DOCTOR'S VIEW ARCHIVE
Heart Failure ... Old Drug, New Therapy
The New England Journal of Medicine removed the embargo on an unpublished article (1999) and accompanying editorial about the clinical implications of an advance in the treatment of heart failure. The advance involves a drug called spironolactone (pronounced spi-ro-no-lac-tone) that has been manufactured by G.D. Searle & Co. for some years under the brand name of Aldactone and is available as a generic drug. The news about spironolactone is twofold:
The research was reported by Bernard Pitt and colleagues in what was called the Randomized Aldactone Evaluation Study (RALES). The RALES study was unusually far-flung. It took place on 5 continents in 15 countries -- Belgium, Brazil, Canada, France, Germany, Japan, Mexico, The Netherlands, New Zealand, South Africa, Spain, Switzerland, the United Kingdom, the U.S. and Venezuela. At 195 medical centers, a grand total of 1663 patients with symptomatic heart failure were studied. All received standard care and, in addition, they were assigned randomly (by chance alone) to receive spironolactone or a placebo, a blank that looked just like spironolactone.
Results of the research
The RALES study demonstrated that patients who received spironolactone had a sizable reduction in the chance of being hospitalized for heart problems and they had significant improvement in functional status. These healthy responses were evident within several months after enrollment in the RALES study and persisted throughout the two-year duration of the study.
Congestive heart failure and aldosterone
Congestive heart failure is a syndrome that arises from under- oxygenated tissues and congested tissues. By retaining salt, the kidneys work counter to the heart, lungs, and liver in heart failure. There is a "dysfunctional relationship" between the kidney and these other organs that normally cooperate to preserve circulatory balance. This dysfunctional relationship involves a substance called aldosterone.
Spironolactone blocks the action of aldosterone, a hormone that is released by the adrenal glands into the blood stream. Aldosterone acts upon the kidneys to encourage the retention of sodium in the blood and promote the loss of magnesium and potassium into the urine. Since the blockade of aldosterone receptors by spironolactone substantially reduces the risk of both morbidity and death among patients with severe heart failure, it is becoming abundantly clear that aldosterone plays an important role in the events leading up to and surrounding heart failure.
Implications for care
If kidney function is all right, the use of a combination of a diuretic (water pill) and spironolactone allows the dose of the diuretic and the amount of supplemental potassium to be reduced. Dr. Weber adds that: "When properly monitored, this therapeutic approach should reduce the risk of death among patients with this common and serious disorder."
Just as old dogs occasionally do learn new tricks, old drugs like spironolactone sometimes show new therapeutic potential.
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, , for the Randomized Aldactone Evaluation Study Investigators: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. New Engl J Med, in press, 1999. (Original report)
Weber KT: Aldosterone and Spironolactone in Heart Failure. New Engl J Med, in press, 1999. (Editorial)
Last Editorial Review: 2/1/2005
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