Sodium-glucose co-transporter 2 inhibitors for HFrEF

The sodium-glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin reduce cardiovascular mortality and hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), with or without type 2 diabetes. These outcomes have been studied in 2 large, randomised placebo-controlled trials, in which dapagliflozin or empagliflozin were added to standard care in patients with established HFrEFMcMurray, 2019Packer, 2020. While these outcomes in patients with HFrEF may be a class effect, at the time of writing, the evidence is strongest for dapagliflozin and empagliflozin.

The mechanism by which SGLT2 inhibitors improve HFrEF outcomes is unclear; beneficial effects on cardiac remodelling have been reported in some studies. Several possible mechanisms include favourable effects on haemodynamics and cellular energetics, decreased tissue sodium concentrations, improved vascular function and enhanced erythropoiesisRasalam, 2021.

Start an SGLT2 inhibitor (along with a renin-angiotensin system inhibitor, beta blocker and mineralocorticoid receptor antagonist) at diagnosis or within 2 to 4 weeks of diagnosis of HFrEF; see Starting drug therapy for HFrEF. For patients previously diagnosed with HFrEF, add an SGLT2 inhibitor to therapy. Use:

SGLT2 inhibitors have a natriuretic effect; if the patient is taking a loop diuretic, consider reducing the dose of the loop diuretic when starting an SGLT2 inhibitor if the patient is euvolaemic.

SGLT2 inhibitors have been associated with ketoacidosis (with or without accompanying hyperglycaemia). This risk is higher if the patient has a severe intercurrent illness or infection, has undergone bowel preparation or surgery, has restricted oral intake, or is dehydrated. Advise patients to withhold the SGLT2 inhibitor when they have restricted oral intake, and inform them of when to seek medical attention—see Diabetic ketoacidosis associated with SGLT2 inhibitors for more information.

A small reduction in estimated glomerular filtration rate (eGFR) is common when an SGLT2 inhibitor is started; however, these drugs have a favourable long-term effect on kidney function.