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Randomized Controlled Trial
. 2025 Aug 5;86(5):320-333.
doi: 10.1016/j.jacc.2025.05.033.

Sodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction: The SOGALDI-PEF Trial

João Pedro Ferreira  1 , Francisco Vasques-Nóvoa  2 , Francisca Saraiva  3 , Ana C Oliveira  3 , Jorge Almeida  4 , Ana Beatriz Batista  3 , Arsénio Barbosa  4 , Ana Filipa Ferreira  3 , Cátia Costa  5 , Silvia O Diaz  3 , Diogo Santos-Ferreira  6 , Fernando Friões  4 , Cândida Goncalves  3 , João Tiago Guimarães  7 , Marta Leite  5 , Pedro Marques  2 , Joana Mascarenhas  8 , Maria Inês Matos  4 , Catarina Pereira  8 , Pedro Rodrigues  4 , Abhinav Sharma  9 , Gualter Silva  5 , Inês Pereira-Sousa  10 , Carla Sousa  11 , Faiez Zannad  12 , Joana Pimenta  13 , Ricardo Fontes-Carvalho  6 , Adelino Leite-Moreira  14
Affiliations
Randomized Controlled Trial

Sodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction: The SOGALDI-PEF Trial

João Pedro Ferreira et al. J Am Coll Cardiol. .

Abstract

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists improved heart failure outcomes in heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction; however, their combination was not tested in a randomized manner. Whether the SGLT2i/mineralocorticoid receptor antagonist combination offers benefits compared to SGLT2i alone requires dedicated trials.

Objectives: This study aims to compare the efficacy and safety of dapagliflozin/spironolactone combination vs dapagliflozin alone in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction.

Methods: This was a prospective randomized open, blinded endpoint crossover trial. A sample size of 108 patients was powered to detect 0.15 Log N-terminal pro-B-type natriuretic peptide (NT-proBNP) difference between the dapagliflozin/spironolactone combination and dapagliflozin alone sequences study primary outcome. Each treatment sequence was given for 12 weeks.

Results: One hundred eight patients were randomized. The median age was 76 years (Q1-Q3: 71-81 years), 57% were women, estimated glomerular filtration rate (eGFR) 72 mL/min/1.73 m2 (Q1-Q3: 49-89 mL/min/1.73 m2), potassium 4.3 mmol/L (Q1-Q3: 4.0-4.6 mmol/L), and 45% had diabetes. The median NT-proBNP was 746 pg/mL (Q1-Q3: 401-1,493 pg/mL) and median LogNT-proBNP 6.6 Log-units (Q1-Q3: 6.0-7.3 Log-units). Compared to dapagliflozin, dapagliflozin/spironolactone combination reduced LogNT-proBNP levels: -0.11 (95% CI: -0.22 to -0.01) Log-units (P = 0.035) corresponding to an 11% relative reduction and increased the odds of reaching ≥20% NT-proBNP reduction (OR: 2.27; 95% CI: 1.16-4.44; P = 0.016). Compared to dapagliflozin, dapagliflozin/spironolactone combination reduced systolic blood pressure (-5.2 mm Hg; 95% CI: -8.4 to -2.0 mm Hg), reduced Logurinary-albumin-to-creatinine ratio (-0.32 Log; 95% CI: -0.54 to -0.11 Log) decreased eGFR (-6.4 mL/min/1.73 m2; 95% CI: -8.3 to -4.4 mL/min/1.73 m2), and increased serum potassium (+0.32 mmol/L; 95% CI: 0.23-0.41 mmol/L) and the frequency of serum potassium (>5.5 mmol/L: 5 [4.8%] vs 1 [0.9%]).

Conclusions: Dapagliflozin/spironolactone combination reduced NT-proBNP more than dapagliflozin. A greater eGFR decline and potassium increase was observed with dapagliflozin/spironolactone combination (SOGALDI-PEF [Dapagliflozin With or Without Spironolactone for HFpEF]; NCT05676684).

Keywords: dapagliflozin; heart failure with preserved ejection fraction; spironolactone.

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Conflict of interest statement

Funding Support and Author Disclosures This research was conducted with support from AstraZeneca–Produtos Farmacêuticos, Lda. (Grant number ESR-20-20771) and national funds through FCT-Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center UnIC (UIDB/00051/2020 and UIDP/00051/2020). FCT PhD grants support ABB (UI/BD/154952/2023), ACO (UI/BD/150647/2020) and IPS (UI/BD/154953/2023). Dr J.P. Ferreira has received research support from AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Amgen, Bial, and Salamandra. Dr Vasques-Nóvoa has received consulting or speaker fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Ultragenyx. Dr Inês Matos has received speaker fees from Novartis. Dr Sharma has received consulting fees/research support from Janssen, Roche Diagnostics, AstraZeneca, Bayer Inc, Boehringer Ingelheim, Novartis, Servier, and Novo Nordisk. Dr Pimenta has received consulting/speaker fees from AstraZeneca, Bayer, Bial, Boehringer Ingelheim, GSK, Lilly, Merck, Novartis, Pfizer, Roche diagnostics, Servier, and CSL Vifor. Dr Fontes-Carvalho has received consulting/speaker fees from Amgen, Amarin, AstraZeneca, Bayer, Bial, Boehringer-Ingelheim, BMS, Servier, Lilly, MSD, Medinfar, Menarini, Mylan, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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