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SGLT-2 inhibitors: more evidence of cardiovascular benefit in heart failure

By Nicole MacKee
Sodium­-glucose cotransporter­-2 (SGLT­-2) inhibitors can play a key role in reducing hospitalisation and death from heart failure, regardless of patients’ diabetes status, say experts after a second trial has found benefit with an SGLT­-2 drug.

In the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR­-Reduced), 3730 patients with heart failure (class II, III or IV) and an ejection fraction of 40% or less were assigned to either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy.

After a median follow up of 16 months, the researchers found a 25% reduced risk of heart failure death or hospitalisation in patients in the empagliflozin group (hazard ratio [HR], 0.75). The beneficial effects were reported regardless of patients’ diabetes status.

Writing in The New England Journal of Medicine, the researchers said the benefit was primarily related to a 31% lower risk of hospitalisation for heart failure.

The industry­-funded trial also found that empagliflozin­-treated patients had lower risks of renal outcomes, although they did have a higher rate of uncomplicated genital tract infection.

These latest findings come after the publication in 2019 of The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA­HF) trial that found that dapagliflozin, another SGLT­-2 inhibitor, was effective in reducing the risk of cardiovascular death or worsening heart failure when compared with placebo (HR, 0.74).

Professor Stephen Nicholls, Director of MonashHeart and the Victorian Heart Institute, Melbourne, said the EMPEROR­ Reduced trial findings were ‘good news for patients’.

‘We now have two large outcomes trials that demonstrate that use of SGLT­2 inhibitors have a cardiovascular benefit in patients with heart failure and reduced ejection fractions regardless of diabetes status,’ he said. ‘This is very good for these patients as it demonstrates another class of agents that are beneficial for patients with heart failure with reduced ejection fraction.’

The author of an editorial accompanying the trial noted that the Canadian Cardiovascular Society and the Canadian Heart Failure Society had recommended the use of SGLT­-2 inhibitors in patients with mild or moderate heart failure who have an ejection fraction of 40% or less.

Professor Nicholls said Australia was moving in a similar direction.

‘Heart failure with reduced ejection fraction is under consideration from a labelling perspective,’ he said. ‘In parallel, it will be important for guideline committees to determine how best to integrate SGLT­-2 inhibitors into treatment algorithms for clinical use.’
N Engl J Med 2020; doi: 10.1056/NEJMoa2022190.
N Engl J Med 2020; doi 10.1056/NEJMe2027915.