SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper

Abstract Background Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA) reduce heart failure (HF) events in patients with heart failure and mildly reduced or preserved ejection fraction (HFmr/pEF). The randomized comparison of SGLT2i/MRA combination v...

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Main Authors: João Pedro Ferreira, Francisco Vasques‐Nóvoa, Francisca Saraiva, Ana C. Oliveira, Jorge Almeida, Ana Beatriz Batista, Arsénio Barbosa, Ana Filipa Ferreira, Cátia Costa, Diogo Santos‐Ferreira, Fernando Friões, Cândida Goncalves, João Tiago Guimarães, Marta Leite, Pedro Marques, Joana Mascarenhas, Maria Inês Matos, Catarina Pereira, Pedro Rodrigues, Abhinav Sharma, Gualter Silva, Inês Pereira‐Sousa, Carla Sousa, Faiez Zannad, Joana Pimenta, Ricardo Fontes‐Carvalho, Adelino Leite‐Moreira
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.15294
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Summary:Abstract Background Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA) reduce heart failure (HF) events in patients with heart failure and mildly reduced or preserved ejection fraction (HFmr/pEF). The randomized comparison of SGLT2i/MRA combination versus SGLT2i or MRA alone requires further testing in HFmr/pEF. Aims To compare the efficacy (NT‐proBNP change as primary outcome) and safety (potassium, creatinine, and blood pressure changes) of dapagliflozin/spironolactone combination versus dapagliflozin alone (primary comparison) and spironolactone alone (exploratory comparison). Methods SOGALDI‐PEF (SOdium‐Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with preserved ejection fraction; NCT05676684), a proof‐of‐concept investigator‐initiated two‐centre randomized cross‐over trial comparing three arms (dapagliflozin, spironolactone, or both) for three periods of 12 weeks each intercalated by a wash‐out period of 4 weeks. After two independent trials demonstrating efficacy of SGLT2i in HFmr/pEF, a mid‐trial protocol amendment dropped the spironolactone alone sequence and reduced the wash‐out period to 1 week. A sample size of 108 patients was estimated to provide 80% power, at a 0.05 alfa level, to detect a 0.15 LogNT‐proBNP difference between the spironolactone/dapagliflozin combination and dapagliflozin alone sequence. Results SOGALDI‐PEF included 108 patients with a median age of 76 years, 57% women, 42% with atrial fibrillation, 46% with type 2 diabetes, 33% having an eGFR below 60 mL/min/1.73m2, and 93% having an ejection fraction ≥ 50%. The median serum potassium was 4.3 mmol/L, and the median NT‐proBNP was 764 pg/mL. Most patients were treated with renin–angiotensin blockers (68%), beta‐blockers (70%) and loop diuretics (69%). Compared to other HFmr/pEF trials, SOGALDI‐PEF patients were older, were more frequently women, had a high prevalence of atrial fibrillation, and had more often a preserved ejection fraction. Conclusions SOGALDI‐PEF will be the first trial in HFmr/pEF to test the combination of dapagliflozin/spironolactone vs dapagliflozin alone in a randomized manner. SOGALDI‐PEF will provide information on the potential efficacy and safety of concomitant administration of spironolactone with dapagliflozin vs dapagliflozin alone in an elderly population with HFmr/pEF.
ISSN:2055-5822