Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists have individually improved outcomes in heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF). However, the efficacy and safety of combining these agents remain untested in randomized trials, necessitating dedicated studies to evaluate potential synergistic benefits.
This study aimed to compare the efficacy and safety of dapagliflozin combined with spironolactone versus dapagliflozin alone in patients with HFpEF or HFmrEF, focusing on changes in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and other cardiovascular and renal outcomes.
The SOGALDI-PEF trial was a prospective, randomized, open-label, blinded-endpoint crossover study involving 108 patients with HFpEF or HFmrEF. Patients were assigned to receive either dapagliflozin alone or dapagliflozin with spironolactone for 12 weeks per treatment sequence. The primary outcome was the difference in Log NT-proBNP levels, with a sample size powered to detect a 0.15 Log-unit difference. Secondary outcomes included changes in systolic blood pressure, urinary albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), and serum potassium levels.
The cohort had a median age of 76 years (Q1-Q3: 71–81), with 57% women, 45% with diabetes, and a median NT-proBNP of 746 pg/mL (Q1-Q3: 401–1,493 pg/mL). The dapagliflozin/spironolactone combination reduced Log NT-proBNP by 0.11 Log-units (95% CI: −0.22 to −0.01; P = 0.035), equating to an 11% relative reduction, and increased the odds of achieving a ≥20% NT-proBNP reduction (OR: 2.27; 95% CI: 1.16–4.44; P = 0.016). Compared to dapagliflozin alone, the combination lowered systolic blood pressure by 5.2 mm Hg (95% CI: −8.4 to −2.0), reduced Log urinary albumin-to-creatinine ratio by 0.32 Log-units (95% CI: −0.54 to −0.11), decreased eGFR by 6.4 mL/min/1.73 m² (95% CI: −8.3 to −4.4), and increased serum potassium by 0.32 mmol/L (95% CI: 0.23–0.41), with hyperkalemia (>5.5 mmol/L) in 4.8% versus 0.9% of patients.
The dapagliflozin/spironolactone combination significantly reduced NT-proBNP levels and improved secondary cardiovascular outcomes compared to dapagliflozin alone in HFpEF and HFmrEF patients. However, it was associated with a greater eGFR decline and increased serum potassium, indicating a need for careful monitoring in clinical practice (SOGALDI-PEF; NCT05676684).
