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

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.

SUBMITTER: Hesen NA

PROVIDER: S-EPMC5568412 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Hesen Nienke A NA Riksen Niels P NP Aalders Bart B Brouwer Michelle AE MA Ritskes-Hoitinga Merel M El Messaoudi Saloua S El Messaoudi Saloua S Wever Kimberley E KE

PloS one 20170823 8

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 ...[more]

PMID: 28832637

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Project description:BackgroundA comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking.ObjectiveTo summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI.MethodsArticles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020.Results15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction).ConclusionsOur findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.

Project description:BACKGROUND:The effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies. We aimed to systematically review studies reporting on the associations between AP drug use and stroke or MI risk, and to investigate whether associations differed among different sub-populations. METHODS:We searched Medline, EMBASE, PsychINFO and Cochrane Library (from inception to May 28, 2017) for observational studies reporting on AP drug use and MI or stroke occurrence. We performed random-effects meta-analyses for each outcome, performing sub-groups analyses by study population - specifically general population (i.e. those not restricted to patients with a particular indication for AP drug use), people with dementia only and psychiatric illness only. Where feasible we performed subgroup analyses by AP drug class. RESULTS:From 7008 articles, we included 29 relevant observational studies, 19 on stroke and 10 on MI. Results of cohort studies that included a general population indicated a more than two-fold increased risk of stroke, albeit with substantial heterogeneity (pooled HR 2.31, 95% CI 1.13, 4.74, I2 = 83.2%). However, the risk among patients with dementia was much lower, with no heterogeneity (pooled HR 1.16, 95% CI 1.00, 1.33, I2 = 0%) and there was no clear association among studies of psychiatric populations (pooled HR 1.44, 95% CI 0.90, 2.30; substantial heterogeneity [I2 = 78.8])). Associations generally persisted when stratifying by AP class, but few studies reported on first generation AP drugs. We found no association between AP drug use and MI risk (pooled HR for cohort studies: 1.29, 95% CI 0.88, 1.90 and case-control studies: 1.07, 95% CI 0.94, 1.23), but substantial methodological and statistical heterogeneity among a relatively small number of studies limits firm conclusions. CONCLUSIONS:AP drug use may be associated with an increased risk of stroke, but there is no clear evidence that this risk is further elevated in patients with dementia. Further studies are need to clarify the effect of AP drug use on MI and stroke risk in different sub-populations and should control for confounding by indication and stratify by AP drug class.

Project description:IntroductionST-segment elevation myocardial infarction (STEMI) is the most severe clinical form of acute myocardial infarction, for which the current treatment consists of effective and timely myocardial reperfusion (within 12 hours of symptom onset). However, between 10% and 15% of patients with STEMI arrive at hospital facilities 12 hours after the onset of symptoms (late presentation). Therefore, the objective of the present study will be to determine if late revascularisation (12-72 hours after the onset of symptoms) affects the indicators of cardiovascular mortality, reinfarction, recurrent infarction, hospitalisation for heart failure and post infarction angina compared with no late revascularisation in patients with STEMI.Methods and analysisA systematic literature search of PubMed, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Scopus and Global Health will be conducted. Publications in English, Portuguese or Spanish that report the clinical results of primary percutaneous revascularisation (primary PCI) in adult patients with STEMI 12-72 hours after the onset of symptoms will be included. Studies with participants with a diagnosis other than STEMI or patients with STEMI of >12 hours complicated by heart failure, cardiogenic shock or ventricular arrhythmias, and studies of combined interventions (pharmacoinvasive strategy) were excluded. Two independent authors will identify the relevant publications, and discrepancies will be adjudicated by a third author. Data extraction will be performed by two independent authors and verified by a third author. Risk of bias of studies will be assessed using the Cochrane 'risk of bias' tool (RoB 2) or Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. If appropriate, a meta-analysis will be performed in order to examine the effect of late revascularisation in clinical outcomes of interest.Ethics and discussionThis study will use published data only, thus, ethical approval will not be required. The results will be disseminated through peer-reviewed publication and conference presentations.Prospero registration numberCRD42021283429.

Project description:BACKGROUND:Myocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mainly the result of the interplay of genetic and environmental risk factors. The regulation of thrombosis, inflammation and cholesterol and lipid metabolism are the main factors that have been proposed thus far to be involved in the pathogenesis of MI. Traditional risk-estimation tools depend largely on conventional risk factors but there is a need for identification of novel biochemical and genetic markers. The aim of the study is to identify differentially expressed genes that are consistently associated with the incidence myocardial infarction (MI), which could be potentially incorporated into the traditional cardiovascular diseases risk factors models. METHODS:The biomedical literature and gene expression databases, PubMed and GEO, respectively, were searched following the PRISMA guidelines. The key inclusion criteria were gene expression data derived from case-control studies on MI patients from blood samples. Gene expression datasets regarding the effect of medicinal drugs on MI were excluded. The t-test was applied to gene expression data from case-control studies in MI patients. RESULTS:A total of 162 articles and 174 gene expression datasets were retrieved. Of those a total of 4 gene expression datasets met the inclusion criteria, which contained data on 31,180 loci in 93 MI patients and 89 healthy individuals. Collectively, 626 differentially expressed genes were detected in MI patients as compared to non-affected individuals at an FDR q-value?=?0.01. Of those, 88 genes/gene products were interconnected in an interaction network. Totally, 15 genes were identified as hubs of the network. CONCLUSIONS:Functional enrichment analyses revealed that the DEGs and that they are mainly involved in inflammatory/wound healing, RNA processing/transport mechanisms and a yet not fully characterized pathway implicated in RNA transport and nuclear pore proteins. The overlap between the DEGs identified in this study and the genes identified through genetic-association studies is minimal. These data could be useful in future studies on the molecular mechanisms of MI as well as diagnostic and prognostic markers.

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

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

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