Journal-based CME Course: Intravenous Thrombolysis Beyond the Conventional Time Window for Acute Ischemic Stroke – A Systematic Review and Meta-Analysis

Activity ID

15138

Expires

September 17, 2029

Format Type

Journal-based

CME Credit

1

Fee

$30

CME Provider: JAMA Network Open

Description of CME Course

Importance  Intravenous thrombolysis (IVT) is an established therapy for acute ischemic stroke when administered within 4.5 hours of symptom onset. However, many patients present beyond this window or with unknown onset, and recent randomized clinical trials (RCTs) have evaluated whether imaging-selected patients may benefit from thrombolysis in the extended window.

Objective  To evaluate the functional and safety outcomes associated with IVT administered 4.5 hours or more after stroke onset.

Data Sources  PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from database inception through March 3, 2026.

Study Selection  RCTs enrolling adults with acute ischemic stroke treated with IVT 4.5 hours or more after symptom onset were included. Trials comparing thrombolysis with placebo or standard medical care and reporting functional or safety outcomes were eligible.

Data Extraction and Synthesis  Data were extracted independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk ratios (RRs) and mean differences with 95% CIs were pooled using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool.

Main Outcomes and Measures  Primary outcomes were excellent functional outcome (modified Rankin scale scores of 0-1 at 90 days), good functional outcome (modified Rankin scale scores of 0-2 at 90 days), all-cause 90-day mortality, and symptomatic intracerebral hemorrhage (ICH).

Results  Fourteen RCTs including 4174 patients (2102 in the thrombolysis group and 2072 in the control group) were analyzed, 9 of which were published within the past 5 years. IVT was associated with a higher likelihood of excellent functional outcome (RR, 1.22; 95% CI, 1.14-1.31) and good functional outcome (RR, 1.12; 95% CI, 1.06-1.18) at 90 days. Mortality did not differ between groups (RR, 1.13; 95% CI, 0.93-1.38), but thrombolysis was associated with an increased the risk of symptomatic ICH (RR, 2.44; 95% CI, 1.45-4.09). Absolute treatment effects corresponded to a number needed to treat of 12 to 16 for an additional favorable outcome and a number needed to harm of 62 for symptomatic ICH.

Conclusions and Relevance  In this systematic review and meta-analysis of 14 RCTs, IVT administered beyond 4.5 hours after stroke onset was associated with improved functional outcomes despite an increased risk of symptomatic ICH, supporting extension of thrombolytic therapy beyond the conventional treatment window in appropriately imaging-selected patients.

Disclaimers

1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.

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