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

J E Macdonald, N Kennedy, A D Struthers

    Research output: Contribution to journalArticle

    117 Citations (Scopus)

    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 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.
    Original languageEnglish
    Pages (from-to)765-70
    Number of pages6
    JournalHeart (British Cardiac Society)
    Volume90
    Issue number7
    DOIs
    Publication statusPublished - 2004

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