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替罗非班预防颅内动脉狭窄急性缺血性卒中神经功能恶化的效果:TREND试验的事后分析

Effects of tirofiban in preventing neurological deterioration in acute ischemic stroke with intracranial artery stenosis: A post hoc analysis of the TREND Trial.

作者信息

Wang Jing, Qiao Yue, Li Sijie, Li Chuanhui, Wu Chuanjie, Wang Pingping, Yang Ting, Ji Xunming, Ma Qingfeng, Zhao Wenbo

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

Eur Stroke J. 2025 Feb 14:23969873251319151. doi: 10.1177/23969873251319151.

Abstract

INTRODUCTION

The degree of culprit artery stenosis affects the risk of early neurological deterioration (END) after acute ischemic stroke (AIS). The TREND trial demonstrated the efficacy of tirofiban in preventing END in patients with AIS. We aimed to investigate whether the degree of intracranial artery stenosis affects the efficacy of tirofiban in preventing END in patients with AIS.

PATIENTS AND METHODS

We conducted a post hoc analysis of the TREND trial, which enrolled patients within 24 h of onset and randomly allocated to receive intravenous tirofiban or oral aspirin. We stratified the stenosis degrees into three subgroups: no stenosis, mild-to-moderate stenosis (stenosis <70%), and severe stenosis or occlusion (stenosis ⩾70%). The primary endpoint is END defined as an increase of the NIHSS ⩾4 within 72 h after randomization. Secondary outcomes include END (defined as an increase of NIHSS ⩾2) within 72 h after randomization, the proportion of mRS 0-1 and 0-2 at 90 days.

RESULTS

A total of 296 patients were analyzed. In patients with severe stenosis or occlusion, tirofiban significantly reduced the incidence of END (5.7% vs 30.8%, adjusted OR 0.156, 95% CI 0.028-0.873, adjusted  = 0.034), whereas its effects in preventing END were similar to those of aspirin in patients with no stenosis (2.4% vs 4.6%, adjusted OR 0.193, 95% CI 0.018-2.083, adjusted  = 0.175) or mild-to-moderate stenosis (2.9% vs 10.0%, adjusted OR 0.171, 95% CI 0.015-1.943, adjusted  = 0.155). The value for interaction between stenosis subgroups and treatment was 0.513. Furthermore, tirofiban significantly reduced the incidence of END in patients with mild-to-moderate stenosis (5.9% vs 22.5%, OR 0.146, 95% CI 0.022-0.951, adjusted  = 0.044) and severe stenosis or occlusion (11.4% vs 43.6%, adjusted OR 0.140, 95% CI 0.036-0.540, adjusted  = 0.004). A significant improvement in favorable outcomes with a 90-day mRS of 0-1 was observed only in patients with mild-to-moderate stenosis (85.3% vs 70.0%, adjusted OR 4.617, 95% CI 1.077-19.798, adjusted  = 0.039).

DISCUSSION AND CONCLUSION

Tirofiban may significantly reduce the incidence of END in patients with severe arterial stenosis or occlusion. Further studies are required to confirm the effects of intracranial artery stenosis on the benefits of intravenous tirofiban.

TRIAL REGISTRATION

ClinicalTrials.gov; identifier: NCT04491695.

摘要

引言

责任动脉狭窄程度会影响急性缺血性卒中(AIS)后早期神经功能恶化(END)的风险。TREND试验证明替罗非班在预防AIS患者END方面的有效性。我们旨在研究颅内动脉狭窄程度是否会影响替罗非班在预防AIS患者END方面的有效性。

患者与方法

我们对TREND试验进行了事后分析,该试验纳入发病24小时内的患者,并随机分配接受静脉注射替罗非班或口服阿司匹林。我们将狭窄程度分为三个亚组:无狭窄、轻度至中度狭窄(狭窄<70%)和重度狭窄或闭塞(狭窄⩾70%)。主要终点是END,定义为随机分组后72小时内美国国立卫生研究院卒中量表(NIHSS)增加⩾4。次要结局包括随机分组后72小时内的END(定义为NIHSS增加⩾2)、90天时改良Rankin量表(mRS)评分为0 - 1和0 - 2的比例。

结果

共分析了296例患者。在重度狭窄或闭塞的患者中,替罗非班显著降低了END的发生率(5.7%对30.8%,校正比值比0.156,95%置信区间0.028 - 0.873,校正P = 0.034),而在无狭窄(2.4%对4.6%,校正比值比0.193,95%置信区间0.018 - 2.083,校正P = 0.175)或轻度至中度狭窄(2.9%对10.0%,校正比值比0.171,95%置信区间0.015 - 1.943,校正P = 0.155)的患者中,其预防END的效果与阿司匹林相似。狭窄亚组与治疗之间的交互作用P值为0.513。此外,替罗非班显著降低了轻度至中度狭窄(5.9%对22.5%,比值比0.146,95%置信区间0.022 - 0.951,校正P = 0.044)和重度狭窄或闭塞(11.4%对43.6%,校正比值比0.140,95%置信区间0.036 - 0.540,校正P = 0.004)患者的END发生率。仅在轻度至中度狭窄的患者中观察到90天mRS评分为0 - 1的良好结局有显著改善(85.3%对70.0%,校正比值比4.617,95%置信区间1.077 - 19.798,校正P = 0.039)。

讨论与结论

替罗非班可能显著降低重度动脉狭窄或闭塞患者的END发生率。需要进一步研究来证实颅内动脉狭窄对静脉注射替罗非班获益的影响。

试验注册

ClinicalTrials.gov;标识符:NCT04491695。

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