房颤患者口服抗凝突破性卒中：竞争性病因与结局
ASPERA-R回顾性研究纳入1649例房颤口服抗凝期间发生突破性缺血性卒中的成人患者，24.3%存在竞争性病因（最常见为大动脉粥样硬化）。竞争性病因组90天复发性卒中风险更高（6.0% vs 2.7%；aHR 2.62，95%CI 2.01-3.42；p<0.001），残疾分布更差、全因死亡及中重度出血风险更高。
要点
- 房颤抗凝突破性卒中者约1/4存在竞争性病因，以大动脉粥样硬化为主。
- 竞争性病因与90天复发性卒中风险增加独立相关（aHR 2.62）。
- 竞争性病因组全因死亡和中重度出血风险亦升高，需个体化二级预防。
核心结论
- 房颤患者口服抗凝期间发生突破性缺血性卒中时，竞争性病因与90天复发性卒中、功能依赖、死亡及出血风险升高相关。
研究设计与样本
- ASPERA-R为回顾性多中心研究，纳入35个中心2020年2月至2025年2月收治的1649例成人房颤患者，均发生口服抗凝（末次摄入≤48小时）期间的突破性缺血性卒中。
主要发现
- 竞争性病因占24.3%，其中大动脉粥样硬化占59.9%。
- 加权人群中，竞争性病因组90天复发性卒中发生率为6.0%，无竞争性病因组为2.7%（aHR 2.62，95%CI 2.01-3.42；p<0.001）。
- 竞争性病因组残疾分布更差（aOR 1.30，95%CI 1.08-1.55；p=0.005），全因死亡风险更高（aHR 1.58，95%CI 1.18-2.12；p=0.002）。
- 竞争性病因组中重度出血风险更高（aHR 1.82，95%CI 1.08-3.09；p=0.026），但24小时出血转化更少（调整风险差-4.3%，95%CI -7.8%至-0.7%；p=0.020）。
临床怎么用
- 对房颤抗凝突破性卒中患者应评估竞争性病因，尤其大动脉粥样硬化，以指导个体化二级预防。
局限性
- 研究为回顾性观察设计，且关于治疗中抗凝质量的数据不完整。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) who experience an ischemic stroke despite oral anticoagulation (OAC) face a high risk of recurrence and bleeding. We aimed to compare 90-day outcomes between patients with and without competing stroke etiologies after a breakthrough ischemic stroke while on OAC for AF. METHODS: ASPERA-R retrospectively enrolled adults (>18 years) with AF who experienced a breakthrough ischemic stroke, defined as either first or recurrent event, occurring on continuous OAC (last intake ≤48 hours), across 35 centers from February 2020 to February 2025. Patients' eligibility required imaging-confirmed ischemic stroke, baseline vessel imaging, and a standardized 90-day follow-up. Patients with inadequate anticoagulant dosing or poor adherence were excluded. Competing etiologies were defined as any additional mechanism coexisting with cardioembolism and plausibly contributing to the index stroke. The primary outcome was 90-day recurrent ischemic stroke; secondary outcomes included modified Rankin Scale shift, myocardial infarction, and vascular and all-cause death. Bleedings were also evaluated. We performed inverse probability weighting to balance baseline covariates and applied Cox or regression models to compare outcomes. RESULTS: Among 1,649 patients (mean age 78 years, 47.8% male), 24.3% had competing etiologies, most commonly large artery atherosclerosis (59.9%). Considering the weighted population, 90-day recurrent ischemic stroke occurred more often in those with competing etiologies (6.0% vs 2.7%; adjusted hazard ratio [aHR] 2.62, 95% CI 2.01-3.42; p < 0.001). Risk was greatest for large artery atherosclerosis and other determined causes. Competing etiologies also had worse disability distribution (adjusted odds ratio 1.30, 95% CI 1.08-1.55; p = 0.005) and higher all-cause mortality (aHR 1.58, 95% CI 1.18-2.12; p = 0.002). Moderate-to-severe bleeding was higher with competing etiologies (aHR 1.82, 95% CI 1.08-3.09; p = 0.026), whereas 24-hour hemorrhagic transformation was less frequent (adjusted risk difference -4.3%, 95% CI -7.8% to -0.7%; p = 0.020). Other outcomes did not differ. DISCUSSION: One in 4 patients with AF and breakthrough ischemic stroke on OAC had competing etiologies, most often large artery atherosclerosis. These patients showed higher risk of recurrent stroke, functional dependence, mortality, and bleeding, highlighting the need for development of individualized secondary prevention. Main study limitations include observational retrospective design and incomplete data on on-treatment anticoagulation quality. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT06823466.
引用
- Foschi M, De Santis F, Gabriele F, et al. Competing Stroke Etiologies and Outcomes After Breakthrough Ischemic Stroke on Oral Anticoagulants in Patients With Atrial Fibrillation. Neurology. 2026. PMID: 41974022. doi:10.1212/WNL.0000000000214758
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。