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Research paper
Statins and the risk of intracerebral haemorrhage inpatients withstroke:systematic review and meta-analysis
  1. Oliver Jonathan Ziff1,2,
  2. Gargi Banerjee1,
  3. Gareth Ambler3,
  4. David J Werring1,2
  1. 1 Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL, London, UK
  2. 2 The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
  3. 3 Department of Statistical Science, UCL, London, UK
  1. Correspondence to Dr David J Werring, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London WC1N 3BG, UK; d.werring{at}ucl.ac.uk

Abstract

Objective Whether statins increase the risk of intracerebral haemorrhage (ICH) in patients with a previous stroke remains uncertain. This study addresses the evidence of statin therapy on ICH and other clinical outcomes in patients with previous ischaemic stroke (IS) or ICH.

Methods A systematic literature review and meta-analysis was performed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess observational and randomised studies comparing statin therapy with control (placebo or no treatment) in patients with a previous ICH or IS. The risk ratios (RR) for the primary outcome (ICH) and secondary outcomes (IS, any stroke, mortality and function) were pooled using random effects meta-analysis according to stroke subtype.

Results Forty-three studies with a combined total of 317 291 patient-years of follow-up were included. In patients with previous ICH, statins had no significant impact on the pooled RR for recurrent ICH (1.04, 95% CI 0.86 to 1.25; n=23 695); however, statins were associated with significant reductions in mortality (RR 0.49, 95% CI 0.36 to 0.67; n=89 976) and poor functional outcome (RR 0.71, 95% CI 0.67 to 0.75; n=9113). In patients with previous IS, statins were associated with a non-significant increase in ICH (RR 1.36, 95% CI 0.96 to 1.91; n=103 525), but significantly lower risks of recurrent IS (RR 0.74, 95% CI 0.66 to 0.83; n=53 162), any stroke (RR 0.82, 95% CI 0.67 to 0.99; n=55 260), mortality (RR 0.68, 95% CI 0.50 to 0.92; n=74 648) and poor functional outcome (RR 0.83, 95% CI 0.76 to 0.91; n=34 700).

Conclusions Irrespective of stroke subtype, there were non-significant trends towards future ICH with statins. However, this risk was overshadowed by substantial and significant improvements in mortality and functional outcome among statin users.

Trial registration number CRD42017079863.

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Footnotes

  • Contributor OJZ developed the eligibility criteria, performed the primary literature search, contributed to data extraction and drafting of the manuscript. GB contributed to data extraction and critical revision of the manuscript. GA contributed to statistical analysis and critical revision of the manuscript. DJW designed the study concept, led the study group and critically revised the manuscript.

  • Funding This work was undertaken at the University College London Hospitals NHS Foundation Trust/University College London who received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. OJZis funded by the National Institute of Health Research UK. GBreceived research support from the Rosetrees Trust. DJW receives research funding support from the British Heart Foundation and the Stroke Association (TSA BHF 2009/01; TSA PPA 2015/04; BHF CS/17/6/33361).

  • Competing interests OJZ, GB and GA have no relevant conflicts. DJW was UK chief investigator for A9951024 (Pfizer) and has received consultancy and lecture fees from Bayer.

  • Patient consent Not required.

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

  • Data sharing statement No additional data are available.

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