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

Abstract

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.

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

“…In one study, while patients with acute st-segment elevation patients (STEMI) were treated with metformin for 4 months, metformin was not found to increase ejection fraction (53.1% vs 54.8%, P = 0.1) or decrease n-terminal pro-brain natriuretic peptide (nt-probnp) levels (167 vs. 167 ng/L, P = 0.66) [39]. Another STEMI study also found no improvement in ejection fraction in diabetic patients treated with metformin and a 0.7% difference between those taking metformin and those not taking metformin [23]. After it was shown it could reduce mortality, metformin was further analyzed in this meta-analysis for its effect on cardiac function: LVEF, CK-MB and BNP were specifically analyzed.…”

Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

“…However, a recently published pre-clinical study of post-conditioning with metformin in pigs found no difference in infarct size or LV function compared to vehicle [32]. Human studies have used biomarkers as a surrogate of infarct size in the context of STEMI [16, 17]. A study of 660 diabetic patients with STEMI showed a reduction of infarct size (according to serum biomarkers) in the metformin group, although the comparator group were treated with diet alone, which may have exaggerated the effect [16].…”

“…A study of 660 diabetic patients with STEMI showed a reduction of infarct size (according to serum biomarkers) in the metformin group, although the comparator group were treated with diet alone, which may have exaggerated the effect [16]. A propensity score matched analysis of 493 diabetic patients with STEMI showed no association between metformin and infarct size or LV function, although no information on drug treatment of diabetes in the control group was provided [17]. In an analogous, randomized trial of oral metformin, started after primary percutaneous coronary intervention for STEMI in patients without diabetes, no benefit was seen on LV function, MACE, all-cause mortality, or new-onset diabetes [33, 34].…”

“…It has been hypothesized that the favorable effects of pre-treatment with metformin in patients with AMI relate to cardioprotection against IRI, independent of its hypoglycaemic actions [14]. However, to our knowledge, no studies have investigated outcomes after AMI in diabetic patients pre-treated with metformin, with the exception of mixed results from studies investigating the association between metformin treatment prior to ST-segment elevation AMI (STEMI) and infarct size (defined using serum biomarkers as surrogate measures) and left ventricular (LV) function [16, 17]. A mortality benefit of pre-treatment with metformin has not been demonstrated in patients with AMI and, using linked electronic health records from the CALIBER resource, which prospectively records medication status, we investigated whether metformin administration is associated with cardioprotection to these patients.…”

Co‐morbidities and co‐medications as confounders of cardioprotection—Does it matter in the clinical setting?

“…In a retrospective study, chronic metformin treatment of diabetic patients prior to STEMI was associated with reduced biomarker release (Lexis et al, 2014). However, another retrospective study did not confirm such benefit (Basnet et al, 2015). The acute effect of metformin on ischaemia/reperfusion injury has not been clarified in a clinical setting.…”