Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke

Hanna M Vesterinen, Gillian L Currie, Samantha Carter, Sarah Mee, Ralf Watzlawick, Kieren J Egan, Malcolm R Macleod, Emily S Sena

Research output: Contribution to journalReview article

28 Citations (Scopus)
6 Downloads (Pure)

Abstract

There is currently only one clinically approved drug, tissue plasminogen activator (tPA), for the treatment of acute ischaemic stroke. The RhoA pathway, including RhoA and its downstream effector Rho kinase (ROCK), has been identified as a possible therapeutic target. Our aim was to assess the impact of study design characteristics and study quality on reported measures of efficacy and to assess for the presence and impact of publication bias. We conducted a systematic review and meta-analysis on publications describing the efficacy of RhoA and ROCK inhibitors in animal models of focal cerebral ischaemia where outcome was assessed as a change in lesion size or neurobehavioural score, or both. We identified 25 published papers which met our inclusion criteria. RhoA and ROCK inhibitors reduced lesion size by 37.3% in models of focal cerebral ischaemia (95% CI, 28.6% to 46.0%, 41 comparisons), and reduced neurobehavioural data by 40.5% (33.4% to 47.7%, 30 comparisons). Overall study quality was low (median=4, interquartile range 3-5) and measures to reduce bias were seldom reported. Publication bias was prevalent and associated with a substantial overstatement of efficacy for lesion size. RhoA and ROCK inhibitors appear to be effective in animal models of stroke. However the low quality score, publication bias and limited number of studies are areas which need attention prior to conducting clinical trials.

Original languageEnglish
Number of pages9
JournalSystematic Reviews
Volume2
DOIs
Publication statusPublished - 20 May 2013

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Publication Bias
rho-Associated Kinases
Meta-Analysis
Animal Models
Stroke
Brain Ischemia
Tissue Plasminogen Activator
Publications
Clinical Trials
Pharmaceutical Preparations
Therapeutics

Keywords

  • meta-analysis
  • ischaemic stroke
  • ROCK inhibitors
  • RhoA inhibitors
  • publication bias
  • study quality
  • systematic review
  • animal studies

Cite this

Vesterinen, Hanna M ; Currie, Gillian L ; Carter, Samantha ; Mee, Sarah ; Watzlawick, Ralf ; Egan, Kieren J ; Macleod, Malcolm R ; Sena, Emily S. / Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke. In: Systematic Reviews. 2013 ; Vol. 2.
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Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke. / Vesterinen, Hanna M; Currie, Gillian L; Carter, Samantha; Mee, Sarah; Watzlawick, Ralf; Egan, Kieren J; Macleod, Malcolm R; Sena, Emily S.

In: Systematic Reviews, Vol. 2, 20.05.2013.

Research output: Contribution to journalReview article

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AU - Mee, Sarah

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AU - Macleod, Malcolm R

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