August 13, 2026Journal of the American College of Cardiology20 citations
View Full PaperSodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction
Key Result
In 108 patients, dapagliflozin/spironolactone combination reduced NT-proBNP more than dapagliflozin alone, but caused greater eGFR decline and potassium increase.
Key Points
- This study aims to evaluate the efficacy and safety of dapagliflozin combined with spironolactone versus dapagliflozin alone in heart failure with preserved ejection fraction.
- Prospective randomized open, blinded endpoint crossover trial
- 108 patients were randomized, each treatment sequence was administered for 12 weeks
- Primary outcome measured was the 0.15 Log NT-proBNP difference
- Dapagliflozin/spironolactone combination led to a greater reduction in NT-proBNP compared to dapagliflozin alone
- Notable decline in eGFR and increase in potassium levels was observed with the combination therapy
- Median age of patients was 76 years, with 57% being women
Study Design
Type
RCT (n=108)
Blinding
Open-label, blinded endpoint
Randomization
Crossover
Structured PICO
Does a dapagliflozin and spironolactone combination reduce NT-proBNP more than dapagliflozin alone in patients with HFmrEF and HFpEF?
P
Population
108 patients (median age 76, 57% women) with heart failure with mildly reduced or preserved ejection fraction, treated for 12 weeks per sequence.
I
Intervention
Dapagliflozin and spironolactone combination given for 12 weeks (crossover sequence).
C
Comparator
Dapagliflozin alone given for 12 weeks (crossover sequence).
O
Outcome
Difference in Log N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the dapagliflozin/spironolactone combination and dapagliflozin alone sequences.surrogate
The combination of dapagliflozin and spironolactone provides greater NT-proBNP reduction than dapagliflozin alone in HFmrEF and HFpEF, though it is associated with greater eGFR decline and potassium increase.
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 m 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).
Expert Takes4 quotes
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“Aligning treatment to absolute risk, minimizing therapeutic inertia, and addressing polypharmacy through high-value prescribing are now central to clinical care. SOGALDI-PEF contributes an important piece to this implementation puzzle, helping us refine how we deploy combination therapy to optimize outcomes for our patients and for population health alike.”
Muthiah Vaduganathan, Cardiologist, Brigham and Women's HospitalBrigham and Women's Hospitalauto_pipelineView source