ROANOKE TIMES
Copyright (c) 1996, Roanoke Times
DATE: Tuesday, January 9, 1996 TAG: 9601100096
SECTION: EXTRA PAGE: 3 EDITION: METRO
COLUMN: personal health
SOURCE: JANE BRODY
Two physician-researchers who previously questioned the economic and medical wisdom of universal cholesterol testing and treatment are now questioning the long-term safety of the leading cholesterol-lowering drugs.
In an article in The Journal of the American Medical Association, Drs. Thomas Newman and Stephen Hulley of the University of California at San Francisco maintain that two classes of drugs, the fibrates and the statins, used by tens of millions of Americans, could possibly cause cancer.
But an editorial by two doctors in the journal disputes the thesis.
At issue is whether a seemingly healthy person with an elevated cholesterol level can expect benefits from long-term use of a cholesterol-lowering medication that would justify any risks associated with the treatment.
The researchers maintain that treatment with the two classes of drugs should be reserved for patients already known to have heart disease or those at very high risk of developing it.
``Cholesterol-lowering drugs are not like most drugs, which are given to people who are sick in hopes of making them well,'' Newman said in an interview.
``You can tolerate greater risks in people who are already sick. But cholesterol-lowering drugs are being taken for decades by people who are well, in hopes of keeping them well. For them the projected benefit is smaller and thus the possible risks are more important. Our concern is that the drugs might be associated with an increase in cancer and that this may not be noticed for 20 or more years.''
Hulley said: ``We don't want people who should be on cholesterol-lowering drugs to become alarmed by our report. People with a high enough short-term risk of developing coronary disease should not worry about the hypothetical possibility of cancer, which could be decades away.''
The evidence for carcinogenicity that the researchers cite is circumstantial, mainly studies showing an increase in cancer in laboratory rodents treated with doses of the drugs.
While they concede that there has been no definitive evidence of a cancer risk among people taking the drugs, they point out that the most popular drugs - the statins - have not been used long enough to have caused cancer among users.
Studies of the older fibrates are worrisome, the researchers maintain, because they reveal a small but statistically significant increase in deaths from noncardiovascular causes including cancer.
For those who need long-term drug treatment, Hulley said that two other kinds of cholesterol-lowering drugs, the resin cholestyramine and the vitamin niacin, appear less likely to have long-term adverse effects.
In the accompanying editorial in the journal, two doctors from the University of Arizona College of Medicine in Tucson discounted the possibility of a cancer risk associated with the fibrates and statins and challenged the evidence on which the concern was based.
Dr. James Dalen, a cardiovascular epidemiologist, and Dr. William Dalton, an oncologist and cancer researcher, stated that rodents are poor predictors of the ability of a chemical to cause cancer in humans. Although nearly all human carcinogens are also carcinogenic in rodents, the reverse is not true.
Furthermore, they said, the doses of the cholesterol-lowering drugs used in the rodent studies are many times greater than what people take.
Countering the editorial comment, Hulley and Newman said that most other drugs, including 85 percent of the drugs used to lower blood pressure, did not cause cancer in rodents.
They argued that it was inappropriate to discount the significance of cancer tests in rodents. They cited the World Health Organization's statement that when data on humans were lacking, it was ``prudent'' to regard evidence of cancer in experimental animals as indicative of a cancer risk to humans.
Newman and Hulley performed no new tests. Rather, they based their warning on rodent studies that had been submitted to the Food and Drug Administration before the drugs were approved for sale.
The drug agency apparently did not consider the findings cause for keeping the medications off the market.
The main hope from the beginning was that these medications would prevent cardiovascular disease, not just delay the inevitable in patients who already had damaged hearts or clogged coronary arteries, Dalen explained.
Although most studies showed that cholesterol-lowering medications had the greatest benefit for cardiac patients, a study in Scotland published in November showed that the statin drugs could prevent the development of heart disease in healthy middle-aged people with high cholesterol levels.
Still, Newman and Hulley questioned the wisdom of treating elevated cholesterol levels in young men and women. ``In general, these are people who are at very low short-term risk of developing heart disease, and it is not clear that the benefits of treatment are worth the risks,'' Newman said.
``If you wait to lower cholesterol when people reach middle age as in the Scottish study, it will work about as well.''
LENGTH: Medium: 90 linesby CNB