In HFpEF patients with low renin levels (≤21 mU/L), the spironolactone and dapagliflozin combination reduced systolic blood pressure by 10.9 mm Hg compared with dapagliflozin alone.
RCT (n=106)
crossover
Does the combination of spironolactone and dapagliflozin reduce blood pressure more than dapagliflozin alone in patients with HFpEF, and is this effect modified by baseline renin levels?
Low plasma renin levels (≤21 mU/L) predict a more pronounced blood pressure reduction and favorable cardiovascular structural changes with the combination of spironolactone and dapagliflozin compared to dapagliflozin alone in patients with HFpEF.
Mean Difference: -10.9 (95% CI -16.4–-5.4)
p-value: p=0.007
BACKGROUND: Hypertension and heart failure with preserved ejection fraction (HFpEF) often coexist, and sodium retention is a common feature of both conditions. Renin levels are suppressed in the setting of sodium overload and may modulate the blood pressure (BP) response to mineralocorticoid receptor antagonists (MRAs). The role of renin and aldosterone, and their influence on the response to dapagliflozin, spironolactone, and their combination, has not been tested in HFpEF. OBJECTIVES: The aim of this study was to assess the role of renin and aldosterone in patients with HFpEF enrolled in the SOGALDI-PEF (Dapagliflozin With or Without Spironolactone for HFpEF) trial. METHODS: Plasma renin and aldosterone levels were measured at baseline and at each study visit within a crossover design. Two main sequences were evaluated: dapagliflozin alone and spironolactone/dapagliflozin combination, each administered for 12 weeks. RESULTS: A total of 106 patients were included. The median (percentile 25-75) renin level at baseline was 29.7 mU/L (17.6-61.6 mU/L); tertile 1 comprised patients with renin levels ≤21 mU/L. Compared with patients with higher renin (tertile 2/tertile 3), those with lower levels had higher BP (systolic blood pressure/diastolic blood pressure), serum sodium, lateral E/e', pulse wave velocity, and peripheral edema. Renin levels, but not aldosterone levels, modified the effect on BP: compared with dapagliflozin alone, the spironolactone/dapagliflozin combination reduced systolic blood pressure by -10.9 mm Hg (95% CI: -16.4 to -5.4 mm Hg) among patients with low renin (tertile 1) but had no significant effect at higher renin levels: tertile 2, -5.6 mm Hg (95% CI: -11.3 to 0.02 mm Hg); and tertile 3, 1.5 mm Hg (95% CI: -4.1 to 7.0 mm Hg) (interaction P trend = 0.007). Echocardiographic parameters and pulse wave velocity followed a similar pattern. The correlation between plasma renin and aldosterone was poor (rho = 0.15; P = 0.12). CONCLUSIONS: Low plasma renin levels (≤21 mU/L) identify a high BP, sodium overload state and predict a more pronounced BP reduction with the spironolactone/dapagliflozin combination compared with dapagliflozin alone. Additional findings support a favorable impact of spironolactone/dapagliflozin in cardiovascular structure and function in patients with low renin levels. Aldosterone levels did not predict treatment response. (Dapagliflozin With or Without Spironolactone for HFpEF SOGALDI-PEF; NCT05676684).
“The observation that low renin levels – independent of aldosterone concentration – identify a subset of patients deriving greater benefit from combination therapy is both clinically relevant and biologically plausible. This finding aligns with the evolving understanding of the spectrum of primary...”
Published in JACC: Heart Failure, this analysis of the SOGALDI-PEF trial suggests that baseline renin levels, but not aldosterone, predict the blood pressure response to spironolactone in patients with HFpEF. This finding is generating discussion about using renin levels to personalize antihypertensive therapy in this complex patient population.
Ferreira et al. (2026) conducted an RCT in Hypertension and heart failure with preserved ejection fraction (HFpEF) (n=106). Spironolactone and dapagliflozin combination vs. Dapagliflozin alone was evaluated on Systolic blood pressure reduction in patients with low renin (tertile 1) (MD -10.9 mm Hg, 95% CI -16.4 to -5.4, p=0.007). In HFpEF patients with low renin levels (≤21 mU/L), the spironolactone and dapagliflozin combination reduced systolic blood pressure by 10.9 mm Hg compared with dapagliflozin alone.