Tenecteplase, alteplase, and endovascular thrombectomy in extended-window acute ischemic stroke with intracranial large-vessel occlusion: a Bayesian network meta-analysis.

Abstract

Background and purpose: The comparative effects of intravenous thrombolytic agents, endovascular thrombectomy (EVT), and bridging therapy in imaging-selected patients with acute ischemic stroke treated beyond 4.5 hours remain uncertain. We compared these strategies while distinguishing confirmed large-vessel occlusion (LVO) evidence from broader mixed populations.

Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized trials evaluating reperfusion treatments administered 4.5 to 24 hours after stroke onset or last known well. The primary network included trials requiring confirmed intracranial LVO or basilar artery occlusion (BAO). An anterior-circulation LVO network and an all-available network were examined as sensitivity and exploratory analyses. Bayesian random-effects consistency models estimated odds ratios (ORs) with 95% credible intervals (CrIs). The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days.

Results: Fifteen randomized trials were included, of which 8 contributed to the primary confirmed LVO/BAO network. Compared with placebo or best medical care, EVT significantly improved functional independence (OR, 2.93 [95% CrI, 1.40-6.53]) and excellent functional outcome, defined as mRS 0 to 1 (OR, 2.22 [95% CrI, 1.30-4.11]), reduced 90-day mortality (OR, 0.71 [95% CrI, 0.50-0.98]), and increased trial-defined recanalization or reperfusion at approximately 24 hours (OR, 5.27 [95% CrI, 1.83-16.04]); sICH was also increased (OR, 2.65 [95% CrI, 1.28-5.81]). Compared with EVT, tenecteplase plus EVT showed numerically favorable but statistically inconclusive estimates for functional independence (OR, 1.10 [95% CrI, 0.34-3.52]) and excellent outcome (OR, 1.16 [95% CrI, 0.52-2.64]). Direct pairwise analyses of 2 trials were similarly inconclusive. Tenecteplase alone did not show clear differences from placebo or best medical care. Findings were directionally consistent in the anterior-circulation sensitivity and all-available exploratory networks.

Conclusions: Among imaging-selected patients with confirmed intracranial LVO or BAO treated 4.5 to 24 hours after onset or last known well, EVT had the most consistent evidence of benefit versus placebo or best medical care. Tenecteplase plus EVT showed favorable but imprecise estimates, and neither network nor direct pairwise analyses established superiority over EVT alone. The incremental benefit of bridging tenecteplase remains uncertain.