Safety of Factor XI Inhibition With Abelacimab in Atrial Fibrillation by Kidney Function: A Prespecified Analysis of the AZALEA-TIMI 71 Randomized Clinical Trial.

In the AZALEA-TIMI 71 randomized clinical trial, abelacimab, a novel factor XI inhibitor, reduced rates of major or clinically relevant nonmajor (CRNM) bleeding compared with rivaroxaban in patients with AF.

在AZALEA-TIMI 71随机临床试验中，新型因子XI抑制剂abelacimab与利伐沙班相比，降低了房颤患者的严重或临床相关的非主要（CRNM）出血率。

Background

To examine the safety of abelacimab vs rivaroxaban across a range of kidney function.

为了检查不同肾功能范围内abelacimab与rivaroxaban的安全性。

DESIGN, SETTING, AND PARTICIPANTS: The AZALEA-TIMI 71 study randomized patients with AF to 1 of 2 abelacimab doses (150 mg or 90 mg monthly) or to rivaroxaban, with stratification by creatinine clearance (CrCl).

设计、环境和参与者：AZALEA-TIMI 71研究将房颤患者随机分配到2种abelacimab剂量（每月150毫克或90毫克）或rivaroxaban，按肌酐清除率（CrCl）进行分层。

Patients with CrCl less than 15 mL/min or receiving dialysis were excluded.

排除了肌酐清除率小于15 mL/min或正在接受透析的患者。

This secondary analysis of AZALEA-TIMI 71 examines outcomes by randomized treatment and CrCl at randomization.

这项对AZALEA-TIMI 71的次要分析，通过随机治疗和随机化时的肌酐清除率来检查结果。

intervention

Patients randomized to rivaroxaban with a CrCl greater than 50 mL/min received rivaroxaban, 20 mg, daily, and those with a CrCl of 50 mL/min or less received rivaroxaban, 15 mg, daily.

随机分配到利伐沙班治疗的患者，若肌酐清除率（CrCl）大于50 mL/min，则每日接受20 mg利伐沙班；若CrCl为50 mL/min或以下，则每日接受15 mg利伐沙班。

Patients randomized to abelacimab received the assigned dose irrespective of CrCl.

随机分配到阿贝西单抗治疗的患者，无论其肌酐清除率（CrCl）如何，均接受指定剂量。

main_outcomes_and_measure

The primary outcome was major bleeding or CRNM bleeding.

主要结果是重大出血或临床相关非重大出血。

Results

Among 1284 patients, median (IQR) age was 74 (69-78) years and 572 patients (44.5%) were female.

在1284名患者中，中位年龄为74岁（四分位数间距为69-78岁），572名患者（占44.5%）为女性。

Median (IQR) CrCl was 71 (54-90) mL/min, with 264 patients (20.6%) having a CrCl of 50 mL/min or less.

中位数（四分位数间距）CrCl为71（54-90）mL/min，有264名患者（20.6%）的CrCl为50 mL/min或以下。

In the rivaroxaban group, patients with CrCl of 50 mL/min or less experienced higher rates of major or CRNM bleeding compared with those with CrCl greater than 50 mL/min despite dose reduction (incidencerates, 13.6 vs 7.0 per 100 person-years).

在利伐沙班组中，CrCl为50 mL/min或以下的患者在剂量减少的情况下，与CrCl大于50 mL/min的患者相比，发生主要或CRNM出血的比率较高（发生率，每100人年为13.6比7.0）。

Abelacimab reduced major or CRNM bleeding vs rivaroxaban irrespective of CrCl (CrCl ≤50 mL/min: hazard ratio[HR], 0.26; 95% CI, 0.12-0.54; >50 mL/min: HR, 0.40; 95% CI, 0.26-0.62; P value for interaction = .33), with absolute risk reductions of 10.1 vs 4.2 per 100 person-years in those with CrCl of 50 mL/min or less vs greater than 50 mL/min, respectively (P value for interaction = .09).

与利伐沙班相比，Abelacimab无论肾小球滤过率（CrCl ≤50 mL/min: 风险比[HR]，0.26; 95% 置信区间，0.12-0.54; >50 mL/min: HR, 0.40; 95% 置信区间，0.26-0.62; 交互作用P值= .33)，在CrCl ≤50 mL/min与>50 mL/min的患者中，绝对风险降低分别为每100人年10.1与4.2（交互作用P值= .09）。

This risk reduction was consistent for major bleeding alone and for a broader composite inclusive of major, CRNM, and minor bleeding.

这种风险降低对于单独的主要出血和包括主要、CRNM和轻微出血在内的更广泛复合指标是一致的。

Results were similar when comparing the individual abelacimab doses to rivaroxaban.

在比较各个剂量的abelacimab与rivaroxaban时，结果相似。

conclusions_and_relevance

In this secondary analysis of the AZALEA-TIMI 71 randomized clinical trial, abelacimab consistently reduced the risk of bleeding relative to rivaroxaban irrespective of kidney function.

在这项AZALEA-TIMI 71随机临床试验的次要分析中，abelacimab相对于利伐沙班一致地降低了出血风险，且不受肾功能影响。

These findings suggest that abelacimab may offer a particularly favorable safety profile among those with chronic kidney disease; however, larger studies are necessary to characterize the efficacy of abelacimab for stroke prevention in AF.

这些发现表明，对于慢性肾脏病患者，abelacimab可能提供特别有利的安全性；然而，需要更大规模的研究来确定abelacimab在房颤中预防中风的疗效。