A 40-year-old generic drug that costs just pennies per day could save the lives of tens of thousands of heart failure patients annually and reduce hospital expenditures by billions of dollars, according to a new research report rushed into publication yesterday.

The drug, called spironolactone, has been used for decades as a treatment for water retention. But until now it had never been tested for its ability to treat congestive heart failure, a debilitating syndrome in which the heart becomes unable to pump blood effectively.

Doctors said they were startled by the drug's dramatic potency against the intractable killer, which affects as many as 4.7 million Americans and kills 250,000 in this country every year.

Death rates were cut by 30 percent over two years and hospitalizations by 35 percent. As a result, a panel of overseers shut down the clinical trial involving more than 1,600 severely ill patients 18 months early, saying it would be unethical to continue giving half of the subjects dummy pills.

"This is going to have a major health impact around the world," said Bertram Pitt, the University of Michigan heart researcher who led the research. "The drug is already available, it's cheap, it will keep a lot of people alive and it'll make a lot of people feel better."

The findings will appear in the Sept. 2 issue of the New England Journal of Medicine. But the journal's editors released the report yesterday because many patients could benefit from the news immediately. Only a handful of medical discoveries each year are important enough to merit such treatment, said the journal's editor, Jerome Kassirer.

In an editorial accompanying the report, Karl T. Weber, a heart specialist at the University of Missouri Health Sciences Center, urged that spironolactone -- in combination with standard medicines -- now be considered the "standard of care" for patients with severe heart failure.

The deadly syndrome can arise from various causes. Heart muscle damage from a previous heart attack or infection, chronic high blood pressure or leaky heart valves can leave the heart weakened and unable to pump efficiently. Over time, fluid starts to leak out of blood vessels, causing swelling or edema. The patient grows increasingly fatigued and immobile; breathing becomes labored as fluids begin to fill the lungs, causing a slow suffocation.

About 400,000 new cases are diagnosed each year in this country, and approximately 20 million people suffer from the disease worldwide. Even with good care, half of all people diagnosed with the syndrome die within five years.

The primary treatment for heart failure has been angiotensin converting enzyme inhibitors (so-called ACE inhibitors), which help lower body fluid volume and blood pressure by blocking a key hormonal pathway that normally helps the body retain salt and water. But whereas ACE inhibitors reduce the level of certain water-retention hormones, spironolactone works by blocking one of those hormones' effects.

The hormone is aldosterone, which has long been known to influence salt levels in the body. In recent years, however, scientists have learned that aldosterone also acts directly and menacingly on heart muscle and blood vessels, stiffening them and reducing their ability to expand and contract. Spironolactone clings to the molecular receptors on heart and vessel cells that normally respond to aldosterone, blocking the hormone's ill effects.

The new study (available at http://www.nejm.org on the World Wide Web) involved 1,663 men and women in 15 countries, all diagnosed with severe "type III or type IV" heart failure. About half got standard treatment plus 25 milligrams daily of spironolactone -- a dose much lower than that used to treat water retention. The others received standard treatment and daily placebos.

After an average follow-up time of two years, 46 percent of the placebo patients had died and 35 percent of the spironolactone group had died -- a 30 percent reduction in the risk of dying. Similarly, the frequency of hospitalization from worsening heart failure was 35 percent lower in the spironolactone group. Patients who received the drug experienced a significant reduction in symptoms.

"Eighteen billion dollars per year are spent on hospital treatments for heart failure," said Alfonso Perez, senior medical director of G. D. Searle, which provided the drug (brand name Aldactone) and financed the study. "This is a no-brainer. We can save billions by spending pennies."

The only significant side effect was breast enlargement in men, a result of the drug's tendency to block not only aldosterone receptors but also androgen receptors -- the molecular docking sites that allow the body to respond to masculinizing hormones.

Searle is about to begin a large clinical study of a new drug, eplerenone, which appears to block aldosterone without blocking androgens.

Spironolactone also can increase blood potassium to dangerously high levels, a condition that itself can cause fatal heart attacks. Patients taking it should have those levels monitored, and the drug is not recommended for people who have trouble clearing potassium from their systems because of kidney problems, said Robert Bourge, director of cardiovascular diseases at the University of Alabama at Birmingham.

"It's not a panacea and shouldn't be used for every patient," Bourge said. But he also expressed great enthusiasm for the drug, which he has been prescribing for several years, he said, with an 80 to 90 percent success rate. "This is a way to save lives with a drug that costs less than 10 cents a capsule, wholesale," he said.

Heart Failure Facts

Congestive heart failure is a condition in which the heart can't pump enough blood to meet the needs of the body's other organs. This can result from:

Narrowed arteries

Scar tissue from a past heart attack

High blood pressure

Heart valve or heart muscle disease

Defects present at birth

Infection

Deaths from heart failure (1996)

Men 16,695

Women 27,142

Living with heart failure (1996)

Men 2,200,000

Women 2,300,000

SOURCE: American Heart Association