Hope for Unhealthy Hearts

By J. MADELEINE NASH/DALLAS

Doctors have long known about the link between heart disease, America's No. 1 killer, and high levels of cholesterol in the blood. Yet physicians have been reluctant to treat patients with drugs that lower cholesterol. Not only are the medications expensive (as much as $1,000 a year), but they also have been dogged by an inexplicable anomaly: in studies of patients who take them, declines in fatal heart attacks have been offset by a mysterious rise in deaths from other causes. As attractive as the cholesterol-reducing pills might seem, nobody had yet proved that they actually save lives.

Until now. Last week at the American Heart Association meeting in Dallas, a team of Scandinavian scientists presented results of such stunning clarity that doubts about cholesterol drugs may finally be put to rest. In a trial involving nearly 4,500 patients, a drug called simvastatin not only cut harmful cholesterol 35% but also reduced the death rate (compared with a control group) 30%. "This is a seminal study," says Dr. Suzanne Oparil, president of the American Heart Association. "It has profound implications for the practice of medicine."

Today most heart disease is treated as though it were primarily a mechanical malfunction. Clogged arteries are either reopened with the equivalent of a plumber's snake or bypassed by vessels borrowed from other parts of the body. But while such heroic measures can relieve pain and reduce debilitating fatigue, they generally forestall death for only a few years.

The more promising approach is to attack the root cause of heart disease: the family of lipoproteins that carry cholesterol through the bloodstream. There are two main kinds of lipoproteins: high density ("good") and low density ("bad.") As the bad lipoproteins travel through the body, they tear at arterial walls, forming a fat-filled scar tissue called plaque. Remove the irritants, and the arteries begin to heal.

Unfortunately, standard low-fat diets have only a modest effect on most people's blood-cholesterol levels, and, until recently, drugs were not much better. That changed in 1987, when the first of a new class of compounds -- called statins -- was approved for use in the U.S. Statins reduce cholesterol by blocking production of a key enzyme needed to manufacture lipoproteins. Scientists predicted that if a drug like simvastatin were put to a long-term test, it would reduce death rates by one-third.

Which is precisely what happened. The subjects of the Scandinavian study -- all of them heart-disease patients -- were advised to stop smoking and follow sensible diets. In addition, half received daily doses of simvastatin, while the rest took a placebo. The effects were striking. Patients who took the drug registered a 35% drop in levels of bad cholesterol and an 8% rise in good.They also required fewer hospitalizations and surgical procedures. Best of all, they experienced 42% fewer deaths from heart disease and no increase | in deaths from other causes.

Merck & Co., which markets simvastatin under the brand name Zocor (and which funded the study), is expected to enjoy a boost in sales, as will other drug companies that offer competing products. "Anything that lowers cholesterol will produce the same effect," says Dr. Lance Gould of the University of Texas medical school in Houston. As if to underscore that point, a separate study released last week showed that a combination of estrogen and a new form of progesterone can cut cholesterol levels and reduce the risk of heart disease among postmenopausal women as much as 25% -- without serious side effects.

Not everyone with high cholesterol is a good candidate for drug therapy. Otherwise healthy people over the age of 70, a group of experts recently concluded, are not likely to benefit from a rigorous cholesterol-lowering regimen. But for people at high risk of dying from heart disease -- especially the 1.5 million Americans who will suffer heart attacks this year -- the new cholesterol-loweri ng drugs may mean the difference between life and death.