Heart failure

SGLT2 inhibitor shows HF benefit regardless of ejection fraction

Heart failure patients with mildly reduced or preserved ejection fraction gain benefit from treatment with the SGLT2 inhibitor dapagliflozin, according to results from a major study presented at ESC 2022 meeting in Barcelona.

Findings from the DELIVER randomised controlled trial involving more than 6000 people with HF showed that dapagliflozin significantly reduced the primary composite endpoint of worsening heart failure or cardiovascular death by 18%, across the full spectrum of heart failure.

Study investigator Professor Scott Solomon of Brigham and Women’s Hospital, Harvard Medical School, Boston, said dapagliflozin had previously been shown to benefit patients with heart failure with reduced ejection fraction, but until it was less certain whether SGLT2 inhibitors were effective in patients with a higher left ventricular ejection fraction.

The DELIVER trial enrolled patients aged 40 years and above with symptomatic heart failure with an ejection fraction of greater than 40% who were either chronic outpatients, hospitalised or recently hospitalised, including patients who previously had an ejection fraction of 40% or below (i.e. heart failure with improved ejection fraction).

A total of 6,263 patients were randomly allocated to dapagliflozin, 10mg once daily, or placebo. The average age of participants was 72 years and 44% were women. The average left ventricular ejection fraction was 54%, and 18% of patients previously had an ejection fraction of 40% or less.

At randomisation, 77% of patients were taking an ACE inhibitor, angiotensin receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor (ARNI), 83% were taking a beta blocker and 43% were taking a mineralocorticoid receptor antagonist (MRA).

Published simultaneously in the NEJM (link), the results showed that over a median 2.3 years, follow up, the primary outcome occurred in 512 of 3,131 patients (16.4%) in the dapagliflozin group and 610 of 3,132 patients (19.5%) in the placebo group (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.73–0.92; p<0.001).

Among components of the primary endpoint, worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and 455 patients (14.5%) in the placebo group (HR 0.79; 95% CI 0.69–0.91), and cardiovascular death occurred in 231 (7.4%) and 261 (8.3%) patients, respectively (HR 0.88; 95% CI 0.74–1.05).

Secondary outcomes including total heart failure hospitalisations and cardiovascular death and total symptom burden, were also reduced in patients receiving dapagliflozin compared with placebo.

Professor Solomon said it was notable that the benefits were consistent across prespecified subgroups, with similar benefits in patients with ejection fraction at, below, or above 60%, those with heart failure with improved ejection fraction, as well as in patients who were hospitalised recently, and was accompanied by improvement in symptoms.

“Taken together with previous research in heart failure patients with reduced ejection fraction, these data suggest that dapagliflozin is effective regardless of ejection fraction and support the use of SGLT2 inhibitors as foundational therapy in all patients with heart failure,” he said

The study was funded by AstraZeneca.

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