JACC. Heart failure
May 26, 2026 · via Europe PMC
Renin, Aldosterone, and Treatment Response to Dapagliflozin, Spironolactone, and Their Combination: An Analysis From SOGALDI-PEF.
Ferreira JP, Marques P, Neves JS, +9 more, SOGALDI-PEF Investigators.
AI summary — for doctors, generated from the abstract only
In a trial of heart failure patients with preserved ejection fraction, those with low baseline renin levels (indicating sodium overload) showed a much larger blood pressure reduction when spironolactone was added to dapagliflozin, while those with higher renin levels saw little added benefit, suggesting renin testing could help identify who benefits most from this drug combination.
What was studied
An analysis from the SOGALDI-PEF crossover trial of 106 patients with heart failure with preserved ejection fraction, measuring plasma renin and aldosterone levels at baseline and throughout a crossover comparing dapagliflozin alone versus spironolactone plus dapagliflozin (each for 12 weeks), examining whether renin or aldosterone levels predicted blood pressure and cardiac structural/functional responses to treatment.
Key findings
- Patients with lower baseline renin (≤21 mU/L, the lowest tertile) had higher blood pressure, higher serum sodium, and more signs of fluid overload compared to those with higher renin levels.
- Renin level, but not aldosterone level, significantly modified the blood pressure response: adding spironolactone to dapagliflozin reduced systolic blood pressure by 10.9 mmHg in the lowest renin tertile, with no significant effect in higher renin tertiles (interaction p-trend = 0.007).
- Echocardiographic measures and arterial stiffness followed a similar pattern favoring the combination specifically in low-renin patients, while plasma renin and aldosterone levels correlated poorly with each other (rho=0.15, not statistically significant).
Clinical relevance
These findings suggest that measuring plasma renin could help identify a specific subgroup of heart failure with preserved ejection fraction patients, those with low renin and sodium overload, who are most likely to benefit from adding spironolactone to dapagliflozin for blood pressure and cardiac structural improvement, which could support a more personalized approach to combination therapy in this condition.
Who should care
Limitations
This is a relatively small crossover trial (106 patients) examining a biomarker-based subgroup analysis rather than a trial specifically designed and powered around renin-stratified treatment allocation; findings on cardiac structural improvement would benefit from confirmation with harder clinical outcomes in a larger trial.
A simple blood test for a hormone called renin could help identify which heart failure patients with preserved pumping function get the biggest blood pressure benefit from adding a potassium-sparing diuretic to their standard treatment.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
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).
DOI
10.1016/j.jchf.2026.103111
PMID
42201301
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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