From the Department of Neurology, University Hospital Basel, University of Basel, Basel (U.F., T.K.), the Department of Neurology (U.F., S.A., K.N., M.G., M.A., C. Ferrari, S.B., C.B., D.J.S., T.H.), the Support Center for Advanced Neuroimaging, Institute of Diagnostic and Interventional Neuroradiology (B.J.W.), and the Institute for Diagnostic and Interventional Neuroradiology (S.F., B.R.-K., A.H., J.G.), University Hospital Bern, and CTU Bern (M.B., S.T.), Institute of Social and Preventive Medicine (G.S.), University of Bern, Bern, the Department of Neurology, University Hospital Lausanne, University of Lausanne, Lausanne (P.M., A.S.), the Department of Neurology, Cantonal Hospital Aarau, Aarau (K.N., T.K.), the Research Department, Reha Rheinfelden, Rheinfelden (L.H.B.), and the Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen (J.V.) - all in Switzerland; the Departments of Cerebrovascular Medicine (M. Koga, K.T.) and Neurology (T.Y.), National Cerebral and Cardiovascular Center, Osaka, the Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi (K.M.), and the Department of Neurology, Kansai Medical University, Hirakata (Y.Y.) - all in Japan; the Department of Neurology, Helsinki University Hospital, and University of Helsinki, Helsinki (D.S., M.T., S.R.); Internal, Vascular, and Emergency Medicine, Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia (M.P., D.G.), and the Department of Human Neurosciences, University La Sapienza, Rome (N.C.) - both in Italy; the Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg (G.T.), the Department of Neurology, Heidelberg University Hospital (C.G.), and the Department of Neurology, Medical Faculty Mannheim, University of Heidelberg (A.A.), Heidelberg, the Department of Neurology and Stroke and the Hertie Institute for Clinical Brain Research, Tübingen University, Tübingen (S.P.), and the Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg (C. Fung) - all in Germany; the Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece (G.N.); the Department of Neurology, and the Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz (T.G., M. Kneihsl), and the Department of Neurology 2, Kepler University Hospital, Johannes Kepler University, Linz (C.K.) - both in Austria; the Department of Neurology, Oslo University Hospital (E.-C.S.), the Department of General Practice, University of Oslo (E.K.), and the Norwegian Air Ambulance Foundation (E.-C.S.), Oslo, and the Department of Neurology, Akershus University Hospital, Lørenskog (E.K.) - all in Norway; the Department of Neurology, Mater Misericordiae University Hospital, Dublin (P.K.); KU Leuven, Department of Neurosciences, Experimental Neurology, and the Department of Neurology, University Hospitals Leuven, Leuven (R.L., J. Demeestere), the Department of Neurology, Comprehensive Stroke Unit, CHC MontLégia Hospital, Liège (P.D.), the Department of Neurology, Algemeen Ziekenhuis Groeninge Kortrijk, Kortrijk (P.V.), the Neurovascular Center and Stroke Unit Antwerp, Antwerp University Hospital, and the Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp (P.V.), and the Department of Neurology, Ghent University Hospital, Ghent (D.H.) - all in Belgium; Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India (P.N.S.); the Stroke Center, Lisbon Central University Hospital (D.A.S., A.P.N.) and Faculty of Medicine, University of Lisbon (D.A.S.) - both in Lisbon, Portugal; the Department of Neurology, Shaare Zedek Medical Center, Jerusalem (N.M.B.); the Department of Neurology, Faculty of Medicine, Pavol Jozef Safarik University, and University Hospital Louis Pasteur - both in Košice, Slovakia (Z.G.); Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Rhyl (H.T., R.H.), the Stroke Unit, Morriston Hospital, Swansea Bay University Health Board, Swansea (M. Krishnan, P.S.), the Stroke Department, University Hospital of North Durham, Durham (G.C.S.), the Department of Neurology, St. George's University Hospital (L.Z.), and the Stroke Research Centre, Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, University College London (D.J.W.), London, and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J. Dawson) - all in the United Kingdom; and the Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, and the Department of Neurology, Sahlgrenska University Hospital - both in Gothenburg, Sweden (T.T.).
N Engl J Med. 2023 Jun 29;388(26):2411-2421. doi: 10.1056/NEJMoa2303048. Epub 2023 May 24.
The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.
We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.
Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.
In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).
在有急性缺血性脑卒中的房颤患者中，与较晚开始直接口服抗凝剂（DOAC）相比，早期开始 DOAC 的效果尚不清楚。
我们在 15 个国家的 103 个地点进行了一项由研究者发起的、开放性标签试验。参与者以 1:1 的比例随机分配至早期抗凝组（在小或中型卒中后 48 小时内，或在大卒中后第 6 或第 7 天）或晚期抗凝组（小卒中后第 3 或第 4 天，中卒 后第 6 或第 7 天，或大卒中后第 12、13 或 14 天）。评估人员对试验分组情况不知情。主要结局是随机分组后 30 天内复发的缺血性卒中、全身性栓塞、主要颅外出血、症状性颅内出血或血管性死亡的复合结局。次要结局包括 30 天和 90 天的复合主要结局的组成部分。
在 2013 名参与者（37%为小卒中，40%为中卒中，23%为大卒中）中，1006 名被分配至早期抗凝组，1007 名被分配至晚期抗凝组。早期治疗组有 29 名（2.9%）参与者发生主要结局事件，晚期治疗组有 41 名（4.1%）参与者发生该事件（风险差异，-1.18 个百分点；95%置信区间[CI]，-2.84 至 0.47）。30 天时，早期治疗组有 14 名（1.4%）参与者发生复发性缺血性卒中，晚期治疗组有 25 名（2.5%）参与者发生该事件（比值比，0.57；95%CI，0.29 至 1.07）；90 天时，早期治疗组有 18 名（1.9%）参与者发生该事件，晚期治疗组有 30 名（3.1%）参与者发生该事件（比值比，0.60；95%CI，0.33 至 1.06）。30 天时，两组各有 2 名（0.2%）参与者发生症状性颅内出血。
在这项试验中，与较晚使用 DOAC 相比，早期使用 DOAC 估计可使 30 天内复发缺血性卒中、全身性栓塞、主要颅外出血、症状性颅内出血或血管性死亡的发生率降低 2.8 个百分点至升高 0.5 个百分点（基于 95%CI）。（由瑞士国家科学基金会等资助；ELAN ClinicalTrials.gov 编号，NCT03148457。）
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