Doheim Mohamed F, Nguyen Thanh N, Xiong Yunyun, Chen Hui-Sheng, Bhatt Nirav R, Wang Yongjun, Nogueira Raul G
UPMC Stroke Institute, Department of Neurology, University of Pittsburgh School of Medicine, PA.
Departments of Neurology and Radiology, Boston Medical Center, MA.
Neurology. 2025 Aug 12;105(3):e213863. doi: 10.1212/WNL.0000000000213863. Epub 2025 Jul 17.
The therapeutic efficacy and safety of IV thrombolysis (IVT) for patients with minor strokes remain a subject of significant debate and uncertainty. This meta-analysis aimed to assess the comparative effectiveness and safety of IVT vs nonthrombolytic standard of care (NT-SC) in minor strokes, focusing exclusively on data from randomized controlled trials (RCTs).
A comprehensive literature search was conducted to identify RCTs evaluating IVT in minor stroke, defined as a NIH Stroke Scale (NIHSS) score ≤5. The primary outcome was excellent functional recovery, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary outcomes included functional independence (mRS 0-2 at 90 days) and safety end points, including 90-day mortality, recurrent stroke, symptomatic intracranial hemorrhage (sICH), and any ICH. The study was registered with PROSPERO (CRD42024621714).
The primary analysis included data from 4 RCTs that exclusively enrolled patients with minor stroke (N = 3,364; age range: 56-80 years). Secondary analyses incorporated post hoc and subgroup data on patients with minor stroke from earlier RCTs. In the primary analysis, IVT was not significantly associated with higher odds of excellent functional recovery at 90 days compared with NT-SC (mRS 0-1; odds ratio [OR] 0.85, 95% CI 0.70-1.03). IVT was significantly associated with lower odds of achieving 90-day functional independence (mRS 0-2; OR 0.71, 95% CI 0.55-0.91) and higher odds of both sICH (OR 5.22, 95% CI 1.76-15.48) and 90-day mortality (OR 2.40, 95% CI 1.23-4.67) compared with NT-SC. Subgroup analysis showed a nonsignificant association of IVT with odds of excellent functional recovery across both groups with disabling symptoms (OR 0.84, 95% CI 0.38-1.88) and nondisabling symptoms (OR 0.82, 95% CI 0.66-1.03). The pooled analysis, which incorporated nonoverlapping subgroups and post hoc data, yielded consistent findings.
The findings suggest that IVT does not confer improved functional outcomes among patients with minor strokes and can be associated with higher odds of sICH and mortality at 90 days compared with NT-SC. Since most of the included patients presented with nondisabling minor strokes, additional studies on patients with mildly disabling symptoms are warranted.
静脉溶栓（IVT）治疗轻度卒中患者的疗效和安全性仍是一个存在重大争议且不确定的问题。本荟萃分析旨在评估IVT与非溶栓标准治疗（NT-SC）在轻度卒中治疗中的相对有效性和安全性，仅关注随机对照试验（RCT）的数据。
进行了全面的文献检索，以识别评估IVT治疗轻度卒中（定义为美国国立卫生研究院卒中量表[NIHSS]评分≤5）的RCT。主要结局为良好的功能恢复，定义为90天时改良Rankin量表（mRS）评分为0-1。次要结局包括功能独立（90天时mRS为0-2）和安全性终点，包括90天死亡率、复发性卒中、症状性颅内出血（sICH）和任何颅内出血。该研究已在国际前瞻性系统评价注册库（PROSPERO）注册（注册号：CRD42024621714）。
主要分析纳入了4项专门招募轻度卒中患者的RCT数据（N = 3364；年龄范围：56-80岁）。次要分析纳入了早期RCT中轻度卒中患者的事后分析和亚组数据。在主要分析中，与NT-SC相比，IVT在90天时与良好功能恢复的较高几率无显著关联（mRS 0-1；优势比[OR] 0.85，95%置信区间[CI] 0.70-1.03）。与NT-SC相比，IVT与90天实现功能独立的较低几率（mRS 0-2；OR 0.71，95% CI 0.55-0.91）以及sICH（OR 5.22，95% CI 1.76-15.48）和90天死亡率（OR 2.40，95% CI 1.23-4.67）的较高几率显著相关。亚组分析显示，IVT与有残疾症状组（OR 0.84，95% CI 0.38-1.88）和无残疾症状组（OR 0.82，95% CI 0.66-1.03）良好功能恢复几率的关联均不显著。纳入非重叠亚组和事后分析数据的汇总分析得出了一致的结果。
研究结果表明，与NT-SC相比时，IVT并未使轻度卒中患者的功能结局得到改善，且可能与90天时sICH和死亡率的较高几率相关。由于大多数纳入患者表现为无残疾的轻度卒中，因此有必要对有轻度残疾症状的患者进行更多研究。
