Polymeris Alexandros A, Koga Masatoshi, Strbian Daniel, Vedamurthy Adhiyaman, Krishnan Manju, Branca Mattia, Horvath Thomas, Goeldlin Martina, Shim Gek, Gumbinger Christoph, Zhang Liqun, Kristoffersen Espen Saxhaug, Desfontaines Philippe, Vanacker Peter, Alonso Angelika, Poli Sven, Nunes Ana Paiva, Caracciolo Nicoletta G, Kneihsl Markus, Kahles Timo, Giudici Daria, Räty Silja, Tiainen Marjaana, Dawson Jesse, Fischer Urs
Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
J Stroke. 2025 May;27(2):217-227. doi: 10.5853/jos.2024.04322. Epub 2025 May 31.
Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.
A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.
Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66-1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65-1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30-1.08], HRweighted 0.57 [0.30-1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56-6.63], HRweighted 1.88 [0.56-6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.
Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
在与心房颤动（AF）相关的急性缺血性卒中后开始使用直接口服抗凝剂（DOACs）之前，经常会使用抗血小板药物，但证据不足。在此，我们探讨了这种方法的风险与益处。
对ELAN（心房颤动缺血性卒中患者直接口服抗凝剂早期与晚期启动）试验数据（NCT03148457）进行事后分析，以比较在AF相关缺血性卒中后启动DOAC之前使用和未使用抗血小板药物的参与者在30天内复发性缺血性卒中、全身性栓塞、大出血（颅外或颅内出血[ICH]）和血管性死亡的风险（作为综合结局和个体结局）。我们在治疗加权逆概率模型中使用逻辑回归和特定病因的Cox比例风险回归来解释混杂因素。通过从抗血小板药物可能预防的缺血性事件发生率中减去抗血小板药物导致的出血事件加权发生率，计算使用抗血小板药物的净益处。
在2013名参与者（中位年龄77岁，45.5%为女性）中，1090名（54.1%）使用了抗血小板药物，70名（3.5%）出现了综合结局。使用抗血小板药物与综合结局无关（治疗加权逆概率比值比[ORweighted]为1.06，95%置信区间[CI]为0.66 - 1.72；治疗加权风险比[HRweighted]为1.06，95%CI为0.65 - 1.72），但显示缺血性卒中复发风险较低（ORweighted为0.58[0.30 - 1.08]，HRweighted为0.57[0.30 - 1.10]），大出血风险较高（ORweighted为1.76[0.56 - 6.63]，HRweighted为1.88[0.56 - 6.39]）。对于ICH权重为1.5至3.1，其净益处为每100人月+0.57（95%CI -1.25至+2.34）至+0.30（-1.82至+2.27）加权事件。
在与AF相关的缺血性卒中后，我们发现启动DOAC之前使用抗血小板药物复发风险较低且无净危害迹象，尽管出血风险增加。
