Exploring Between-Study Heterogeneity in Extended-Window IV Thrombolysis for Acute Ischemic Stroke

作者：Mohamed Fahmy Doheim, Abdullah M. Al-Qudah, Romil Singh, Nirav Bhatt, Marcelo Rocha, Lawrence R. Wechsler, Gaoting Ma, Gisele Sampaio Silva, Sheila Cristina Ouriques Martins, Chunrong Tao, Junwei Hao, Yamei Tang, Wei Hu, Lee H. Schwamm, Thanh N. Nguyen, Raul G. Nogueira · 发表于：Neurology · 年份：2026 · DOI：10.1212/wnl.0000000000218331 · 被引用次数：1 · 研究领域：Acute Ischemic Stroke Management、Acute Myocardial Infarction Research、Blood Coagulation and Thrombosis Mechanisms

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) is the standard-of-care evidence-based treatment of eligible patients with acute ischemic stroke (AIS) within 4.5 hours of symptom onset. Emerging evidence supports its use beyond this time window, leading to expanded recommendations for selected patients presenting between 4.5 and 24 hours. We performed a systematic review and meta-analysis to evaluate IVT in the 4.5- to 24-hour window and to explore sources of between-study heterogeneity. METHODS: We searched MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception through February 2026. Eligible studies were randomized controlled trials (RCTs) or individual patient-data meta-analyses of RCTs comparing IVT with control in patients with AIS presenting beyond 4.5 hours from last known well. The primary outcome was excellent functional recovery, defined as a modified Rankin Scale (mRS) of 0-1 at 90 days. Secondary outcomes included functional independence (mRS of 0-2 at 90 days); change in mRS disability, quantified as the common odds ratio (OR) for a 1-point improvement across the full ordinal mRS distribution (ordinal analysis); and safety measures such as 90-day mortality and symptomatic intracranial hemorrhage (sICH). Risk ratios (RRs) with 95% CIs were pooled. Multivariable meta-regression simultaneously modeled thrombolytic agent, endovascular thrombectomy context, and territory to disentangle confounded predictors. RESULTS: = 0.032 for mRS 0-2) is the primary driv...