University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland.
Department of Neurology (M. Kneihsl, T.G.), Medical University of Graz, Austria.
Circulation. 2024 Jul 2;150(1):19-29. doi: 10.1161/CIRCULATIONAHA.124.069324. Epub 2024 May 16.
Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown.
This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms.
Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT.
We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH.
URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.
在患有缺血性卒中和心房颤动的人群中，出血性转化（HT）是否会改变早期与晚期开始直接口服抗凝剂的治疗效果尚不清楚。
这是 ELAN 试验（缺血性脑卒中后伴心房颤动患者中早期与晚期直接口服抗凝剂的启动）的事后分析。主要结局是 30 天内复发缺血性脑卒中、症状性颅内出血、主要外出血、全身性栓塞或血管性死亡的复合事件。次要结局是 30 天和 90 天的功能结局。我们根据 HT 进行了结局估计，将其分为预先随机化影像学检查（核心实验室评分）上的出血性梗死（HI）或实质内出血（PH）亚类，并根据治疗组之间的调整风险差异进行分层。
总体而言，1970 名参与者中有 247 名（12.5%）发生 HT（114 例 HI1，77 例 HI2，34 例 PH1，22 例 PH2）。对于主要结局，HT 患者（HI：-4.7%[95%CI，-10.8%至 1.4%]；PH：6.1%[95%CI，-8.5%至 20.6%]）中早期与晚期的估计调整风险差异为-2.2%（95%CI，-7.8%至 3.5%），而无 HT 患者中为-0.9%（95%CI，-2.6%至 0.8%）。有症状性颅内出血的人数在有 HT 和无 HT 的患者中相同。早期治疗时，HT 患者（HI：7.4%[95%CI，-6.4%至 21.2%]；PH：25.1%[95%CI，0.2%至 50.0%]）中 90 天不良功能结局（改良 Rankin 量表评分 3-6）的估计调整风险差异为 11.5%（95%CI，-0.8%至 23.8%），而无 HT 患者中为-2.6%（95%CI，-7.1%至 1.8%）。
我们发现，在有 HT 和无 HT 的患者中，与晚期相比，早期开始直接口服抗凝剂并没有明显的治疗效果差异或安全性问题。然而，早期直接口服抗凝剂的使用可能会使 PH 患者的功能结局恶化。
