Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment

Objectives: To examine whether the favourable effects on endothelial function, vascular angiotensin
converting enzyme (ACE) activity, cardiac remodelling, autonomic function, and QT intervals of
spironolactone in combination with ACE inhibitor also occur in patients with New York Heart Association
class I–II congestive heart failure (CHF) taking optimal treatment (including b blockers).
Methods: Double blind, crossover study comparing 12.5–50 mg/24 hours spironolactone (three months)
with placebo in 43 patients with class I–II CHF taking ACE inhibitors and b blockers.
Results: Acetylcholine induced vasodilatation improved with spironolactone (p = 0.044). Vascular ACE
activity fell (p = 0.006). QTc and QTd fell (mean (SD) QTc 473 (43.1) ms with placebo, 455 (35.4) ms
with spironolactone, p = 0.002; QTd 84.5 (41.3) ms with placebo, 72.1 (32.3) ms with spironolactone,
p = 0.037). b-Type natriuretic peptide (BNP) and procollagen III N-terminal peptide (PIIINP)
concentrations were also reduced by spironolactone (mean (SD) BNP 48.5 (29.6) pg/ml with placebo,
36.8 (28.5) pg/ml with spironolactone, p = 0.039; PIIINP 3.767 (1.157) mg/ml with placebo, 3.156
(1.123) mg/ml with spironolactone, p = 0.000).
Conclusions: Spironolactone improves vascular function (endothelial function, vascular ACE activity) and
other markers of prognosis (BNP, collagen markers, and QT interval length) in asymptomatic or mild CHF
when added to optimal treatment including b blockade. This gives support to the hypothesis that the
prognostic benefit seen in RALES (randomised aldactone evaluation study) and EPHESUS (eplerenone
postacute myocardial infarction heart failure efficacy and survival study) may also occur in patients with
milder CHF already taking standard optimal treatment.