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

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.

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) micromol/L and +0.02(0.2) micromol/L, P=0.02 and iii) creatinine +10.7(3.2) micromol/L and -0.3(2.6) micromol/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.

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.