Vnitr Lek 2002, 48(8):767-772
[The significance of aldosterone in chronic heart failure: the RALES study].
- Ustav patologickej fyziológie Lekárskej fakulty UK, Bratislava, Slovenská republika.
Reduction of excessive neurohumoral activation in chronic heart failure (CHF) improves the prognoses. In addition to reduction of angiotensin production or angiotensin II action and the influence of the sympathoadrenal system also blocking of aldosterone effects becomes part of the therapeutic procedure in patients with CHF. Excessive systemic and probably also local aldosterone production promotes undesirable fluid retention, hypokalaemia and hypomagnesaemia, induction of hypertrophy and fibrosis of the heart muscle and blood vessels and the development of endothelial dysfunction, peripheral vasoconstriction and depression of the baroreflex. In addition to classical effects also the existence of a rapid, so-called non-genomic effect of aldosterone is assumed. Adding a blocker of aldosterone receptors to ACE inhibition was not recommended due to possibility development of hyperkalaemia. Later it was revealed that ACE inhibitors are unable to block sufficiently the action of aldosterone and that addition of spironolactone in small amounts to ACE inhibition and diuretics does not cause in patients with CHF a major increase of the potassium level. In the RALES study (Randomized Aldacton Evaluation Study) comprising 1663 patients with serious heart failure (NYHA III, IV) addition of 25 mg spironolactone to standard treatment with ACE inhibitor, diuretic and as rule also digoxin reduced the mortality by another 30% as compared with the addition of placebo. Undesirable effects were minimal. As to potential protective mechanisms of spironolactone the greatest importance is ascribed to the reduction of excessive fibrosis of the heart muscle. Spironolactone reduces the level of the circulating N-terminal aminopeptide procollagen type III the high level of which is associated with deterioration of the prognosis.
Keywords: Aldosterone, physiology, ; Heart Failure, drug therapy, ; Humans; Mineralocorticoid Receptor Antagonists, therapeutic use, ; Spironolactone, therapeutic use,
Published: August 1, 2002 Show citation