Wang Amy
a Arnold and Marie Schwartz College of Pharmacy and Health Sciences , Long Island University , Brooklyn , NY , USA.
Expert Opin Pharmacother. 2015;16(16):2509-22. doi: 10.1517/14656566.2015.1099629. Epub 2015 Oct 19.
Atherosclerosis is frequently caused by clot blockage of the coronary or peripheral arteries, and may lead to myocardial infarction (MI) or peripheral arterial disease (PAD). Despite advancements in management of atherosclerosis, mortality and ischemic rates remain high. Vorapaxar is a protease activated receptor-1 (PAR-1) antagonist, and prevents thrombin activation of PAR-1 receptors on platelets.
Vorapaxar was studied in 2 landmark trials in patients with acute coronary syndrome (ACS) and in those with history of atherosclerosis. For patients with ACS, vorapaxar did not significantly reduce rates of the primary efficacy outcome as compared to placebo. For patients with a history of atherosclerosis, vorapaxar significantly reduced rates of primacy outcome. However, in both landmark trials, vorapaxar significantly increased risks of bleeding, and significantly increases risks of intracranial hemorrhage in patients with a history of stroke. Vorapaxar was approved in 2014 in the US for patients with a history of MI or PAD, and in the European Union for patients with a history of MI.
Use of vorapaxar may be limited due to its high potential for causing bleeding. Efficacy of vorapaxar in addition to aspirin and prasugrel or ticagrelor for the management of ACS should be studied in the future.
动脉粥样硬化常由冠状动脉或外周动脉的血栓阻塞引起,可能导致心肌梗死(MI)或外周动脉疾病(PAD)。尽管在动脉粥样硬化的管理方面取得了进展,但死亡率和缺血率仍然很高。沃拉帕沙是一种蛋白酶激活受体-1(PAR-1)拮抗剂,可防止凝血酶激活血小板上的PAR-1受体。
在两项具有里程碑意义的试验中对沃拉帕沙进行了研究,一项针对急性冠状动脉综合征(ACS)患者,另一项针对有动脉粥样硬化病史的患者。对于ACS患者,与安慰剂相比,沃拉帕沙并未显著降低主要疗效结局的发生率。对于有动脉粥样硬化病史的患者,沃拉帕沙显著降低了主要结局的发生率。然而,在这两项具有里程碑意义的试验中,沃拉帕沙均显著增加了出血风险,并且在有中风病史的患者中显著增加了颅内出血风险。2014年,沃拉帕沙在美国被批准用于有MI或PAD病史的患者,在欧盟被批准用于有MI病史的患者。
由于沃拉帕沙有很高的出血风险,其使用可能受到限制。未来应研究沃拉帕沙联合阿司匹林和普拉格雷或替格瑞洛用于ACS管理的疗效。