Abelacimab vs Rivaroxaban in Older Individuals With Atrial Fibrillation: A Prespecified Analysis of the Phase 2b AZALEA-TIMI 71 Trial.

Factor XI (FXI) inhibition may offer a safer anticoagulant strategy in this population.

FXI（因子XI）的抑制可能为这一人群提供一种更安全的抗凝策略。

Background

To evaluate the safety of the novel FXI inhibitor abelacimab vs rivaroxaban by age in patients with atrial fibrillation (AF).

评估新型FXI抑制剂abelacimab与rivaroxaban在房颤患者中的安全性，按年龄分层。

DESIGN, SETTING, AND PARTICIPANTS: The randomized clinical trial AZALEA-TIMI 71 randomized patients with AF to receive 1 of 2 subcutaneous abelacimab doses (90 mg or 150 mg monthly) or oral rivaroxaban (20 mg daily, dose reduction to 15 mg).

设计、环境和参与者：随机临床试验AZALEA-TIMI 71将房颤患者随机分配接受两种皮下abelacimab剂量（每月90毫克或150毫克）或口服rivaroxaban（每日20毫克，剂量可减至15毫克）。

This prespecified analysis of the phase 2b AZALEA-TIMI 71 trial evaluated bleeding risk by age, analyzed continuously and categorically (<75 vs ≥75 years).

这项预先指定的 AZALEA-TIMI 71 期 2b 试验分析评估了按年龄划分的出血风险，连续分析和分类分析（<75 岁与≥75 岁）。

The trial was conducted from March 2021 to September 2023; data analysis was performed from February to May 2025.

该试验从2021年3月进行到2023年9月；数据分析是从2025年2月到5月进行的。

Methods

Monthly subcutaneous abelacimab (90 or 150 mg) or daily oral rivaroxaban (20/15 mg).

每月皮下注射阿贝拉西莫（90或150毫克）或每日口服利伐沙班（20/15毫克）。

main_outcomes_and_measures

The primary end point was the composite of major or clinically relevant nonmajor (CRNM) bleeding.

主要终点是主要或临床相关的非主要（CRNM）出血的复合事件。

Results

Among 1287 patients randomized, 715 (55.6%) were male and 572 (44.4%) were female; there were 625 patients (49%) 75 years or older.

在随机分配的1287名患者中，715名（55.6%）为男性，572名（44.4%）为女性；有625名患者（49%）年龄在75岁或以上。

Compared with younger patients, those 75 years or older had lower body mass index (28 vs 32), were less likely to be taking antiplatelet therapy at baseline (17% vs 32%), and were more likely to have creatinine clearance 50 mL/min or less (33% vs 8%).

与年轻患者相比，75岁或以上的患者体重指数较低（28对比32），基线时服用抗血小板治疗的可能性较小（17%对比32%），且有50 mL/min或以下的肌酐清除率的可能性较大（33%对比8%）。

Both abelacimab doses were associated with significantly less major or CRNM bleeding compared with rivaroxaban in those 75 years or older (hazard ratio[HR], 0.32; 95% CI, 0.17-0.60; and HR, 0.40; 95% CI, 0.22-0.73; for abelacimab, 90 and 150 mg, vs rivaroxaban, respectively) and in those younger than 75 years (HR, 0.28; 95% CI, 0.12-0.61; and HR, 0.35; 95% CI, 0.17-0.70; P for interaction, .85 and .84, respectively).

在75岁或以上的患者中，两种剂量的abelacimab与利伐沙班相比，主要或CRNM出血显著减少（风险比[HR]，0.32；95%置信区间，0.17-0.60；和HR，0.40；95%置信区间，0.22-0.73；对于abelacimab，90毫克和150毫克，与利伐沙班相比），在75岁以下的患者中也是如此（HR，0.28；95%置信区间，0.12-0.61；和HR，0.35；95%置信区间，0.17-0.70；交互作用P值分别为.85和.84）。

Patients 75 years or older tended to derive greater absolute risk reductions with abelacimab (7.1 and 6.2 per 100 patient-years for abelacimab, 90 and 150 mg, vs rivaroxaban, respectively) than those younger than 75 years (4.7 and 4.2 per 100 patient-years, respectively).

75岁或以上的患者倾向于从abelacimab中获得更大的绝对风险降低（对于abelacimab，90毫克和150毫克，分别为每100患者年7.1和6.2，与利伐沙班相比），而75岁以下的患者则分别为每100患者年4.7和4.2。

When modeled continuously, bleeding risk tended to increase with age in the rivaroxaban group but remained stable in the abelacimab group (P for interaction, .33).

当连续建模时，出血风险随着利伐沙班组年龄的增长而倾向于增加，而在阿贝西单抗组中保持稳定（交互作用P值为.33）。

conclusions_and_relevance

This study found that abelacimab consistently reduced bleeding compared with rivaroxaban regardless of age, with the potential for a greater absolute reduction in bleeding with older age.

该研究发现，无论年龄如何，阿贝西单抗与利伐沙班相比始终能降低出血风险，且随着年龄的增长，出血的绝对减少量可能更大。

FXI inhibition with abelacimab may become a particularly attractive option in older patients with AF and higher bleeding risk.

使用 abelacimab 抑制 FXI 可能成为老年房颤患者和高出血风险患者的一个特别有吸引力的选择。

The results of ongoing phase 3 trials are necessary to establish the efficacy and benefit-to-risk ratio of abelacimab.

正在进行的第三阶段试验结果对于确定 abelacimab 的疗效和风险效益比是必要的。

trial_registration

ClinicalTrials.gov Identifier: NCT04755283.

临床试验注册号：NCT04755283。