The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF) in context

The recently reported Dapagliflozin And Prevention of Adverse outcomes in Heart Failure trial (DAPA-HF) showed the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduced the risk of hospital admission for worsening heart failure, increased survival and improved symptoms in patients with heart failure with reduced ejection fraction (HFrEF).1–3 Although SGLT2 inhibitors had been developed as glucose-lowering treatments for patients with type 2 diabetes, approximately half the patients in DAPA-HF did not have type 2 diabetes.1–3 The benefits of dapagliflozin in DAPA-HF were of a similar magnitude in participants without diabetes to the benefits obtained in individuals with diabetes. Importantly, in both groups of patients, dapagliflozin in patients with HFrEF were observed when dapagliflozin was added to excellent background disease-modifying therapy for heart failure.

In this brief commentary, we wish to put these findings into perspective. There are two principal contextual considerations—how the patients randomized in DAPA-HF and their event rates compare with those in the prior SGLT2 inhibitor trials and, second, how the effects of dapagliflozin compare with those of other pharmacological treatments for HFrEF.