Carcinogenicity of lipid-lowering drugs.
OBJECTIVE
To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs.


METHODS
Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts.


METHODS
We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans.


RESULTS
All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up.


CONCLUSIONS
Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.
Department of Laboratory Medicine, School of Medicine, University of California, San Francisco, USA.
T B
TB
Newman
S B
SB
Hulley
D000818:Animals; D015197:Carcinogenicity Tests; D017277:Drug Approval; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000633:toxicity*; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D012306:Risk
D000960:Hypolipidemic Agents