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Long B, Gottlieb M. Intravenous thrombolysis for minor acute ischemic stroke. Academic Emergency Medicine. 2026;33(1):e70148. doi:10.1111/acem.70148

Study Population: 3364 participants ≥18 years with minor ischemic stroke

Efficacy Endpoints

Excellent recovery (modified Rankin scale 0–1), favorable outcome (modified Rankin scale 0–2)

Harm Endpoints

Mortality within 3 months

Narrative

Acute ischemic stroke (AIS) is a significant cause of disability and mortality. Minor strokes, with a NIH Stroke Scale (NIHSS) ≤ 5, comprise over 50% of AIS1^, 2^, 3, and up to one-third of patients experience functional impairment within 90 days due to evolving or recurrent stroke3^, 4^, 5^, 6. Guidelines therefore suggest intravenous thrombolysis for minor AIS with disabling symptoms7^, 8. Here we summarize a systematic review assessing the safety and efficacy of intravenous thrombolysis added to standard care in patients with minor AIS9.

The review and meta-analysis data summarized here include 4 trials of 3364 adult participants with minor AIS randomized to standard care with or without thrombolysis9. While the review authors collected data from trials enrolling exclusively minor AIS patients, they also extracted and reported on some data examining minor AIS subgroups from trials that enrolled patients with a broad spectrum of AIS severities. For this summary, we focused on comparisons from trials enrolling only minor AIS patients. The review authors defined minor AIS as NIHSS ≤ 5, regardless of whether symptoms were considered disabling. The age of included patients ranged from 56 to 80 years, and thrombolytic drugs used in the trials included alteplase, tenecteplase, and pro-urokinase.

The primary endpoint of interest was excellent outcome at 3 months, defined as a modified Rankin scale (mRS) score 0 to 1. Secondary endpoints included favorable outcome at 90 days (mRS score 0–2), mortality at 3 months, and recurrent stroke. Safety outcomes included intracranial hemorrhage. However, because we have focused on final neurologic status as measured by mRS, any clinical impact of intracranial hemorrhage is integrated into this final assessment. Therefore, the review does not report intracranial hemorrhage separately from mRS.

The systematic review reported no improvement in excellent recovery with thrombolysis (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.7 to 1.03)9. Thrombolysis did, however, appear to lower the odds of 90-day independence (OR: 0.7; 95% CI: 0.6 to 0.99; absolute risk difference [ARD] 2.5%; number-needed-to-harm [NNH]: 40) and increase mortality (OR: 2.4; 95%: CI 1.2 to 4.7; ARD: 1.5%; NNH: 66). There was no difference in recurrent stroke. The results were unaffected or minimally affected by inclusion of subgroup data from trials enrolling patients with a variety of stroke severities9.

Caveats

There are important limitations to this review9. First, the level of heterogeneity among the trials was high. The included RCTs had differing definitions of disabling symptoms, agents, time windows for treatment, routine care strategies, concomitant interventions, and follow-up times. These differences may arguably challenge the validity of statistically pooling the results. Second, participants experiencing strokes presenting with isolated dysarthria, ataxia, facial weakness, sensory symptoms, and other isolated symptoms not captured by the NIHSS were not enrolled. Third, other advanced treatments like endovascular therapy were not evaluated10. While all RCTs were assessed as having low risk of bias, there were concerns regarding data completeness and baseline imbalances.

In summary, thrombolysis worsened 90-day independence and increased mortality in trial participants with minor AIS. Thus, we have assigned a color of Black (Harm > Benefit).

Despite its widespread use, thrombolysis for ASI remains controversial11, particularly after scrutiny of the NINDS and ECASS trials' data12^, 13. This systematic review supports the need for further research through well-designed large multicenter trials to assess its efficacy or identify specific populations that may benefit from it.

AEM: The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Brit Long, MD; Michael Gottlieb, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

February 12, 2026