替罗非班对急性缺血性脑卒中患者神经功能恶化的影响：一项随机临床试验。

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

机构信息

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, China.

出版信息

JAMA Neurol. 2024 Jun 1;81(6):594-602. doi: 10.1001/jamaneurol.2024.0868.

DOI:10.1001/jamaneurol.2024.0868

PMID:38648030

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11036313/

Abstract

IMPORTANCE

Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes.

OBJECTIVE

To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin.

DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20.

INTERVENTION

Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin.

MAIN OUTCOME

The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization.

RESULTS

A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17).

CONCLUSIONS AND RELEVANCE

In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04491695.

摘要

重要性

有证据支持在急性缺血性脑卒中患者中使用抗血小板治疗。然而，目前推荐的抗血小板治疗方案下，仍有常见的神经功能恶化，导致临床结局较差。

目的

确定与口服阿司匹林相比，在卒中发作后 24 小时内给予静脉注射替罗非班是否可预防急性非心源性脑卒中患者的早期神经功能恶化。

设计、地点和参与者：这是一项由研究者发起、多中心、开放性标签、随机临床试验，采用盲法终点评估，于 2020 年 9 月至 2023 年 3 月在中国的 10 家综合卒中中心进行。纳入的患者为发病 24 小时内的急性非心源性卒中，年龄在 18 至 80 岁之间，NIHSS 评分为 4 至 20 分。

干预措施

患者被随机（1:1）分配接受静脉注射替罗非班或口服阿司匹林治疗 72 小时，采用中央、基于网络的计算机生成随机分组方案；所有患者随后均接受口服阿司匹林治疗。

主要结局

主要疗效结局为随机分组后 72 小时内的早期神经功能恶化（NIHSS 评分增加≥4 分）。主要安全性结局为随机分组后 72 小时内的症状性颅内出血。

结果

共纳入 425 例患者，分别接受静脉注射替罗非班（n=213）或口服阿司匹林（n=212）治疗。中位（IQR）年龄为 64.0 岁（56.0-71.0）；124 例（29.2%）为女性，301 例（70.8%）为男性。替罗非班组有 9 例（4.2%）患者发生早期神经功能恶化，阿司匹林组有 28 例（13.2%）患者发生早期神经功能恶化（调整后的相对风险，0.32；95%CI，0.16-0.65；P=0.002）。替罗非班组无颅内出血病例。90 天随访时，替罗非班组有 3 例（1.3%）患者和阿司匹林组有 3 例（1.5%）患者死亡（调整后的 RR，1.15；95%CI，0.27-8.54；P=0.63），替罗非班组和阿司匹林组的中位（IQR）改良 Rankin 量表评分分别为 1.0（0-1.25）和 1.0（0-2）（调整后的优势比，1.28；95%CI，0.90-1.83；P=0.17）。