National Cerebral and Cardiovascular Center.
International University of Health and Welfare, Sanno Hospital and Sanno Medical Center.
Circ J. 2020 Nov 25;84(12):2286-2295. doi: 10.1253/circj.CJ-20-0563. Epub 2020 Oct 30.
The international 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 (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.
ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09).
Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.
国际随机、双盲、二次卒中预防评估试验比较了口服凝血酶抑制剂达比加群酯与阿司匹林在不明来源栓塞性卒中（ESUS）患者中的疗效和安全性（RE-SPECT ESUS）试验未显示达比加群酯优于阿司匹林降低不明来源栓塞性卒中（ESUS）患者的复发性卒中。基于预先定义的亚分析，评估了达比加群酯与阿司匹林在日本患者中的安全性和疗效。
ESUS 患者随机接受达比加群酯（150 或 110mg，每日两次）或阿司匹林（100mg，每日一次）治疗。在 5390 名随机患者中，有 594 名是日本人。大多数日本患者（99.8%）接受了试验筛查的脑部磁共振成像，而非日本患者为 76.8%（P<0.0001）。在日本队列中，在 19.4 个月的中位随访期间，达比加群酯组 294 例中有 20 例（4.3%/年）发生主要终点复发性卒中，阿司匹林组 300 例中有 38 例（8.3%/年）（风险比[HR]，0.55；95%置信区间[CI]，0.32-0.94）。大出血分别发生在 12 例（2.5%/年）和 17 例（3.5%/年）患者中（HR，0.72；95% CI，0.34-1.52）。相比之下，在非日本队列中，达比加群酯组和阿司匹林组的复发性卒中发生率分别为 4.1%/年和 4.3%/年，达比加群酯与阿司匹林相比，复发性卒中无明显差异（HR，0.91；95% CI，0.74-1.14）。治疗和地区的 P 交互作用未达到统计学意义（P=0.09）。
在日本 ESUS 患者中，与阿司匹林相比，达比加群酯可能与较低的复发性卒中相对风险相关。
