阿加曲班联合双联抗血小板治疗分支动脉粥样硬化疾病的效果：一项随机临床试验

Effect of Argatroban Plus Dual Antiplatelet in Branch Atherosclerosis Disease: A Randomized Clinical Trial.

作者信息

Xu Jinghan, Liu Yinglin, Wang Huazedan, Sun Rong, Zhao Hongjian, Liu Xindong, Li Yuanyuan, Yang Juan, Zhang Bei, He Lanying, Gong Liang, Ding Xin, Xu Xuejun, Xu Ronghua, Wang Jian

机构信息

Department of Neurology (J.X., Y. Liu, H.W., R.S., B.Z., L.H., L.G., X.D., J.W.), Chengdu Second People's Hospital, China.

School of Clinical Medicine, Chengdu Medical College, China (R.S.).

出版信息

Stroke. 2025 Jul;56(7):1662-1670. doi: 10.1161/STROKEAHA.124.048872. Epub 2025 Apr 17.

DOI:10.1161/STROKEAHA.124.048872

PMID:40242875

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12180705/

Abstract

BACKGROUND

Branch atherosclerosis disease (BAD) is prone to early neurological deterioration (END). The purpose of this study was to assess the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) for preventing END in high-risk branch atherosclerosis disease patients.

METHODS

This multicenter, open-label, blinded end point, randomized controlled trial including branch atherosclerosis disease patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) was conducted at 4 centers in China from May 18, 2021 to February 8, 2023. Within 48 hours after symptom onset, patients were randomly assigned to receive argatroban plus DAPT or DAPT alone in a 1:1 ratio. The primary end points were the incidence of END (National Institutes of Health Stroke Scale score increase ≥2) within 7 days and excellent functional outcome (modified Rankin Scale score of 0 to 1) at 90 days.

RESULTS

A total of 111 patients were randomized, with 11 excluded for specific reasons, resulting in 100 patients included in the modified intention-to-treat population. Among the 100 patients, 49 received argatroban plus DAPT and 51 received DAPT alone, 63 (63.0%) were men, and the median age was 64 (range, 55-74) years. END occurred in 20.4% (10/49) of the argatroban plus DAPT group and 47.1% (24/51) of the DAPT group (risk difference, 26.7% [95% CI, 14.1-39.2]; risk ratio, 2.31 [95% CI, 1.49-3.58]; =0.006). At the 90-day follow-up, 87.8% (43/49) in the argatroban plus DAPT group and 68.6% (35/51) in the DAPT group achieved an excellent functional outcome (risk difference, -19.1% [95% CI, -30.3 to -8.0]; risk ratio, 0.78 [95% CI, 0.67-0.91]; =0.025). There was 1 minor hemorrhage in each group.

CONCLUSIONS

Argatroban plus DAPT is a safe and effective strategy to reduce END occurrence and improve 90-day functional outcome in high-risk branch atherosclerosis disease patients.

REGISTRATION

URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR21000 46487.

摘要

背景

分支动脉粥样硬化疾病（BAD）易导致早期神经功能恶化（END）。本研究旨在评估阿加曲班联合双联抗血小板治疗（DAPT）预防高危分支动脉粥样硬化疾病患者发生END的有效性和安全性。

方法

本多中心、开放标签、盲法终点、随机对照试验纳入了轻度卒中（美国国立卫生研究院卒中量表评分≤5）的分支动脉粥样硬化疾病患者，于2021年5月18日至2023年2月8日在中国的4个中心进行。症状发作后48小时内，患者按1:1比例随机分配接受阿加曲班联合DAPT或单纯DAPT治疗。主要终点为7天内END的发生率（美国国立卫生研究院卒中量表评分增加≥2）和90天时良好的功能结局（改良Rankin量表评分为0至1）。

结果

共111例患者被随机分组，11例因特定原因被排除，最终100例患者纳入改良意向性分析人群。100例患者中49例接受阿加曲班联合DAPT治疗，51例接受单纯DAPT治疗，男性63例（63.0%），中位年龄为64岁（范围55 - 74岁）。阿加曲班联合DAPT组END发生率为20.4%（10/49），单纯DAPT组为47.1%（24/51）（风险差异26.7% [95%CI，14.1 - 39.2]；风险比2.31 [95%CI，1.49 - 3.58]；P = 0.006）。90天随访时，阿加曲班联合DAPT组87.8%（43/49）患者获得良好功能结局，单纯DAPT组为68.6%（35/51）（风险差异-19.1% [95%CI，-30.3至-8.0]；风险比0.78 [95%CI，0.67 - 0.91]；P = 0.025）。每组各有1例轻度出血。