Understanding of the role, triggers, and impact of the renin-angiotensin-aldosterone system in cardiovascular disease has significantly broadened. In recent years substantial discoveries have been made regarding the pathophysiology of heart failure, particularly in the area of neurohormonal activation. New interest in therapy with aldosterone antagonists was stimulated by results of a 2-year study of 1663 patients with heart failure that showed a 30% relative risk reduction of death among patients given a subhemodynamic dosage of spironolactone, a nonselective aldosterone antagonist, compared with placebo, in addition to standard therapy of diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, and digitalis.