[The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design]

Abstract

The RALES study has shown that spironolactone reduces the risk of morbidity and mortality both from progressive heart failure and sudden death in patients with NYHA class III or IV heart failure. This favorable effect was clearly independent of a diuretic effect. EPHESUS extended these results to eplerenone in patients with acute myocardial infarction complicated by left ventricular dysfunction and signs of heart failure. Antialdosterone drugs may be effective because they oppose the effects of aldosterone to sodium retention, loss of magnesium and potassium, sympathetic activation, baroreceptor function and vascular compliance. Antialdosterone treatment may also antagonize the effect of aldosterone in promoting cardiac fibrosis. In a RALES substudy baseline serum PIIINP, a marker of extracellular matrix turnover, showed an independent negative correlation with survival and chronic heart failure hospitalizations in the placebo group. Therefore it seems interesting to evaluate the effect of canrenone, an aldosterone receptor blocker, on the progression of left ventricular dysfunction in patients with mild heart failure assuming standard therapy.