The use of ACE inhibitors may strongly inhibit the RAAS, but their suppressive effect on aldosterone production may not be satisfactory. Indeed, in hypertension as well as in CHF, continuous treatment with ACE inhibitor did not produce a sufficient decrease in plasma aldosterone level, which remained high or increases eventually during long term use. In one study, patients treated with hefty doses of captopril (300 mg/day) had a doubling of the plasma aldosterone level at the end of 12 months of therapy despite marked decrease in ANG II level. The reasons for the unsatisfactory suppressive effect of ACE inhibitors on plasma aldosterone could be partly due to tachyphylaxis and also very likely due to predominance of the non-RAAS component of the control system for aldosterone production. Urinary clearance of aldosterone may also be reduced in CHF and CRF. On the basis of these understandings, spironolactone (25-50 mg a day) was used in a large multi-centered randomized controlled trial for treatment of congestive heart failure who already were receiving standard therapy with Ace inhibitors, diuretics and digoxin. The study was terminated in midway because interim analysis showed 30% reduction in mortality in the spironolactone treated group as opposed to the control. Of note, the incidence of hyperkalemia in the treatment group was only 1.7% as opposed to 1% in the placebo group. The incidence of gynecomastia was also modest (10% Vs 1%) in spite of use of other drugs like digoxin that are known also to cause gynecomastia.