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Spironolactone for Patients with Severe Heart Failure

Patients with heart failure have elevated plasma levels of aldosterone. This hormone's renal effects (i.e., sodium retention and potassium excretion) are well known, but research suggests that aldosterone also may cause myocardial and vascular fibrosis and baroreceptor dysfunction.

In this international industry-sponsored study, researchers randomized 1,663 patients with class III or IV heart failure and an ejection fraction of no more than 35 percent to receive either the aldosterone-receptor blocker spironolactone (25 mg daily) or placebo. Additional therapies included loop diuretics (100 percent of subjects), ACE inhibitors (94 percent), digitalis (73 percent), and beta-blockers (10 percent). Patients with serum creatinine above 2.5 mg/dl or serum potassium above 5.0 mmol/l were excluded.

The study was stopped after an average follow-up of 2 years: At that point, highly significant reductions in overall mortality (35 percent vs. 46 percent), cardiac death (27 percent vs. 37 percent), and hospitalization events for cardiac causes (515 vs. 753) were observed for spironolactone compared with placebo. Serious hyperkalemia was not a problem for either group in this study.

Comment: Spironolactone had an impressive impact on morbidity and mortality in this study, and it was tolerated well. According to the authors, several mechanisms are probably responsible for these benefits. Further research is necessary to determine whether the drug has a role in therapy for less severe heart failure.

— AS Brett

Published in Journal Watch General Medicine September 10, 1999

Citation(s):

Pitt B et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999 Sep 2 341 709-717.

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