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

Sattar, N. et al. (2024) Body mass index and cardiorenal outcomes in the EMPEROR-Preserved trial: principal findings and meta-analysis with the DELIVER trial. European Journal of Heart Failure, (doi: 10.1002/ejhf.3221) (PMID:38558521) (Early Online Publication)

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/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2 and ≥40 kg/m2) were examined, and a meta-analysis conducted with DELIVER. Forty-five percent had a BMI of ≥30 kg/m2. 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 m2 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.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lee, Matthew and Ferreira, Mr Joao Pedro and Sattar, Professor Naveed
• Authors: Sattar, N., Butler, J., Lee, M. M.Y., Harrington, J., Sharma, A., Zannad, F., Filippatos, G., Verma, S., Januzzi, J. L., Ferreira, J. P., Pocock, S. J., Pfarr, E., Ofstad, A. P., Brueckmann, M., Packer, M., and Anker, S. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 01 April 2024
• Copyright Holders: Copyright © 2024 The Authors
• First Published: First published in European Journal of Heart Failure 2024
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	SCMH - Cardiovascular & Metabolic Health