Intravenous thrombolysis with tenecteplase versus alteplase in acute ischemic stroke tandem occlusions: a systematic review and meta-analysis of current available literature

Tandem occlusions, characterized by the simultaneous occurrence of both extracranial and ipsilateral intracranial arterial occlusions, represents a challenging subset of large vessel occlusion (LVO) strokes. Currently, the treatment choice for tandem infarcts involves intravenous thrombolysis (IVT) followed by endovascular thrombectomy (EVT). In current literature, direct head-to-head comparisons between Alteplase and Tenecteplase for IVT in patients with tandem occlusions remain limited. The goal of this systematic review and meta-analysis is to synthesize the currently available data comparing the efficacy and safety profiles of alteplase and tenecteplase specifically in patients with tandem occlusions. We systematically searched PubMed, Embase and Cochrane from inception to June 2024 for studies enrolling patients with tandem lesions in acute ischemic stroke (AIS) treated with IVT involving Tenecteplase or Alteplase. The primary outcomes of interest were (1) modified Rankin Scale (mRS) 0-1, (2) modified Rankin Scale (mRS) 0-2, (3) successful recanalization (TICI 2b-3), (4) symptomatic intracranial hemorrhage (sICH) and (5) overall mortality. We compared the results using Risk Ratio (RR) with 95% Confidence Intervals (CI). A random effects model was applied for all outcomes. The Mantel-Haenszel method was used to pool results from individual studies. We also used I2 statistics and Cochran Q test to verify heterogeneity. Three studies published between 2023 and 2024 were included, two randomized controlled trials (RCTs) and one observational study, comprising 917 patients. Tenecteplase was administered for 230 (25,1%) patients. The age ranged from 57 to 82 years, the baseline NIHSS ranged from 10 to 24 points and there were 314 (34.2%) female patients in total. There was no statistically significant difference between groups for the outcomes of mRS 0-1 (RR 0.80; 95% CI 0.35 to 1.83; p = 0.597; I2 = 86%), mRS 0-2 (RR 1.04; 95% CI 0.88 to 1.23; p = 0.630; I2 = 0%), TICI 2b-3 (RR 1.00; 95% CI 0.93 to 1.09; p = 0.909; I2 = 0%), sICH (RR 1.09; 95% CI 0.64 to 1.84; p = 0.756; I2 = 0%), and overall mortality (RR 0.68; 95% CI 0.45 to 1.05; p = 0.081; I2 = 17%). This meta-analysis found that tenecteplase achieved similar outcomes to alteplase in improving functional outcomes and recanalization rates. Additionally, there was no significant difference between tenecteplase and alteplase in terms of rates of sICH and mortality. Further large-scale randomized studies are urgently needed to provide a definitive conclusion on the comparative efficacy and safety of tenecteplase versus alteplase in tandem occlusions.