From science to bedside: clinical rationale for the RALES study

A large body of evidence indicates that secondary aldosteronism in heart fa ilure (HF) has deleterious effects. Hypokalaemia and magnesium depletion pr omotes cardiac arrhythmias, which are common in CHF and may lead to sudden cardiac death. Aldosterone can blunt the baroreflex and inhibit the extramu ral 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 al dosterone levels have been shown to stimulate collagen synthesis by myocard ial fibroblasts leading to collagen accumulation and myocardial fibrosis, w hich reduce diastolic ventricular compliance. The suppressive effect of angiotensin-converting enzyme (ACE) inhibitors on aldosterone production may be inadequate since continuous ACE inhibitor th erapy 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 venou s capacitance, which may increase preload and afterload despite full ACE in hibition. Spironolactone prevents potassium and magnesium loss, and animal experiments have proven its antifibrotic effect. Both characteristics may r educe the risk for ventricular arrhythmias and mortality. Spironolactone ha s a vasodilatory action not only through aldosterone antagonism but also th rough other mechanisms unrelated to aldosterone-specific antagonism. Furthe rmore, spironolactone causes sodium and water loss. Both effects will reduc e preload and may decrease the worsening of the heart failure process and t he need for hospital admission. Basic scientific data and clinical use of spironolactone show that aldoster one antagonists are a powerful therapeutic tool in the treatment of HF. (C) The European Society of Cardiology.