RT Journal Article SR Electronic T1 Cardiovascular safety of metformin and sulfonylureas in patients with different cardiac risk profiles JF Heart JO Heart FD BMJ Publishing Group Ltd and British Cardiovascular Society SP 1544 OP 1551 DO 10.1136/heartjnl-2015-308711 VO 102 IS 19 A1 Raphael Wurm A1 Michael Resl A1 Stephanie Neuhold A1 Rudolf Prager A1 Helmut Brath A1 Claudia Francesconi A1 Greisa Vila A1 Guido Strunk A1 Martin Clodi A1 Anton Luger A1 Richard Pacher A1 Martin Hülsmann YR 2016 UL http://heart.bmj.com/content/102/19/1544.abstract AB Objectives/Background Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels.Methods 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis.Results During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP.Conclusions Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.