{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:13:38Z","timestamp":1770066818368,"version":"3.49.0"},"reference-count":39,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Heart"],"accepted":{"date-parts":[[2003,10,27]]},"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:p>\n                  <jats:bold>Objectives:<\/jats:bold> 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\u2013II congestive heart failure (CHF) taking optimal treatment (including \u03b2 blockers).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> Double blind, crossover study comparing 12.5\u201350 mg\/24 hours spironolactone (three months) with placebo in 43 patients with class I\u2013II CHF taking ACE inhibitors and \u03b2 blockers.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> Acetylcholine induced vasodilatation improved with spironolactone (p \u200a=\u200a 0.044). Vascular ACE activity fell (p \u200a=\u200a 0.006). QTc and QTd fell (mean (SD) QTc 473 (43.1) ms with placebo, 455 (35.4) ms with spironolactone, p \u200a=\u200a 0.002; QTd 84.5 (41.3) ms with placebo, 72.1 (32.3) ms with spironolactone, p \u200a=\u200a 0.037). \u03b2-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 \u200a=\u200a 0.039; PIIINP 3.767 (1.157) \u03bcg\/ml with placebo, 3.156 (1.123) \u03bcg\/ml with spironolactone, p \u200a=\u200a 0.000).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> 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 \u03b2 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.<\/jats:p>","DOI":"10.1136\/hrt.2003.017368","type":"journal-article","created":{"date-parts":[[2004,6,14]],"date-time":"2004-06-14T16:48:11Z","timestamp":1087231691000},"page":"765-770","source":"Crossref","is-referenced-by-count":114,"title":["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"],"prefix":"10.1136","volume":"90","author":[{"given":"J E","family":"Macdonald","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A D","family":"Struthers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2004,6,14]]},"reference":[{"key":"2025101714005259000_90.7.765.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"2025101714005259000_90.7.765.2","first-page":"1309","volume":"384","year":"2003","journal-title":"N Engl J Med"},{"key":"2025101714005259000_90.7.765.3","unstructured":"Struthers AD. 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