Meta-Analysis of Randomized Controlled Trials on IV Thrombolysis in Patients With Minor Acute Ischemic Stroke

Abstract

Background and objectives: 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).

Methods: 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).

Results: 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.

Discussion: 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.