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A Forgotten Drug Brings New Hope to Heart-Failure Patients.

Congestive heart failure (CHF) is a chronic disease affecting an increasing number of heart patients. Thanks to modern medicine's clot-busting drugs, bypass surgery, and other dramatic procedures, increasing numbers of people are surviving heart attacks that previously would have been fatal. However, many of these survivors pay a price, with weakened hearts that become increasingly less able to pump blood efficiently. Fluids build up in the lungs, making breathing more difficult; with shortness of breath, the patient can't walk more than a few steps.

CHF was treated 30 to 40 years ago with a drug called Aldactone, which was also used for the high blood pressure that often led to heart failure. Aldactone, manufactured by Searle, blocked the action of the hormone aldosterone, to which medical science used to give considerable attention. Progress is progress, however, and when a new villain--a protein called angiotensin--was identified in the 1980s as an important factor in heart failure, a new class of drugs called ACE inhibitors was developed. By dilating blood vessels and easing the heart's workload, these drugs (along with diuretics) became the standard treatment for CHF--and Aldactone was relegated to the museum of ancient remedies.

However, an expert in heart-muscle mechanics was not convinced that the primary cause of heart failure was an enlarged, overworked heart. Certainly many patients died when their heart pumps gradually gave out, but about the same number died suddenly. As for athletes with enlarged hearts, their muscle fibers were as sound as those in the rest of the body. Dr. Karl Weber, then of the University of Chicago (now at the University of Tennessee School of Medicine in Memphis), discovered that accumulation of fibrous connective tissue between muscle cells made them stiff and unable to contract effectively. What led to the production of this connective tissue? Aldosterone!

Remembering that Aldactone blocked the action of aldosterone, Weber and his colleagues found they could use it to prevent formation of connective tissue in the hearts of their experimental animals. One man--Dr. Alfonso Perez, senior medical director of Searle Corporation--paid attention to the study and began pushing five years ago for a major clinical trial of Aldactone. Reluctantly, the top management at Searle agreed. The drug proved so successful in saving lives that the clinical trial was halted prematurely. The New England Journal of Medicine released the results of the study last summer several weeks before actually publishing it. Combined with ACE inhibitors and diuretics, Aldactone reduced deaths from all causes of heart failure by 30 percent and shortened hospitalization time. Even in the best of studies, ACE inhibitors and diuretics alone had no more than a 15 to 20 percent result.
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Publication:Medical Update
Article Type:Product/Service Evaluation
Date:Jan 1, 2000
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