期刊
CIRCULATION
卷 127, 期 14, 页码 1522-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.112.000679
关键词
ischemia; outcome assessment; peripheral arterial disease; platelet aggregation inhibitors; vorapaxar
资金
- Merck and Co.
- Accumetrics
- Amgen
- AstraZeneca
- Beckman Coulter
- Bristol-Myers Squibb
- CV Therapeutics
- Daiichi Sankyo Co Ltd
- Eli Lilly and Co
- GlaxoSmithKline
- Integrated Therapeutics
- Nanosphere
- Novartis Pharmaceuticals
- Nuvelo
- OrthoClinical Diagnostics
- Pfizer
- Roche Diagnostics
- Sanofi-Aventis
- Sanofi-Synthelabo
- Siemens Medical Solutions
- Singulex
- National Heart, Lung, and Blood Institute [K12 HL083786]
- Lexicon
- Arena
- Gilead
- Eisai
- Aastrom Biosciences
- Baxter Healthcare
- Genzyme
- Merck
- Plurestem
- Swiss National Foundation
- Bayer-Schering Pharma
- Schering-Plow
- Daiichi-Sankyo
- Boehringer-Ingelheim
- Actelion
- Eli Lilly
- Amarin Pharmaceuticals
- Beckman-Coulter
- Critical Diagnostics
- Genentech
- Instrumentation Laboratory
- Novartis
- Servier
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 degrees 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-Vorapaxar did not reduce the risk of cardiovascular death, myocardial infarction, or stroke in patients with peripheral artery disease; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of protease-activated receptor-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding.
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