Research in brief: Empagliflozin for patients with heart failure and preserved ejection fraction

of Anker SD, Butler J, Filippatos G et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021;385:1451–61. Heart failure with preserved ejection fraction (HFpEF) is a term used to describe patients with clinical ‘symptoms and signs of heart failure with [a left ventricular ejection fraction (LVEF)] ≥50%’ and is thought to encompass about 50% of all heart failure patients. In common with heart failure with reduced ejection fraction (HFrEF), it is associated with significant morbidity and mortality, but in contrast, no treatment has been shown to improve prognosis for HFpEF. Recent randomised controlled trials have provided an evidence base for sodium-dependent glucose cotransporter-2 (SLGT2) inhibitors as prognostic medications for patients in HFrEF. Previously thought to reduce heart failure-related hospitalisation and adverse renal events in patients solely with type 2 diabetes, further trials have shown SGLT2 inhibitors to improve outcomes in heart failure regardless of diabetes status. The mechanism by which SGLT2 inhibitors provide cardiorenal benefit remains unclear. The anti-hyperglycaemic actions of SGLT2 inhibitors cannot fully explain their mechanism given that other antidiabetic medications have greater hypoglycaemic effects without an impact on heart failure prognosis. Proposed mechanisms of actions include reduction in sodium and water retention in the proximal renal tubule leading to improving renal function, which in turn may reduce afferent sympathetic supply to the heart and reduce cardiac inflammation. While the benefits of SGLT2 inhibitors in HFrEF are now established and in nascent treatment guidelines, their role in managing patients with HFpEF is unclear. In this summary, we