Patients with heart failure with preserved ejection fraction (HFpEF) frequently present with hypertension and evidence of sodium overload, but biomarkers associated with differential treatment response remain unclear. An analysis from the SOGALDI-PEF trial published in JACC: Heart Failure assessed whether plasma renin and aldosterone levels were associated with blood pressure response to dapagliflozin alone or combined with spironolactone in patients with HFpEF.

The crossover study included 106 patients who received dapagliflozin alone and spironolactone plus dapagliflozin for 12 weeks each. Plasma renin and aldosterone concentrations were measured at baseline and during follow-up visits to evaluate their association with treatment response.

Findings

• Low renin was defined as plasma renin ≤21 mU/L.
• Compared with patients with higher renin levels, those with low renin had higher systolic and diastolic blood pressure, higher serum sodium, greater pulse wave velocity, higher lateral E/e′, and more peripheral edema.
• Among patients with low renin, spironolactone plus dapagliflozin reduced systolic blood pressure by −10.9 mm Hg (95% CI: −16.4 to −5.4 mm Hg) compared with dapagliflozin alone.
• The blood pressure reduction observed with combination therapy was not significant among patients with higher renin levels.
• The interaction between renin level and systolic blood pressure response was significant (P trend = 0.007).
• Echocardiographic parameters and pulse wave velocity demonstrated similar response patterns according to renin status.
• Aldosterone concentrations were not associated with treatment response, and the correlation between renin and aldosterone levels was weak (rho = 0.15; P = 0.12).

The findings suggest that low plasma renin levels may identify patients with HFpEF and features of sodium overload who experience greater blood pressure reduction with combined spironolactone and dapagliflozin therapy. Aldosterone levels did not predict treatment response.