Patients with low plasma renin levels had a more pronounced blood pressure (BP) reduction with spironolactone/dapagliflozin vs. dapagliflozin alone, in addition to seeing a more favorable impact on cardiovascular structure and function, while aldosterone levels exhibited no predictive value in treatment response, according to an analysis from the SOGALDI-PEF trial published in JACC: Heart Failure.

João Pedro Ferreira, MD, PhD, et al., included 106 patients with heart failure with preserved ejection fraction. Plasma renin and aldosterone levels were measured at baseline and throughout the study period with a median baseline renin level of 29.7 mU/L. Patients treated with dapagliflozin alone and spironolactone/dapagliflozin combination for 12 weeks were evaluated in this analysis.

Patients with low renin levels (≤21 mU/L) had higher BP, serum sodium, lateral E/e', pulse wave velocity and peripheral edema vs. patients with higher renin levels. The authors found that renin levels modified the treatment effect on BP. Compared with dapagliflozin alone, spironolactone/dapagliflozin combination reduced systolic BP by 10.9 mm Hg (95% CI, –16.4 to –5.4 mm Hg) in patients with low renin. There was no significant effect at higher renin levels.

Trends were similar when looking at echocardiographic parameters and pulse wave velocity. "Beyond BP, patients with low baseline renin exhibited greater reductions in lateral E/e', [pulse wave velocity], and left atrial diameter with both the dapagliflozin and spironolactone/dapagliflozin combination, supporting additional cardiac and vascular benefits in this subgroup," write the authors.

In contrast, aldosterone levels did not predict treatment response, and there was a poor correlation between plasma renin and aldosterone (rho=0.15; p=0.12).

"[I]n SOGALDI-PEF, renin and aldosterone were not correlated, suggesting the classical renin-aldosterone interdependence was not predominant in this setting," state the authors. "BP, echocardiographic parameters and [pulse wave velocity] did not vary significantly across baseline aldosterone strata, whereas [estimated glomerular filtration rate], serum sodium, and spot urinary sodium excretion were lower at higher aldosterone levels."

"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," add Clara Saldarriaga, MD, FACC, and Bertram Pitt, MD, PhD, FACC, in an accompanying editorial comment. "This finding aligns with the evolving understanding of the spectrum of primary aldosteronism, in which low-renin hypertension, regardless of circulating aldosterone levels, may reflect autonomous aldosterone production and enhanced mineralocorticoid pathway activation."