American Heart Journal · Mar 7, 2026

Empagliflozin and functional aerobic capacity in individuals with increased risk of heart failure: The Empire Prevent Cardiac trial

By Larsen JH, Andersen CF, Jessen MM et al.

BACKGROUND: Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO₂ max in HF with reduced ejection fraction, but the effect on VO₂ max in individuals at risk of HF remain unknown. OBJECTIVE: This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO₂ max, daily physical activity level, and quality of life (QoL) in individuals with overweight or obesity and risk of HF. METHOD: This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index >28 kg/m² and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or type 2 diabetes mellitus were excluded. The primary endpoint was the mean difference in change of VO₂ max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. RESULTS: Among 191 randomized individuals (94 empagliflozin, 97 placebo), 89% had hypertension and 66% ischemic heart disease. At baseline, 69% were male, median age was 68 years, median body mass index 31.9 kg/m², mean left ventricular ejection fraction 65 ± 9%, and mean VO₂ max 18.1 ± 4.3 mL/min/kg. Empagliflozin did not change VO₂ max with an estimated treatment difference of -0.2 mL/min/kg (97.5% confidence interval -1.2 to 0.8), adjusted P = 1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. CONCLUSIONS: Empagliflozin did not affect VO₂ max, physical activity level, or QoL in elderly individuals with overweight or obesity and risk of HF.

doi.org/10.1016/j.ahj.2026.107398Open accessPubMed 41802526Interventions