糖尿病合并既往心肌梗死患者使用vorapaxar：来自凝血酶受体拮抗剂在动脉粥样硬化血栓形成性缺血事件二级预防中的研究——TIMI 50试验的结果
Vorapaxar in patients with diabetes mellitus and previous myocardial infarction: findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial.
作者信息
Cavender Matthew A, Scirica Benjamin M, Bonaca Marc P, Angiolillo Dominick J, Dalby Anthony J, Dellborg Mikael, Morais Joao, Murphy Sabina A, Ophuis Ton Oude, Tendera Michal, Braunwald Eugene, Morrow David A
机构信息
From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
出版信息
Circulation. 2015 Mar 24;131(12):1047-53. doi: 10.1161/CIRCULATIONAHA.114.013774. Epub 2015 Feb 13.
BACKGROUND
Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.
METHODS AND RESULTS
We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60-0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07-2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67-0.93]).
CONCLUSIONS
In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.
背景
沃拉帕沙可降低既往心肌梗死（MI）患者的心血管死亡、心肌梗死或卒中风险，但会增加出血风险。尽管接受了标准治疗，糖尿病（DM）患者仍有较高的复发性血栓形成事件风险，可能从抗栓治疗中特别获益。凝血酶受体拮抗剂在动脉粥样硬化性缺血事件二级预防中的应用——TIMI 50试验是一项针对稳定型动脉粥样硬化患者的沃拉帕沙随机、双盲、安慰剂对照试验。
方法与结果
我们研究了沃拉帕沙在既往有心肌梗死且符合试验条件的糖尿病患者和非糖尿病患者中的疗效。由于有卒中或短暂性脑缺血发作病史的患者禁用沃拉帕沙，因此分析（n = 16896）排除了此类患者。糖尿病患者发生心血管死亡、心肌梗死或卒中的主要终点事件比非糖尿病患者更频繁（安慰剂组发生率：14.3%对7.6%；调整后风险比，1.47；P<0.001）。在糖尿病患者（n = 3623）中，沃拉帕沙显著降低了主要终点事件（11.4%对14.3%；风险比，0.73[95%置信区间，0.60 - 0.89]；P = 0.002），避免1次主要心血管事件所需治疗人数为29。糖尿病患者使用沃拉帕沙后中度/重度出血发生率增加（4.4%对2.6%；风险比，1.60[95%置信区间，1.07 - 2.40]）。然而，综合这两个终点（疗效和安全性）的净临床结局因沃拉帕沙而得到改善（风险比，0.79[95%置信区间，0.67 - 0.93]）。
结论
在既往有心肌梗死和糖尿病的患者中，在标准治疗基础上加用沃拉帕沙可显著降低主要血管事件风险，在这类复发性缺血事件高风险人群中具有更大的绝对获益潜力。
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