Different doses of tenecteplase vs. alteplase for acute ischemic stroke within 4.5 hours of symptom onset: a network meta-analysis of randomized controlled trials

Huo Liang; Xue Wang; Xuemei Quan; Shijian Chen; Bin Qin; Shuolin Liang; Qiuhui Huang; Jian Zhang; Zhijian Liang

doi:10.3389/fneur.2023.1176540

Different doses of tenecteplase vs. alteplase for acute ischemic stroke within 4.5 hours of symptom onset: a network meta-analysis of randomized controlled trials

Front Neurol. 2023 Jun 2:14:1176540. doi: 10.3389/fneur.2023.1176540. eCollection 2023.

Authors

Huo Liang^#¹, Xue Wang^#¹, Xuemei Quan², Shijian Chen¹, Bin Qin¹, Shuolin Liang¹, Qiuhui Huang¹, Jian Zhang¹, Zhijian Liang¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
² Department of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

^# Contributed equally.

Abstract

Background: The optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset.

Methods: Literature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA).

Results: Eleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes.

Conclusions: The NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

Keywords: acute stroke; alteplase; ischemic stroke; network meta-analysis; tenecteplase.

Publication types

Systematic Review

Grants and funding

This study was supported by National Natural Science Foundation of China (82260243), National Key R&D Program of China (No.2018YFC1311305), and Guangxi Zhuang Autonomous Region Health Commission self-funded project (Z-A20220024).