Body mass index and cardiorenal outcomes in the EMPEROR‐Preserved trial: Principal findings and meta‐analysis with the DELIVER trial

Abstract Aims Both low and high body mass index (BMI) are associated with poor heart failure outcomes. Whether BMI modifies benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in heart failure with preserved ejection fraction (HFpEF) requires further investigation. Methods and results Using EMPEROR‐Preserved data, the effects of empagliflozin versus placebo on the risks for the primary outcome (hospitalization for heart failure [HHF] or cardiovascular [CV] death), change in estimated glomerular filtration rate (eGFR) slopes, change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS), and secondary outcomes across baseline BMI categories (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 and ≥40 kg/m 2 ) were examined, and a meta‐analysis conducted with DELIVER. Forty‐five percent had a BMI of ≥30 kg/m 2 . For the primary outcome, there was a consistent treatment effect of empagliflozin versus placebo across the BMI categories with no formal interaction ( p trend = 0.19) by BMI categories. There was also no difference in the effects on secondary outcomes including total HHF ( p trend = 0.19), CV death ( p trend = 0.20), or eGFR slope with slower declines with empagliflozin regardless of BMI (range 1.12–1.71 ml/min/1.73 m 2 relative to placebo, p trend = 0.85 for interaction), though there was no overall impact on the composite renal endpoint. The difference in weight change between empagliflozin and placebo was −0.59, −1.48, −1.54, −0.87, and − 2.67 kg in the lowest to highest BMI categories ( p trend = 0.016 for interaction). A meta‐analysis of data from EMPEROR‐Preserved and DELIVER showed a consistent effect of SGLT2i versus placebo across BMI categories for the outcome of HHF or CV death. There was a trend toward greater absolute KCCQ‐CSS benefit at 32 weeks with empagliflozin at higher BMIs ( p = 0.08). Conclusions Empagliflozin treatment resulted in broadly consistent cardiac effects across the range of BMI in patients with HFpEF. SGLT2i treatment yields benefit in patients with HFpEF regardless of baseline BMI.