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

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).