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Original research
Who may benefit from lower dosages of intravenous tissue plasminogen activator? Results from a cluster data analysis
  1. Yi Dong1,
  2. Ye Han2,
  3. Haipeng Shen3,
  4. Yilong Wang4,
  5. Frank Ma5,
  6. Hao Li6,
  7. Yongjun Wang4,
  8. Qiang Dong1
  1. 1 Department of Neurology, Huashan Hospital Fudan University, Shanghai, Shanghai, China
  2. 2 Department of Business Administration, College of Business, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA
  3. 3 Faculty of Business and Economics, University of Hong Kong, Hong Kong, China
  4. 4 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  5. 5 Medical Research Center, DotHealth, Shanghai, China
  6. 6 Big data and AI dempartment, China National Clinical Research Center for Neurological Diseases, Beijing, China
  1. Correspondence to Dr Qiang Dong; dong_qiang{at}fudan.edu.cn; Dr Yilong Wang; yilong528{at}aliyun.com

Abstract

Background The risk of symptomatic intracranial haemorrhage (sICH) after thrombolysis is low but severe. Lower dose of alteplase may reduce the risk of sICH. We aim to identify subsets of patients who could benefit from lower dose of alteplase compared with standard dose.

Methods Data from two observational registries were pooled together. A total of 3479 patients who had acute ischaemic stroke were entered into the interaction tree model. The response variable was the rate of sICH per the definition of the National Institute of Neurological Disorders and Stroke Study. Clinical improvement was measured by the National Institutes of Health Stroke Scale (NIHSS) and defined as NIHSS 0 or 1 or an improvement of more than 4 points (within 7 days or at discharge). Rare event logistic regression was performed to analyse the OR of safety outcome.

Results To optimise the interaction effect between tissue plasminogen activator (tPA) dosage (standard/lower) and patient subgroups, three subgroups based on the severity of stroke were identified: (1) NIHSS ≤4, (2) NIHSS between 5 and 14, and (3) NIHSS ≥15. The estimated difference of OR of having sICH was 2.71 (95% CI 0.80 to 7.69, p=0.10) for mild, 0.13 (95% CI 0.02 to 0.68, p=0.01) for moderate, and 0.65 (95% CI 0.19 to 2.55, p=0.52) for severe, respectively. In addition, patients who had moderate stroke treated with lower dose had comparable efficacy outcome (OR 1.23, 95% CI 0.71 to 2.13, p=0.45).

Conclusion Our analysis demonstrated that in patients who had moderate stroke, lower doses of alteplase are associated with significant sICH reduction and non-inferior performance in efficacy, compared with those in the standard dose group.

Trial registration number The TIMS-China was a national prospective stroke registry on thrombolytic therapy using intravenous tPA in patients who had acute ischaemic stroke. The results were initially published in 2012 without a clinical trial registration number. The Shanghai Stroke Service System was registered at www.clinicaltrial.gov (NCT02735226).

  • stroke
  • thrombolysis
http://creativecommons.org/licenses/by-nc/4.0/

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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/svn-2020-000388

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    Footnotes

    • YD and YH are joint first authors.

    • YLW and QD contributed equally.

    • Correction notice The paper has been updated since first published to update affiliations of Dr Yilong Wang, first authorship, and funding details.

    • Contributors QD and YLW designed this study. YD and YH performed the analysis. HS, FM and HL supervised the analysis. YD drafted the manuscript. YJW and QD provided revisions.

    • Funding The Ministry of Science and Technology Major Project of China (2017YFC1310903), University of Hong Kong BRC Grant, and Patrick SC Poon Professorship Endowment Fund.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study is a data-driven post-hoc analysis. The original ethics approval has been approved by the Tiantan Hospital and studies have been reported.

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

    • Data availability statement Data are available upon reasonable request to QD at dong_qiang@fudan.edu.cn or YLW at yilong528@aliyun.com. Data from this study for data validation and academic corporations have now been made publicly available through direct requests from both these study principal investigators.