From TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., M.P.B., S.A.M., B.M.S., E.B., D.A.M.); Department of Cardiovascular Medicine, Flinders Cardiovascular Center, Adelaide, Australia (P.E.A.); Cardiovascular Division, Pontificia Universidad Catolica de Chile, Santiago, Chile (R.L.C.); Department of Cardiology, Military Hospital, Budapest, Hungary (R.G.K.); and Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand (H.W.).
Circulation. 2015 Nov 17;132(20):1871-9. doi: 10.1161/CIRCULATIONAHA.114.015042. Epub 2015 Sep 3.
Vorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use.
The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with previous atherothrombosis. This prespecified analysis included 16,897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI, and stroke in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, P<0.001; no planned thienopyridine, hazard ratio, 0.75; 0.60-0.94, P=0.011; P-interaction=0.67). Findings were similar when patients were stratified by actual thienopyridine use at baseline (P-interaction=0.82) and through 18 months (P-interaction=0.44). Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, P<0.001; no planned, hazard ratio, 1.90, 1.17-3.07, P=0.009; P-interaction=0.37) or actual thienopyridine use (P-interaction=0.24).
Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of previous MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.
Vorapaxar 拮抗蛋白酶激活受体 1，即人类血小板上凝血酶的主要受体，可减少先前发生心肌梗死（MI）的稳定患者中复发性血栓事件。我们希望确定 Vorapaxar 的抗血小板治疗效果和安全性是否会因同时使用噻吩吡啶类药物而改变。
血栓素受体拮抗剂在动脉粥样硬化血栓缺血性事件的二级预防-心肌梗死溶栓 50 （TRA 2°P-TIMI 50）是一项随机、双盲、安慰剂对照的 Vorapaxar 试验，纳入了 26449 例先前有动脉粥样硬化血栓形成的患者。本预先设定的分析包括 16897 例在前 2 周到 12 个月内发生 MI 的患者，并且由于在该人群中存在禁忌证，因此仅限于没有中风或短暂性脑缺血发作病史的患者。随机化基于计划使用噻吩吡啶类药物进行分层。在 12410 例（73%）患者中随机进行噻吩吡啶类药物计划治疗。与安慰剂相比，无论是否计划使用噻吩吡啶类药物，Vorapaxar 均显著降低心血管死亡、MI 和卒中的复合终点（计划使用噻吩吡啶类药物时，风险比为 0.80，0.70-0.91，P<0.001；未计划使用噻吩吡啶类药物时，风险比为 0.75；0.60-0.94，P=0.011；P 交互作用=0.67）。当根据基线（P 交互作用=0.82）和 18 个月（P 交互作用=0.44）时的实际噻吩吡啶类药物使用情况对患者进行分层时，发现结果相似。全球使用策略开通闭塞冠状动脉（GUSTO）中度或重度出血风险增加与 Vorapaxar 相关，并且未因计划使用噻吩吡啶类药物（计划时，风险比为 1.50；1.18-1.89，P<0.001；未计划时，风险比为 1.90，1.17-3.07，P=0.009；P 交互作用=0.37）或实际噻吩吡啶类药物使用（P 交互作用=0.24）而显著改变。
Vorapaxar 降低了有先前 MI 病史的稳定患者的心血管死亡、MI 或卒中，无论是否同时使用噻吩吡啶类药物。不论噻吩吡啶类药物的使用情况如何，中度或重度出血的相对风险均相似增加。
