Use of the aldosterone antagonist spironolactone may yield clinically important reductions in blood pressure (BP) in older patients at risk of heart failure (HF), results of a study in the European Heart Journal – Cardiovascular Pharmacotherapy suggest.

The findings are from the prospective, multicenter, open-label, randomized HOMAGE (Heart Omics in Aging) trial, which included 527 patients (median age, 73 years; 26% female) considered at risk for HF. Patients were randomly assigned to either spironolactone at a dose of 25- to 50-mg/day (n = 265) or usual care alone (n = 262) for up to 9 months. The investigators assessed sitting BP at baseline, at 1 month, and at 9 months. Median patient follow-up time was 8.9 months.

In addition to evaluating the effect of spironolactone on risk for HF, the investigators assessed whether its BP-lowering effect might be more pronounced among patients with lower levels of renin, noting that renin “can be a good surrogate for sodium retention.”


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A history of hypertension was reported in more than 75% of patients. The mean baseline BP was 142/78 mmHg. Patients who had higher BP levels were older, more likely to have diabetes, less likely to have coronary artery disease, and presented with greater left ventricular mass and left atrial volume.

Treatment with spironolactone changed systolic BP by −10.3 (95% CI, −13.0 to −7.5) mmHg and diastolic BP by −3.2 (−4.8 to −1.7) mmHg by last visit compared with usual care (P <.001 for both). A significantly greater proportion of patients treated with spironolactone had controlled BP <130/80 mmHg by the last visit (36 vs 26%; P =.014). Lower renin levels at baseline were predictive of a greater response to spironolactone (P =.041), a result that the authors noted was also reported in the PATHWAY-2 trial.

A limitation of this study was the inclusion of only BP values obtained in the clinic vs those recorded at home or in ambulatory settings. However, the authors noted that their findings may nevertheless “be regarded as robust,” given the consistency of the clinical effects seen in the study subgroups and the similar results reported in other settings and populations.

The investigators concluded that spironolactone “had a clinically important BP-lowering effect and should be considered for lowering blood pressure in patients who are at risk of developing HF.”

In discussing their findings regarding renin and BP, they wrote that in HOMAGE, “patients with lower baseline renin had higher systolic and diastolic BP, similar to the findings of other cohorts. Therefore, spironolactone targeting the low renin physiology, can improve BP control.”

Reference

Ferreira JP, Collier T, Clark AL, et al. Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial. Published online April 2, 2021. Eur Heart J Cardiovasc Pharmacother. doi:10.1093/ehjcvp/pvab031