EFFECTIVENESS OF SPIRONOLACTONE ADDED TO AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR AND A LOOP DIURETIC FOR SEVERE CHRONIC CONGESTIVE-HEART-FAILURE (THE RANDOMIZED ALDACTONE EVALUATION STUDY [RALES])

The present study enrolled 214 patients, aged 26 to 83 years, with sym ptomatic New York Heart Association class II through IV congestive hea rt failure. Patients were continued on their previous therapeutic regi mens, which included an angiotensin-converting enzyme (ACE) inhibitor and a loop diuretic with or without digitalis. Patients were randomize d to 1 of 5 parallel treatment groups: placebo or spironolactone at a single daily dose of 12.5, 25, 50, or 75 mg for 12 weeks. Serum levels of creatinine, urea nitrogen, potassium, plasma renin activity, and N -terminal proatrial natriuretic factor (pro-ANF), as well as urinary a ldosterone levels, were measured periodically. Measurements at 12 week s versus baseline values indicated significant increases in plasma ren in activity and aldosterone excretion and significant decreases in sys tolic and diastolic blood pressure and pro-ANF. Hypokalemia (serum pot assium <3.4 mmol/L) occurred in 10% of placebo-treated patients and in 0.5% of the spironolactone group. The incidence of hyperkalemia (seru m potassium greater than or equal to 5.5 mmol/L) was 5% for the placeb o group, whereas it was 5%, 13%, 20%, and 24% for the 12.5-, 25-, 50- and 75-mg spironolactone treatment groups, respectively. Predictors of hyperkalemia included the use of ACE inhibitors other than captopril, ACE inhibitor dose, and baseline elevation of serum creatinine or pot assium levels. Thus, daily doses of 12.5 to 25 mg of spironolactone co administered with conventional therapy of ACE inhibitors, loop diureti cs, and digitalis are relatively safe (provided that serum potassium l evels are monitored) and effective in blocking the effects of aldoster one, while reducing the potential for hypokalemia in patients with hea rt failure.