From science to bedside: Clinical rationale for the RALES study

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A large body of evidence indicates that secondary aldosteronism in heart failure (HF) has deleterious effects. Hypokalaemia and magnesium depletion promotes cardiac arrhythmias, which are common in CHF and may lead to sudden cardiac death. Aldosterone can blunt the baroreflex and inhibit the extramural uptake of catecholamines which also triggers electrical instability and arrhythmias as well as cardiac death. Sodium and water retention produced by excess aldosterone production perpetuates congestion. Elevated plasma aldosterone levels have been shown to stimulate collagen synthesis by myocardial fibroblasts leading to collagen accumulation and myocardial fibrosis, which reduce diastolic ventricular compliance. The suppressive effect of angiotensin-converting enzyme (ACE) inhibitors on aldosterone production may be inadequate since continuous ACE inhibitor therapy may not reduce aldosterone plasma levels which may either remain high or increase during long-term treatment. In chronically treated HF patients aldosterone is inversely correlated with large artery compliance and venous capacitance, which may increase preload and afterload despite full ACE inhibition. Spironolactone prevents potassium and magnesium loss, and animal experiments have proven its antifibrotic effect. Both characteristics may reduce the risk for ventricular arrhythmias and mortality. Spironolactone has a vasodilatory action not only through aldosterone antagonism but also through other mechanisms unrelated to aldosterone-specific antagonism. Furthermore, spironolactone causes sodium and water loss. Both effects will reduce preload and may decrease the worsening of the heart failure process and the need for hospital admission. Basic scientific data and clinical use of spironolactone show that aldosterone antagonists are a powerful therapeutic tool in the treatment of HF. (C) The European Society of Cardiology.

Original languageEnglish (US)
Pages (from-to)A21-A24
JournalEuropean Heart Journal, Supplement
Issue numberA
StatePublished - Feb 10 2000


  • Aldosterone
  • Angiotensin-converting enzyme inhibition
  • Heart failure
  • Spironolactone


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