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Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies

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Abstract

Objective

Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke.

Methods

We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3 months, defined as a score of 0–1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality.

Results

Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months (odds ratio [OR], 1.10; 95% CI 0.98–1.23; risk difference [RD] 2.4%, 95% CI − 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (OR, 1.16; 95% credible interval 1.02–1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79–1.59; RD 0.3%, 95% CI − 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30–0.64; RD − 4.6%; 95% CI − 5.8 to − 2.9).

Conclusions

Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.

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Funding

This study is found by National Natural Science Foundation of China (Grant nos. 82274368 and 72204173), National Science Fund for Distinguished Young Scholars (Grant no. 82225049), Sichuan Provincial Central Government Guides Local Science and Technology Development Special Project (Grant no. 2022ZYD0127), and Fundamental Research Funds for the Central public welfare research institutes (Grant no. 2020YJSZX-3). JWB is supported, in part, by a CIHR Canada Research Chair in Prevention & Management of Chronic Pain.

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Authors and Affiliations

  1. Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China

    Yu Ma, Hunong Xiang, Minghong Yao, Xiaochao Luo, Fan Mei, Jiali Liu, Yuning Wang, Yanmei Liu, Kang Zou, Ling Li & Xin Sun

  2. NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China

    Yu Ma, Hunong Xiang, Minghong Yao, Xiaochao Luo, Fan Mei, Jiali Liu, Yuning Wang, Yanmei Liu, Kang Zou, Ling Li & Xin Sun

  3. Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China

    Yu Ma, Hunong Xiang, Minghong Yao, Xiaochao Luo, Fan Mei, Jiali Liu, Yuning Wang, Yanmei Liu, Kang Zou, Ling Li & Xin Sun

  4. Michael G. DeGroote National Pain Centre, McMaster University, Hamilton, ON, L8S 4K1, Canada

    Jason W. Busse

  5. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada

    Jason W. Busse

  6. Department of Anaesthesia, McMaster University, Hamilton, ON, L8S 4K1, Canada

    Jason W. Busse

  7. Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Jian Guo

  8. Evidence Based Social Science Research Centre, School of Public Health, Lanzhou University, Lanzhou, 730000, China

    Long Ge

  9. Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China

    Long Ge

  10. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China

    Bo Li & Wentao Li

  11. National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China

    Bo Li & Wentao Li

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  1. Yu Ma
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  2. Hunong Xiang
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  3. Jason W. Busse
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  7. Bo Li
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  15. Ling Li
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  16. Xin Sun
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Contributions

Yu Ma and Hunong Xiang contributed equally as co-first authors. Yu Ma and Hunong Xiang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Ling Li, Xin Sun, Yu Ma, Hunong Xiang, Jian Guo and Bo Li designed the study. Yu Ma, Hunong Xiang, Jason W. Busse, Ling Li and Xin Sun drafted the manuscript. Yu Ma, Hunong Xiang and Minghong Yao conducted the statistical analysis. Ling Li, Xin Sun, Jason W. Busse, Minghong Yao, and Long Ge gave administrative, technical, or material support. Xin Sun and Ling Li supervised the study. All authors analyzed and interpreted the data. All authors approved the critical revision of the manuscript for important intellectual content.

Corresponding authors

Correspondence to Ling Li or Xin Sun.

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Ma, Y., Xiang, H., Busse, J.W. et al. Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies. J Neurol 271, 2309–2323 (2024). https://doi.org/10.1007/s00415-024-12243-1

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