Tenecteplase versus alteplase for the treatment of acute ischemic stroke: a meta-analysis of randomized controlled trials

Abstract

Objectives

Tenecteplase, a modified variant of alteplase with greater fibrin specificity and longer plasma half-life, may have better efficacy and safety than alteplase in patients with acute ischemic stroke (AIS). We aimed to compare the benefits and risks of tenecteplase versus alteplase in the treatment of AIS.

Methods

Electronic databases were searched up to 10 February 2023 for randomized controlled trials evaluating the effect of tenecteplase versus alteplase in the treatment of AIS. The primary outcome was functional outcome at 90 days, and secondary outcomes including the symptomatic intracranial haemorrhage (SICH), and major neurological improvement. Subgroup analysis was performed based on the different dosage of tenecteplase.

Results

Ten studies with a total of 5123 patients were analysed in this meta-analysis. Overall, no significant difference between tenecteplase and alteplase was observed for functional outcome at 90 days (excellent: OR 1.08, 95%CI 0.93–1.26, I² = 26%; good: OR 1.04, 95%CI 0.83–1.30, I² = 56%; poor: OR 0.95, 95%CI 0.75–1.21, I² = 31%), SICH (OR 1.12, 95%CI 0.79–1.59, I² = 0%), and early major neurological improvement (OR 1.26, 95%CI 0.80–1.96, I² = 65%). The subgroup analysis suggested that the 0.25 mg/kg dose of tenecteplase had potentially greater efficacy and lower symptomatic intracerebral haemorrhage risk compared with 0.25 mg/kg dose tenecteplase.

Conclusions

Among AIS patients, there was no significant difference on clinical outcomes between tenecteplase and alteplase. Subgroup analysis demonstrated that 0.25 mg/kg doses of tenecteplase were more beneficial than 0.4 mg/kg doses of tenecteplase. Further studies are required to identify the optimal dosage of tenecteplase.

Key Messages

• Randomized controlled trials exploring comparative efficacy and safety of tenecteplase and alteplase have been yielding inconsistent results on various outcomes and merit the conduction of a meta-analysis to adequately answer these questions.

• Analysis of evidence from randomized studies suggests that tenecteplase is as safe as alteplase for the treatment of acute ischemic stroke and tenecteplase is potentially associated with more favourable outcomes.

• Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis.

Keywords:

• Tenecteplase
• alteplase
• stroke
• meta-analysis
• thrombolytic therapy

Acknowledgements

Registration: The protocol was preregistered in Open Science Framework (https://osf.io/y7whf).

Author contributions

Jian Huang conceived the idea, performed the analysis, and drafted the initial draft writing of this paper. Hui Zheng and Xianfeng Zhu contributed to the collection and interpretation of data. Kai Zhang provided technical support and helped to draft the work. Xiaofeng Ping contributed to the revision of this paper, and the final approval of the version to be published. All authors contributed to the article and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original contributions presented in the study are included in the article and Supplementary Material; further inquiries can be directed to the corresponding author.

Additional information

Funding

This work was supported in part by grants from the Hangzhou Bio-medicine and Health Industry Development Support Science and Technology Project (2022WJC076).