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Review
Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke: an updated systematic review
  1. Xia Wang1,2,
  2. Shoujiang You3,
  3. Shoichiro Sato4,
  4. Jie Yang5,
  5. Cheryl Carcel1,2,6,
  6. Danni Zheng1,2,
  7. Sohei Yoshimura1,2,4,
  8. Craig S Anderson1,2,6,7,
  9. Else Charlotte Sandset8,
  10. Thompson Robinson9,
  11. John Chalmers1,2,3,
  12. Vijay K Sharma10,11
  1. 1 The George Institute for Global Health, Newtown, New South Wales, Australia
  2. 2 Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
  3. 3 Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China
  4. 4 Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
  5. 5 Department of Neurology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
  6. 6 Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  7. 7 The George Institute China, Peking University Health Science Center, Beijing, China
  8. 8 Department of Neurology, Oslo University Hospital, Oslo, Norway
  9. 9 Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases, University of Leicester, Leicester, UK
  10. 10 Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  11. 11 Division of Neurology, National University Hospital, Singapore
  1. Correspondence to Dr Jie Yang; yangjie1126{at}163.com

Abstract

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2–6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH.

  • acute ischemic stroke
  • Asian
  • low-dose tissue plasminogen activator
  • thrombolysis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/svn-2017-000112

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    Footnotes

    • Contributors XW, VKS and JC conceived the study. XW, SY and DZ were involved in the article screening process and data extraction. All authors were involved in drafting of the manuscript and in critically reviewing and revising it. All authors provided final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately addressed.

    • Funding The work was supported by grants from the National Natural Science Foundation of China (81471199) and the Department of Science and Technology of Jiangsu Province (BK20161113).

    • Competing interests TR is a National Institute for Health Research Senior Investigator, and reports receiving speaking fees from Bayer and Boehringer Ingelheim, and fees for Advisory Panels from Bayer and Daiichi Sankyo. CSA reports receiving fees for Advisory Panels of AstraZeneca and Medtronic, speaking at seminars for Takeda China and Boehringer Ingelheim, and a research grant from Takeda China. JC reports research grants and lecture fees from Servier for the ADVANCE trial and post-trial follow-up.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.