• Yasuaki Nakagawa and Koichiro Kuwahara.
• Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
• J Cardiol. 2020 Aug 1; 76 (2): 123-131.

AbstractDespite recent developments in various therapies, heart failure remains a leading cause of morbidity and mortality worldwide. New pharmacological approaches are therefore needed to improve the outcomes of patients with heart failure. Diabetes mellitus is an important risk factor for heart failure, but until recently there had been no evidence that hypoglycemic agents prevent heart failure. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have now been shown to prevent cardiovascular events, especially hospitalization for heart failure, in three large randomized clinical trials: EMPA-REG OUTCOME, the CANVAS program, and the DECLARE-TIMI58 trial. It is expected, therefore, that SGLT2 inhibitors will be useful therapeutic agents for the treatment of heart failure. The DAPA-HF trial recently demonstrated that dapagliflozin significantly reduces cardiovascular death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF). Importantly, these benefits of dapagliflozin were similarly observed in patients with or without diabetes, suggesting the drug's efficacy is independent of glycemic reduction. The results of that study highlight the significance of SGLT2 inhibition as a novel therapeutic approach to treating HFrEF, irrespective of the presence or absence of diabetes. Findings of the DAPA-HF trial may also challenge current assumptions about the mechanisms underlying the cardioprotective action of SGLT2 inhibitors. It is anticipated that ongoing clinical trials, mainly using dapagliflozin and empagliflozin, will provide further insight into the clinical importance of these drugs for the treatment of heart failure, including heart failure with preserved ejection fraction (HFpEF), and also the mechanisms underlying those clinical benefits.Copyright © 2020. Published by Elsevier Ltd.

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