New research shows that a drug being taken by 25,000 people to lower cholesterol causes fatal heart abnormalities in monkeys on a high-cholesterol diet.
Dow Chemical Co., which manufactures the drug -- Lorelco or probucol -- last week sent a letter to 115,000 doctors warning them to check for abnormal heart rhythms in patients taking the drug.
The letter, sent at the request of the Food and Drug Administration, describes a study in which eight monkeys, given three or more times the normal dose of Lorelco while on a high cholesterol diet, developed changes in electrocardiograms and dangerously irregular heartbeats. Four monkeys died.
A company spokesman said the drug had previously been tested in even higher doses on monkeys fed a normal diet, with no ill effects.
There were 12 mysterious deaths in 32 dogs given the drug in another study several years ago, but later research suggested that Lorelco had made the dogs prone to develop irregular heartbeats in response to a second drug, adrenalin, which they also received.
Monkeys and other animals failed to react the same way when given Lorelco and adrenalin, so the company concluded the drug was dangerous only for dogs, the spokesman said.
He said nine years of tests of Lorelco on humans, and three years of use since the drug was marketed by Dow in 1976, "have not revealed any adverse cardiovascular events in man."
Since the recent deaths in monkeys, company researchers have reviewed electrocardiograms of several hundred patients taking Lorelco. They found "a few" abnormal patterns -- similar to those of the surviving monkeys -- but felt they were explained by the patients' other medical problems.
The letter instructs doctors to caution patients taking Lorelco against a high cholesterol or high fat diet. It suggests they stop the drug in patients whose cholesterol has not been lowered by it, and check electrocardiograms of those who remain on it.
Because the drug is designed to treat high cholesterol, one of the risks factors for heart disease, it is most likely to be prescribed to patients who already have heart problems. Such drugs tend to be given patients who have failed to lower cholesterol through changing their diet -- raising the worry that many patients on Lorelco may indeed be eating high cholesterol foods.
The FDA plans to look more closely at the monkey research at a meeting March 11, an agency press officer said. The agency may decide to change the drug's labeling, restrict its use or remove it from the market. FDA officials met with Dow in late January and urged the company to send the warning, he said.
There still is no real proof that lowering cholesterol prevents heart disease, although some research has suggested it may reduce the overall death rate or improve the chances of patients who have had a heart attack, said Dr. William B. Kannel, director of the prestigious Framingham Study, a long-term research project in Framingham, Mass.
He said many cardiologists urge patients to decrease the cholesterol in their diet, and some patients can halve cholesterol levels simply by changing what they eat. The Dow spokesman said Lorelco, on the average, reduces cholesterol levels only 15 percent more than diet alone.
Another cholesterol-lowering drug, Atromid-S, which is chemically unrelated to Lorelco, has been criticized because of research showing it may cause cancer, liver tumors and gall bladder disease.
"The solution is not a pill to counteract everybody's bad habits, but instead to change the way we live," Kannel said.