瑞士巴塞尔大学医院Urs Fischer团队研究了早期和后期抗凝对心房纤颤患者的疗效与安全性。2023年5月24日出版的《新英格兰医学杂志》发表了这项成果。

与后期直接口服抗凝剂（DOAC）相比，早期使用对患有急性缺血性中风的心房颤动患者的影响尚不清楚。

研究组在15个国家的103个机构进行了一项由研究者发起的开放标签试验。参与者以1:1的比例被随机分配到早期抗凝（轻度或中度中风后48小时内，或重度中风后第6或第7天）或后期抗凝（轻度中风后第3或第4天，中度中风后第6或第7天，或重度中风后第12、13或14天）。评估人员对试验小组任务不知情。主要结局是随机分组后30天内复发性缺血性卒中、全身性栓塞、严重颅外出血、症状性颅内出血或血管死亡的复合结局。次要结局包括第30天和第90天复合主要结局的组成部分。

在2013名参与者中（37%为轻度中风，40%为中度中风，23%为重度中风），1006人被分配进行早期抗凝治疗，1007人被分配后期抗凝治疗。在30天内，早期治疗组的29名参与者（2.9%）和后期治疗组的41名参与者（4.1%）发生了主要结局事件（风险差异为−1.18个百分点）。早期治疗组的14名参与者（1.4%）和后期治疗组的25名参与者（2.5%）在30天内发生复发性缺血性卒中（比值比为0.57），18名参与者（1.9%）和30名参与者（3.1%）在90天内分别发生复发性脑卒中（比值比为0.60）。两组中有2名参与者（0.2%）在30天时出现症状性颅内出血。

研究结果表明，在这项试验中，早期使用DOAC的复发性缺血性卒中、全身性栓塞、严重颅外出血、症状性颅内出血或血管死亡的发生率估计比后期使用DOAC低2.8个百分点至高0.5个百分点。

附：英文原文

Title: Early versus Later Anticoagulation for Stroke with Atrial Fibrillation | NEJM

Author: Urs Fischer, M.D.,, Masatoshi Koga, M.D., Ph.D.,, Daniel Strbian, Ph.D.,, Mattia Branca, Ph.D.,, Stefanie Abend, B.Sc.,, Sven Trelle, M.D.,, Maurizio Paciaroni, M.D.,, Gtz Thomalla, M.D.,, Patrik Michel, M.D.,, Krassen Nedeltchev, M.D.,, Leo H. Bonati, M.D.,, George Ntaios, M.D.,, Thomas Gattringer, Ph.D.,, Else-Charlotte Sandset, Ph.D.,, Peter Kelly, M.D.,, Robin Lemmens, Ph.D.,, P.N. Sylaja, M.D.,, Diana Aguiar de Sousa, Ph.D.,, Natan M. Bornstein, M.D.,, Zuzana Gdovinova, M.D., Ph.D.,, Takeshi Yoshimoto, M.D., Ph.D.,, Marjaana Tiainen, M.D., Ph.D.,, Helen Thomas, R.N.,, Manju Krishnan, M.B., B.S.,, Gek C. Shim, M.B., B.Ch.,, Christoph Gumbinger, M.D.,, Jochen Vehoff, M.D.,, Liqun Zhang, M.D., Ph.D.,, Kosuke Matsuzono, M.D., Ph.D.,, Espen Kristoffersen, M.D., Ph.D.,, Philippe Desfontaines, M.D.,, Peter Vanacker, M.D., Ph.D.,, Angelika Alonso, M.D.,, Yusuke Yakushiji, M.D., Ph.D.,, Caterina Kulyk, M.D.,, Dimitri Hemelsoet, M.D.,, Sven Poli, M.D.,, Ana Paiva Nunes, M.D.,, Nicoletta Caracciolo, M.D.,, Peter Slade, M.B., B.Ch.,, Jelle Demeestere, M.D., Ph.D.,, Alexander Salerno, M.D.,, Markus Kneihsl, M.D., Ph.D.,, Timo Kahles, M.D.,, Daria Giudici, M.D.,, Kanta Tanaka, M.D., Ph.D.,, Silja Rty, M.D., Ph.D.,, Rea Hidalgo, R.N.,, David J. Werring, F.R.C.P., Ph.D.,, Martina Gldlin, M.D.,, Marcel Arnold, M.D.,, Cecilia Ferrari, M.B.A.-I.H.M.,, Seraina Beyeler, Ph.D.,, Christian Fung, M.D.,, Bruno J. Weder, M.D.,, Turgut Tatlisumak, M.D., Ph.D.,, Sabine Fenzl, M.D.,, Beata Rezny-Kasprzak, M.D.,, Arsany Hakim, M.D.,, Georgia Salanti, Ph.D.,, Claudio Bassetti, M.D.,, Jan Gralla, M.D.,, David J. Seiffge, M.D.,, Thomas Horvath, M.D.,, and Jesse Dawson, M.D.

Issue&Volume: 2023-05-24

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

DOI: 10.1056/NEJMoa2303048

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2303048