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2017 ; 12
(8
): e0183664
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A systematic review and meta-analysis of the protective effects of metformin in
experimental myocardial infarction
#MMPMID28832637
Hesen NA
; Riksen NP
; Aalders B
; Brouwer MA
; Ritskes-Hoitinga M
; El Messaoudi S
; Wever KE
PLoS One
2017[]; 12
(8
): e0183664
PMID28832637
show ga
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.
|Animals
[MESH]
|In Vitro Techniques
[MESH]
|Metformin/*therapeutic use
[MESH]
|Mice
[MESH]
|Myocardial Infarction/pathology/physiopathology/*prevention & control
[MESH]