Cardiology and Angiology, University Medical Center Freiburg, Germany.
Hamostaseologie. 2012;32(3):221-7. doi: 10.5482/HAMO-12-05-0006. Epub 2012 Jul 10.
Vorapaxar is the first substance of a new class of antiplatelet drugs that has been tested in large clinical trials. The protease-activated receptor 1 (PAR-1) antagonist inhibits thrombin-induced platelet activation to prevent atherothrombosis. In the phase 3 trials TRACER (acute coronary syndrome) and TRA 2P-TIMI 50 (stable atherosclerosis) reducing ischemic events with vorapaxar came at the cost of bleeding. TRACER compared vorapaxar to placebo in 12,944 patients who had non-ST-segment elevation acute coronary syndromes on top of contemporary treatment including dual antiplatelet therapy (aspirin and clopidogrel). Vorapaxar reduced ischemic events non-significantly, but increased bleeding significantly, therefore not justifying triple antiplatelet therapy in this setting. Follow-up was stopped early because of bleeding. TRA 2P-TIMI 50 examined 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease. Vorapaxar reduced ischemic events and increased bleeding both significantly. Recruitment of patients with prior stroke was stopped early. Net clinical outcome and subgroup analyses suggested that vorapaxar could be beneficial for patients with prior myocardial infarction - but no history of stroke.
沃拉帕沙是新型抗血小板药物中的第一种，已在大型临床试验中进行了测试。蛋白酶激活受体 1（PAR-1）拮抗剂可抑制凝血酶诱导的血小板激活，从而预防动脉粥样血栓形成。在 TRACER（急性冠状动脉综合征）和 TRA 2P-TIMI 50（稳定的动脉粥样硬化）这两项 3 期临床试验中，沃拉帕沙减少缺血事件的发生是以出血增加为代价的。TRACER 将沃拉帕沙与安慰剂在 12944 名接受非 ST 段抬高型急性冠状动脉综合征治疗的患者中进行了比较，这些患者在接受当代治疗的基础上（包括双联抗血小板治疗[阿司匹林和氯吡格雷]）。沃拉帕沙并未显著减少缺血事件，但显著增加了出血，因此在这种情况下并不支持三联抗血小板治疗。由于出血，随访提前停止。TRA 2P-TIMI 50 研究了 26449 名有心肌梗死、缺血性卒中和外周动脉疾病病史的患者。沃拉帕沙减少了缺血事件和出血事件，且均具有显著意义。先前有卒中史的患者招募提前停止。净临床结局和亚组分析表明，沃拉帕沙可能对有心肌梗死病史但无卒中史的患者有益。
