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

Abstract

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 b 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.

Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Effect of Aldosterone Antagonism With Eplerenone on Ventricular Remodeling in Patients With Mild-to-Moderate Heart Failure and Left Ventricular Systolic Dysfunction

“…In a 40-patient randomized trial of 3 months duration, Berry et al 17 found that spironolactone improved BNP and PIIINP levels compared with placebo but had unfavorable effects on a quality-of-life measure and on serum creatinine. Chan et al 18 reported on 51 patients with mild-to-moderate HF, 70% of whom were on BBs.…”

Effects of ivabradine therapy on heart failure biomarkers

“…It is the inactive split product of the BNP [22]. NT-proBNP levels often decline after initiation and up-titration of HF therapy such as vasodilators and aldosterone blockers [23][24][25]. Persistently elevated (or rising) levels of NT-proBNP are predictive of poor outcome [26].…”

Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases

“…De ce fait, en dépit des nombreuses publications faisant état d'altérations de ces marqueurs dans les maladies cardiaques responsables de la survenue d'une fibrose ou de la destruction du réseau de collagène au niveau du myocarde, seuls quelques uns d'entre eux satisfont à cette exigence et apportent donc des informations quant à leur utilité clinique potentielle (Tableau 4 [20][21][22][23][24][25][28][29][30][31]40,[61][62][63][64][65][66][67][68] ). Il est à noter que certaines de ces études font état d'altérations intéressant plus d'un biomarqueur, ce qui permet d'envisager l'emploi combiné de plusieurs marqueurs afin de recueillir davantage de renseignements sur les perturbations du métabolisme du collagène dont il est ici question.…”

“…For instance, it has been reported that serum PICP decreases in hypertensive patients being treated with angiotensin type 1 receptor antagonists 28,[61][62][63][64] or HF patients treated with the loop diuretic torasemide, 27,29 PIIINP decreases in HF patients treated with aldosterone antagonists, [65][66][67][68] CITP and MMP-1 increase in hypertensive patients treated with angiotensin-converting enzyme inhibitors, 69,70 and CITP decreases in hypercholesterolemic patients treated with statins. 71 Thus, the potential influence of previous pharmacological treatment must be carefully considered in studies assessing serum biomarkers of collagen metabolism in cardiac patients.…”