Piccini Jonathan P, Patel Manesh R, Steffel Jan, Ferdinand Keith, Van Gelder Isabelle C, Russo Andrea M, Ma Chang-Sheng, Goodman Shaun G, Oldgren Jonas, Hammett Christopher, Lopes Renato D, Akao Masaharu, De Caterina Raffaele, Kirchhof Paulus, Gorog Diana A, Hemels Martin, Rienstra Michiel, Jones W Schuyler, Harrington Josephine, Lip Gregory Y H, Ellis Stephen J, Rockhold Frank W, Neumann Christoph, Alexander John H, Viethen Thomas, Hung James, Coppolecchia Rosa, Mundl Hardi, Caso Valeria
From Duke Clinical Research Institute, Duke University School of Medicine (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, S.J.E., F.W.R., J.H.A.), and Duke University Medical Center (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, F.W.R., J.H.A.) - both in Durham, NC; Hirslanden Clinic Zurich, Zurich, Switzerland (J.S.); the School of Medicine, Tulane University, New Orleans (K.F.); the University Medical Center, University of Groningen, Groningen (I.C.V.G., M.R.), Radboud University Medical Center, Nijmegen (M.H.), Rijnstate Hospital, Arnhem (M.H.), and the Dutch Network for Cardiovascular Research, Utrecht (M.H.) - all in the Netherlands; Cooper Medical School of Rowan University, Camden (A.M.R.), and Bayer U.S., Whippany (R.C.) - both in New Jersey; the Cardiology Center of Beijing, Anzhen Hospital No. 2, Beijing (C.-S.M.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael's Hospital, Unity Health Toronto, and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto - all in Canada (S.G.G.); the Uppsala Clinical Research Center and the Department of Medical Sciences, Uppsala University, Uppsala, Sweden (J.O.); the Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia (C.H.); the Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); the School of Cardiology, University of Pisa, and the Cardiology Division, Pisa University Hospital, Pisa (R.D.C.), and Santa Maria della Misericordia Hospital, University of Perugia, Perugia (V.C.) - all in Italy; the Department of Cardiology, University Heart and Vascular Center Hamburg, and the German Center for Cardiovascular Research, Hamburg (P.K.), and Bayer, Wuppertal (C.N., T.V., H.M.) - all in Germany; the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (P.K.), the Faculty of Medicine, National Heart and Lung Institute, Imperial College, London (D.A.G.), the Centre for Health Services and Clinical Research, Faculty of Life and Medical Sciences, University of Hertfordshire, Hatfield (D.A.G.), and the Liverpool Centre for Cardiovascular Science at University of Liverpool and John Moores University and Liverpool Heart and Chest Hospital, Liverpool (G.Y.H.L.) - all in the United Kingdom; the Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark (G.Y.H.L.); and Bayer, São Paulo (J. Hung).
N Engl J Med. 2025 Jan 2;392(1):23-32. doi: 10.1056/NEJMoa2407105. Epub 2024 Sep 1.
Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.
In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events.
A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHADS-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups.
Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).
在心房颤动患者中使用直接作用口服抗凝剂预防中风存在出血风险，限制了其应用。阿孙地昔，一种活化因子XI（XIa）抑制剂，是一种口服抗凝剂，可能在出血较少的情况下预防中风。
在一项3期国际双盲试验中，我们将高危心房颤动患者按1:1的比例随机分配，分别接受每日一次50mg剂量的阿孙地昔或标准剂量的阿哌沙班。主要疗效目标是确定阿孙地昔在预防中风或全身性栓塞方面是否至少不劣于阿哌沙班。主要安全目标是确定阿孙地昔在主要出血事件方面是否优于阿哌沙班。
共有14810名随机分配的患者纳入意向性分析人群。患者的平均（±标准差）年龄为73.9±7.7岁，35.2%为女性，18.6%患有慢性肾脏病，18.2%有过中风或短暂性脑缺血发作，16.8%接受口服抗凝剂治疗不超过6周，平均CHADS-VASc评分（范围为0至9，分数越高表明中风风险越大）为4.3±1.3。根据独立数据监测委员会的建议，试验提前终止。接受阿孙地昔治疗的98名患者（1.3%）和接受阿哌沙班治疗的26名患者（0.4%）发生了中风或全身性栓塞（风险比，3.79；95%置信区间[CI]，2.46至5.83）。接受阿孙地昔治疗的17名患者（0.2%）和接受阿哌沙班治疗的53名患者（0.7%）发生了主要出血（风险比，0.32；95%CI，0.18至0.55）。两组中任何不良事件的发生率似乎相似。
在有中风风险的心房颤动患者中，在试验提前终止前的这段时间里，每日一次50mg剂量的阿孙地昔治疗与中风或全身性栓塞的发生率高于阿哌沙班治疗相关。在此期间，阿孙地昔的主要出血事件少于阿哌沙班。（由拜耳公司资助；OCEANIC-AF临床试验注册号，NCT05643573；欧盟临床试验注册号，2022-000758-28。）
