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

Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08). Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.