Effects of empagliflozin in patients at risk of heart failure: the empire prevent metabolic trial

AIMS: Obesity increases the risk of heart failure (HF), partly due to hypervolaemia and excess epicardial adipose tissue (EAT).We aimed to investigate the effect of the sodium glucose co-transporter 2 inhibitor empagliflozin on estimated extracellular volume (eECV) and ventricular EAT mass in non-diabetic patients with overweight or obesity and risk of HF to evaluate the drug's potential for HF prevention. METHODS: In this randomised, double-blind, placebo-controlled trial, we recruited non-diabetic patients with body mass index (BMI) >28kg/m2 and risk of HF. Patients were randomised 1:1 to 180-days empagliflozin 10 mg or placebo. The primary endpoints were the baseline-adjusted mean differences in change of eECV and ventricular EAT mass in the intention-to-treat population with Bonferroni-adjustment for multiplicity. RESULTS: From September 2021 to July 2024, we randomised 191 patients (empagliflozin: 94, placebo: 97) with median age 68 years and median BMI 31·9 kg/m2. Analyses of eECV and EAT included 191 and 165 patients, respectively. Compared to placebo, empagliflozin significantly reduced eECV [empagliflozin, mean change (SD): -0·154 L (0·257); placebo, mean change: -0·029 L (0·261); estimated treatment difference (ETD): -0·123 L, 97.5% CI: -0·211 to -0·035, padj=0·004] but did not affect EAT mass [empagliflozin, mean change: -2·3 g (13·4); placebo, mean change: -3·7 g (15·8); ETD: 1·5 g, 97·5% CI: -3·8 to 6·7, padj=1.00]. CONCLUSION: In high-risk patients with overweight or obesity, treatment with empagliflozin resulted in a potentially favourable reduction in eECV compared to placebo. Meanwhile, the drug did not affect EAT mass.