Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker

Aims: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild–moderate HF treated with an ACE inhibitor and beta‐blocker. Methods and results: Randomised, double‐blind, parallel‐group, 3‐month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%. The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B‐type natriuretic peptide (BNP) −53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P =0.04, ii) pro‐collagen type III N‐terminal amino peptide (PIIINP) −0.6(0.2) μmol/L and +0.02(0.2) μmol/L, P =0.02 and iii) creatinine +10.7(3.2) μmol/L and −0.3(2.6) μmol/L, P =0.01. Compared with placebo, spironolactone therapy was associated with a reduction in self‐reported health‐related quality of life: change in visual analog score: −6 (3) vs. +6 (4); P =0.01. No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. Conclusion: In patients with mild–moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit–risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.