Department of Cardiology and Angiology, Eberhard Karls University Tübingen, Tübingen, Germany.
Institute for Clinical Epidemiology and Applied Biometry, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.
NEJM Evid. 2024 Jan;3(1):EVIDoa2300235. doi: 10.1056/EVIDoa2300235. Epub 2023 Dec 22.
Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)
在栓塞性卒中和来源不明（ESUS）的患者中，利伐沙班和达比加群并不优于阿司匹林。阿哌沙班是否优于 ESUS 患者和已知心源性栓塞危险因素的阿司匹林，尚不清楚。
我们进行了一项多中心、随机、开放标签、盲终点试验，比较了阿哌沙班（5mg，每日 2 次）与阿司匹林（100mg，每日 1 次），起始于 ESUS 后 28 天内至少有一个预测因素为房颤或卵圆孔未闭的患者。强制性进行心脏监测，如果发现房颤，则将阿司匹林治疗转换为阿哌沙班。主要结局是在 12 个月随访期间脑磁共振成像（MRI）上出现任何新的缺血性病变。次要结局包括主要和临床相关的非主要出血。
共有 352 名患者随机分配接受阿哌沙班（178 名患者）或阿司匹林（174 名患者），中位数为 ESUS 后 8 天。在 12 个月的随访中，325 名参与者（92.3%）可进行 MRI 随访。阿哌沙班组 169 名参与者中有 23 名（13.6%）和阿司匹林组 156 名参与者中有 25 名（16.0%）发生新的缺血性病变（调整后的优势比，0.79；95%置信区间，0.42 至 1.48；P=0.57）。5 名和 7 名参与者分别发生主要和临床相关的非主要出血（1 年累积发生率，2.9%和 4.2%；风险比，0.68；95%置信区间，0.22 至 2.16）。接受阿哌沙班治疗的患者每 100 人年发生 43.9 例严重不良事件，接受阿司匹林治疗的患者每 100 人年发生 45.7 例。由于无效，阿哌沙班治疗栓塞性卒中和来源不明的试验在预先指定的中期分析后终止。
在 ESUS 人群中，阿哌沙班治疗并不优于心脏监测指导下的阿司匹林，不能预防新的缺血性病变。（由 Bristol-Myers Squibb 和 Medtronic Europe 资助；ClinicalTrials.gov 编号，NCT02427126）
