Association of metformin with the mortality and incidence of cardiovascular events in patients with pre-existing cardiovascular diseases

Background and Purpose Whereas whether metformin reduce all-cause, cardiovascular mortality, and incidence of cardiovascular events in patients with cardiac diseases remains inconclusive. Experimental Approach PubMed and Embase were searched up to May 2020 with a registration in PROSPERO (CRD42020189905) were collected. This article includes randomized controlled trials (RCT) and cohort studies. Hazard ratio (HR) with 95% CI was pooled across various trials by a random-effects model. Risk of bias was accounted as per Cochrane and Newcastle-Ottawa Scale (NOS) guidelines. Key Results This article enrolled 48 articles (1999-2020) for qualitative synthesis and identified 26 articles (33 studies in total, 61,704 patients) for final quantitative synthesis. Compared with non-metformin control, metformin is associated with reduced all-cause mortality (HR: 0.90; 95% CI: 0.83, 0.98; P = 0.01), cardiovascular mortality (HR: 0.89; 95% CI: 0.85, 0.94; P < 0.0001), incidence of coronary revascularization (HR: 0.79; 95% CI: 0.64, 0.98; P = 0.03), and heart failure (HR: 0.90; 95% CI: 0.87, 0.94; P < 0.0001) in patients with cardiac diseases, whereas metformin is not associated with reduced incidence of myocardial infarction (HR: 0.97; 95% CI: 0.80, 1.17; P = 0.73), angina (HR: 0.29; 95% CI: 0.04, 2.35; P = 0.25), and stroke (HR: 0.95; 95% CI: 0.78, 1.16; P = 0.59). Conclusion and Implications Metformin reduces all-cause mortality, cardiovascular mortality, incidence of coronary revascularization, and heart failure of patients with cardiac diseases, whereas metformin is not associated with reduced incidence of myocardial infarction, angina, and stroke.