IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0183664.html
   My bibliography  Save this article

A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction

Author

Listed:
  • Nienke A Hesen
  • Niels P Riksen
  • Bart Aalders
  • Merel Ritskes-Hoitinga
  • Saloua El Messaoudi
  • Kimberley E Wever

Abstract

Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE’s risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.

Suggested Citation

  • Nienke A Hesen & Niels P Riksen & Bart Aalders & Merel Ritskes-Hoitinga & Saloua El Messaoudi & Kimberley E Wever, 2017. "A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-18, August.
    • Handle: RePEc:plo:pone00:0183664
    DOI: 10.1371/journal.pone.0183664
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183664
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183664&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0183664?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kimberley E Wever & Theo P Menting & Maroeska Rovers & J Adam van der Vliet & Gerard A Rongen & Rosalinde Masereeuw & Merel Ritskes-Hoitinga & Carlijn R Hooijmans & Michiel Warlé, 2012. "Ischemic Preconditioning in the Animal Kidney, a Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-10, February.
    2. Simone J Jonker & Theo P Menting & Michiel C Warlé & Merel Ritskes-Hoitinga & Kimberley E Wever, 2016. "Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-19, March.
    3. Kimberley E Wever & Carlijn R Hooijmans & Niels P Riksen & Thomas B Sterenborg & Emily S Sena & Merel Ritskes-Hoitinga & Michiel C Warlé, 2015. "Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-17, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kimberley E Wever & Carlijn R Hooijmans & Niels P Riksen & Thomas B Sterenborg & Emily S Sena & Merel Ritskes-Hoitinga & Michiel C Warlé, 2015. "Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-17, November.
    2. Simone J Jonker & Theo P Menting & Michiel C Warlé & Merel Ritskes-Hoitinga & Kimberley E Wever, 2016. "Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-19, March.
    3. Kimberley E Wever & Moira H D Bruintjes & Michiel C Warlé & Carlijn R Hooijmans, 2016. "Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-25, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0183664. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.