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

Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO 2 max in HF with reduced ejection fraction (HFrEF), but the effect on VO 2 max in individuals at risk of HF remain unknown. This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO 2 max, daily physical activity level and quality of life (QoL) in individuals with overweight or obesity and risk of HF. This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index (BMI) >28 kg/m 2 and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or T2D were excluded. The primary endpoint was the mean difference in change of VO 2 max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. 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 BMI 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 VO 2 max with an estimated treatment difference of −0.2 ml/min/kg (97.5% CI -1.2 to 0.8), adjusted P=1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. Empagliflozin did not affect VO 2 max, physical activity level or QoL in elderly individuals with overweight or obesity and risk of HF.