Meier Estimate
- Lactones
(administration & dosage, adverse effects)
- Male
- Middle Aged
- Myocardial Infarction
(mortality)
- Peripheral Arterial Disease
(drug therapy, mortality)
- Pyridines
(administration & dosage, adverse effects)
- Receptor, PAR-1
(antagonists & inhibitors, metabolism)
- Risk Factors
- Stroke
(mortality)
- Thrombin
(metabolism)
- Treatment Outcome
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