Background and Purpose:Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source.Methods:Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily.Results:During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7–4.3]), East Asia region (HR, 2.5 [95% CI, 1.6–3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2–3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m² decrease, [95% CI, 1.0–1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2–18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin.Conclusions:Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk.Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

中文翻译：

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未确定的栓塞性卒中患者的主要出血频率和预测因素资料来源：NAVIGATE-ESUS试验。

背景和目的：对于尚未确定来源的近期栓塞性卒中患者，抗栓治疗期间主要出血的风险，部位和预测因素尚未明确。方法：对国际血栓形成和止血标准中定义的主要出血的探索性研究进行了分析，涉及7213人不确定来源的随机试验的国际NAVIGATE（全球试验新方法利伐沙班抑制因子Xa的栓塞性卒中）的参与者进行比较，比较了利伐沙班每天15 mg与阿司匹林每天100 mg的结果。结果：在11个月的中位随访中，有85次重大出血发生。最常见的部位是胃肠道（38％），其次是颅内（29％）。分配给利伐沙班（危险比[HR]，2.7 [95％CI，1.7-4.3]），东亚地区（HR，2.5 [95％CI，1.6-3.9]），²下降[95％CI，1.0–1.3]）与主要出血的存在独立相关。五人（6％）是致命的。在15例脑出血患者中，有2例（13％）死亡。没有证据表明利伐沙班开始后有早期高危期。东亚参与者的脑出血的年化率（0.67％）是所有其他地区（0.11％； HR，6.3 [95％CI，2.2-18.0]）的六倍。结论：利伐沙班和阿司匹林的出血部位相似。结论：参加国际随机试验的未确定来源患者的栓塞性卒中中，主要出血的独立预测因素被分配给利伐沙班，东亚地区，收缩压升高和肾功能受损。 。东亚地区与脑出血的风险密切相关。估计肾小球滤过率应作为分层出血风险的考虑因素。注册：URL：https://www.clinicaltrials.gov。唯一标识符：NCT02313909。