Drug Reduces Heart Failure, Study Finds
Deaths and hospitalizations caused by chronic heart failure can be reduced by nearly one-third by giving patients a 30-year-old diuretic called Aldactone, which was not thought to be useful in treating heart patients, according to a new study released Monday.
Nearly 4.7 million Americans suffer from chronic heart failure, in which the heart has grown too weak to pump effectively, and about 250,000 die from it each year. Powerful new drugs, such as ACE inhibitors, beta-blockers and stronger diuretics, were thought to have made Aldactone superfluous in treating heart disease. But researchers have recently found that it has other actions that complement the effects of these drugs.
Adding Aldactone to existing regimens could save 10 or 11 lives for every 100 people treated, according to Dr. P.K. Shah, head of cardiology at Cedars-Sinai Medical Center in Los Angeles.
The international trial of Aldactone--led by University of Michigan researchers--was halted 18 months early because the results were so dramatic. The report, scheduled to be published in the New England Journal of Medicine in September, was released Monday because of its lifesaving implications.
The results “are extremely important for heart failure patient management,” said Dr. Greg Fonarow of UCLA Medical Center. The report, he added, has immediate clinical applications.
Aldactone, known generically as spironolactone, was developed to block the activity of the hormone aldosterone, which promotes salt retention and thereby contributes to high blood pressure. The drug is now used to treat abnormally high production of aldosterone and certain types of hypertension and edema (water retention) that are resistant to other diuretics.
The so-called ACE (angiotensin converting enzyme) inhibitors, which have come into wide use for treating heart failure over the last 15 years, also block aldosterone production, leading many physicians to conclude that spironolactone was not necessary.
Studies in the last five years or so, however, have shown that ACE inhibitors do not block a number of other adverse effects produced by the hormone. Aldosterone causes stiffness of heart and blood vessel tissues, and stimulates production of hormones, such as norepinephrine, that overstimulate the heart and increase the risk of heart failure. Unlike ACE inhibitors, Aldactone can block these hormone actions.
It was also feared that combined use of the two agents, both of which promote potassium retention, could produce dangerously high levels of potassium that could lead to heart stoppage. But such problems can be avoided with careful monitoring of potassium levels, said Dr. Bertram Pitt of the University of Michigan, who headed the trial.
The new study, conducted in 15 countries, enrolled 1,663 patients with severe, chronic heart failure. Such patients have difficulty breathing when they are resting or when undergoing only very mild physical exertion. About one-quarter to one-third of heart failure patients have such severe symptoms, Pitt said.
Half of the subjects received conventional drug treatment, including ACE inhibitors, diuretics and, when necessary, digitalis to stabilize heartbeat. The rest received the same treatment plus Aldactone.
The results were surprisingly positive. There were 386 deaths among the 841 patients who received conventional treatment, but only 284 deaths among the 822 who received Aldactone--a 30% reduction over a two-year period. A similar reduction was observed in the rate of hospitalizations, and most patients who received the drug reported an improvement in symptoms.
“The net effect is pretty dramatic,” Pitt said. “Heart failure is the most common cause of hospitalization, and this can have a tremendous public health impact here and around the world.”
The primary side effect of the drug was gynecomastia, a painful swelling of the breasts among men, which affected up to 10% of those who received it. “But considering the effects of heart failure, that’s a reasonable price to pay,” Pitt said.
G.D. Searle & Co., which sponsored the study although its patent on the drug has expired, is bringing out a newer version that has the same benefit for the heart but that does not cause breast pain, Pitt said. It should be available in about two years.
Because the patent has expired, at least 15 generic versions of the drug are available at a cost of as little as 6 cents per pill, said Dr. Robert Bourge of the University of Alabama at Birmingham.
“That’s a pretty good bang for the buck,” Shah said.
Bourge, a member of the American Heart Assn.’s Council on Clinical Cardiology, called for intensive efforts to educate physicians about spironolactone and other treatments. Despite the proven value of ACE inhibitors and beta-blockers, for example, recent studies have shown that fewer than half of all eligible heart failure patients receive them.
“These drugs don’t do any good if we don’t use them,” he said.
A preliminary version of the results was presented last November at a meeting of the American Heart Assn., “but the word has not really gotten out to most physicians,” Pitt said.
