Article Text
Abstract
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 β 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 β 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). β-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) μg/ml with placebo, 3.156 (1.123) μg/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 β 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.
- ACE, angiotensin converting enzyme
- BNP, β-type natriuretic peptide
- EPHESUS, eplerenone postacute myocardial infarction heart failure efficacy and survival study
- FBFR, forearm blood flow ratio
- HAD, hospital anxiety and depression
- L-NMMA, N-monomethyl-l-arginine
- MLWHF, Minnesota living with heart failure
- NYHA, New York Heart Association
- PIIINP, procollagen III N-terminal peptide
- QTc, corrected QT interval
- QTd, QT dispersion
- QTdc, corrected QT dispersion
- RALES, randomised aldactone evaluation study
- SDNN, standard deviation of all NN intervals
- ValHeFt, valsartan heart failure trial
- heart failure
- spironolactone
- endothelial function
- β-type natriuretic peptide
- aldosterone
- angiotensin converting enzyme
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- ACE, angiotensin converting enzyme
- BNP, β-type natriuretic peptide
- EPHESUS, eplerenone postacute myocardial infarction heart failure efficacy and survival study
- FBFR, forearm blood flow ratio
- HAD, hospital anxiety and depression
- L-NMMA, N-monomethyl-l-arginine
- MLWHF, Minnesota living with heart failure
- NYHA, New York Heart Association
- PIIINP, procollagen III N-terminal peptide
- QTc, corrected QT interval
- QTd, QT dispersion
- QTdc, corrected QT dispersion
- RALES, randomised aldactone evaluation study
- SDNN, standard deviation of all NN intervals
- ValHeFt, valsartan heart failure trial