Chronic Metformin Treatment is Associated with Reduced Myocardial Infarct Size in Diabetic Patients with ST-segment Elevation Myocardial Infarction

Lexis, Chris P. H.; Wieringa, Wouter G.; Hiemstra, Bart; Deursen, Vincent M. van; Lipšic, Erik; Harst, Pim van der; Veldhuisen, Dirk J. van; Horst, Iwan C. C. van der

doi:10.1007/s10557-013-6504-7

Cited by 50 publications

(54 citation statements)

References 36 publications

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“…Recent animal studies [12,14,21] have demonstrated a cardioprotective effect of metformin in non-diabetic rats subjected to coronary ligation. An observational human study suggested reduction in infarct size in patients with diabetes on metformin therapy undergoing PCI for STEMI [22]. All this information formed the basis of a recently reported study designed to look at the LVEF in non-diabetic patients with STEMI undergoing PCI treated with metformin [16].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction

Abualsuod

Rutland

Watts

et al. 2015

Cardiovasc Drugs Ther

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Section: Discussionmentioning

confidence: 99%

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction

Abualsuod

Rutland

Watts

et al. 2015

Cardiovasc Drugs Ther

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“…Previous clinical study reported that metformin did not improve LVEF in ST-elevated MI (STEMI) nondiabetic patients (Lexis et al 2014a). However, metformin improved clinical outcomes in metabolic syndrome patients undergoing percutaneous coronary intervention ) and reduced MI size in diabetic patients with STEMI (Lexis et al 2014b). Furthermore, metformin has been shown to improve cardiac function in normal rats with chronic MI (Soraya et al 2012(Soraya et al , 2014.…”

Section: Figurementioning

confidence: 98%

Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction

Apaijai

Inthachai

Lekawanvijit

et al. 2016

Journal of Endocrinology

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Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or highfat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10 mg/kg/day), metformin (30 mg/kg/day), DPP4 inhibitor vildagliptin (3 mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-β expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling.

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“…In humans, a recent retrospective cohort study sought to investigate the association between metformin use and MI size in patients presenting with an acute MI 10. The researchers divided patients with diabetes into metformin versus nonmetformin groups and estimated MI size using peak values of serum creatine kinase, CKMB, and troponin T 10.…”

Section: Discussionmentioning

confidence: 99%

“…In a 2013 retrospective analysis, Zhao et al found that chronic pretreatment with metformin was associated with the reduction of the no‐reflow phenomenon in patients with diabetes mellitus after primary angioplasty for acute MI 9. In a 2014 retrospective cohort study, Lexis et al sought to investigate the association between metformin use and MI size in patients presenting with an acute MI 10. The researchers found that the use of metformin treatment was an independent predictor of smaller MI size 10.…”

Section: Introductionmentioning

confidence: 99%

Metformin and Myocardial Injury in Patients With Diabetes and ST‐Segment Elevation Myocardial Infarction: A Propensity Score Matched Analysis

Basnet

Kozikowski

Makaryus

et al. 2015

JAHA

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BackgroundAlthough animal studies have documented metformin's cardioprotective effects, the impact in humans remains elusive. The study objective was to explore the association between metformin and myocardial infarct size in patients with diabetes presenting with ST‐segment elevation myocardial infarction.Methods and ResultsData extraction used the National Cardiovascular Data CathPCI Registry in all patients with diabetes aged >18 years presenting with ST‐segment elevation myocardial infarction at 2 academic medical centers from January 2010 to December 2013. The exposure of interest was ongoing metformin use before the event. Propensity score matching was used for the metformin and nonmetformin groups on key prognostic variables. All matched pairs had acceptable D scores of <10%, confirming an efficient matching procedure. The primary outcome was myocardial infarct size, reflected by peak serum creatine kinase–myocardial band, troponin T, and hospital discharge left ventricular ejection fraction. Of all 1726 ST‐segment elevation myocardial infarction cases reviewed, 493 patients had diabetes (28.5%), with 208 metformin users (42.1%) and 285 nonusers. Matched pairs analysis yielded 137 cases per group. The difference between metformin and nonmetformin groups was −18.1 ng/mL (95% CI −55.0 to 18.8; P=0.56) for total peak serum creatine kinase–myocardial band and −1.1 ng/mL (95% CI −2.8 to 0.5; P=0.41) for troponin T. Median discharge left ventricular ejection fraction in both groups was 45, and the difference between metformin and nonmetformin users was 0.7% (95% CI −2.2 to 3.6; P=0.99).ConclusionsNo statistically significant association of cardioprotection was found between metformin and myocardial infarct size in patients with diabetes and acute ST‐segment elevation myocardial infarction.

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Chronic Metformin Treatment is Associated with Reduced Myocardial Infarct Size in Diabetic Patients with ST-segment Elevation Myocardial Infarction

Abstract: Chronic metformin treatment is associated with reduced MI size compared to non-metformin based strategies in diabetic patients presenting with STEMI. Metformin might have additional beneficial effects beyond glucose lowering efficacy.

Cited by 50 publications

References 36 publications

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction

Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction

Metformin and Myocardial Injury in Patients With Diabetes and ST‐Segment Elevation Myocardial Infarction: A Propensity Score Matched Analysis

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