BACKGROUND 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. METHODS 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. RESULTS 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 CHA2DS2-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. CONCLUSIONS 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.).

中文翻译：

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Asundexian 与 Apixaban 在心房颤动患者中的比较。


背景 对心房颤动患者使用直接口服抗凝剂预防中风会带来出血风险并限制其使用。Asundexian 是一种活化的因子 XI （XIa） 抑制剂，是一种口服抗凝剂，可预防中风且出血较少。方法 在一项 3 期国际双盲试验中，我们以 1：1 的比例随机分配高危心房颤动患者接受剂量为 50 mg 的 asundexian 每日一次或标准剂量的阿哌沙班。主要疗效目标是确定 asundexian 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 asundexian 在主要出血事件方面是否优于阿哌沙班。结果 意向治疗人群共纳入 14,810 例随机分配的患者。患者的平均 （±SD） 年龄为 73.9±7.7 岁，35.2% 为女性，18.6% 患有慢性肾病，18.2% 既往有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 CHA2DS2-VASc 评分 （范围为 0 至 9，评分越高表示中风风险越高） 为 4.3±1.3。在独立数据监测委员会的建议下，该试验提前终止。98 例 （1.3%） 接受 asundexian 治疗的患者和 26 例 （0.4%） 接受阿哌沙班治疗的患者发生卒中或全身性栓塞 （风险比，3.79;95% 置信区间 [CI]，2.46 至 5.83）。接受 asundexian 治疗的 17 例患者 （0.2%） 和接受阿哌沙班治疗的 53 例 （0.7%） 患者发生大出血 （风险比，0.32;95% CI，0.18 至 0.55）。两组不良事件的发生率似乎相似。 结论 在有中风风险的心房颤动患者中，在试验提前停止前，与阿哌沙班治疗相比，每天一次剂量的 asundexian 治疗与中风或全身性栓塞的发生率相关。在此期间，asundexian 的主要出血事件少于 apixaban 。（由拜耳资助;OCEANIC-AF ClinicalTrials.gov 编号，NCT05643573;EudraCT 编号，2022-000758-28。