Diener Hans-Christoph, Sacco Ralph L, Easton J Donald, Granger Christopher B, Bar Michal, Bernstein Richard A, Brainin Michael, Brueckmann Martina, Cronin Lisa, Donnan Geoffrey, Gdovinová Zuzana, Grauer Claudia, Kleine Eva, Kleinig Timothy J, Lyrer Philippe, Martins Sheila, Meyerhoff Juliane, Milling Truman, Pfeilschifter Waltraud, Poli Sven, Reif Michal, Rose David Z, Šaňák Daniel, Schäbitz Wolf-Rüdiger
From the Faculty of Medicine, Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Germany (H.-C.D.).
Clinical and Translational Science, Miller School of Medicine, University of Miami, FL (R.L.S.).
Stroke. 2020 Jun;51(6):1758-1765. doi: 10.1161/STROKEAHA.119.028643. Epub 2020 May 14.
Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
背景与目的——RE-SPECT ESUS试验（随机、双盲、不明来源栓塞性卒中患者二级预防中口服凝血酶抑制剂达比加群酯与阿司匹林疗效和安全性比较评估）检验了以下假设：在不明来源栓塞性卒中患者中，达比加群预防复发性卒中的效果优于阿司匹林。这项探索性亚组分析研究了年龄、肾功能（均为预先定义）和达比加群剂量（事后分析）对复发性卒中和大出血发生率的影响。方法——RE-SPECT ESUS是一项多中心、随机、双盲试验，比较达比加群150或110mg（年龄≥75岁和/或肌酐清除率30至<50ml/分钟的患者）每日两次与阿司匹林100mg每日一次的疗效。主要结局是复发性卒中。结果——该试验于2014年12月至2018年1月纳入5390例患者，在不明来源栓塞性卒中患者中，达比加群预防复发性卒中的效果未显示优于阿司匹林。然而，在符合较低达比加群剂量标准的人群中，达比加群组的复发性卒中发生率低于阿司匹林组（7.4%对13.0%；风险比，0.57[95%CI，0.39 - 0.82]；交互作用=0.01）。这主要由年龄≥75岁的亚组驱动（7.8%对12.4%；风险比，0.63[95%CI，0.43 - 0.94]；交互作用=0.10）。随着肾功能下降，达比加群组的卒中发生率往往低于阿司匹林组。无论肾功能如何，两种治疗的大出血风险相似，但老年患者中达比加群的出血率有低于阿司匹林的趋势。结论——在RE-SPECT ESUS的亚组分析中，对于符合较低剂量达比加群标准的患者，达比加群与阿司匹林相比降低了复发性卒中的发生率。这些结果有待进一步验证。阿司匹林仍然是不明来源栓塞性卒中患者的标准抗栓治疗药物。注册——网址：https://www.clinicaltrials.gov；唯一标识符：NCT02239120。
