CARCINOGENICITY OF LIPID-LOWERING DRUGS

Objective.-To review the findings and implications of studies of roden t carcinogenicity of lipid-lowering drugs. Data Sources.-Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Des k Reference (PDR), additional information obtained from the US Food an d Drug Administration, and published articles identified by computer s earching, bibliographies, and consultation with experts. Study Sample. -We tabulated rodent carcinogenicity data from the 1994 PDR for all dr ugs listed as ''hypolipidemics.'' For comparison, we selected a strati fied random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans. Data Synthesis.-All members of the two m ost popular classes of lipid-lowering drugs (the fibrates and the stat ins) cause cancer in rodents, in some cases at levels of animal exposu re close to those prescribed to humans. In contrast, few of the antihy pertensive drugs have been found to be carcinogenic in rodents. Eviden ce of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficien t duration of follow-up. Conclusions.-Extrapolation of this evidence o f carcinogenesis from rodents to humans is an uncertain process. Longe r-term clinical trials and careful postmarketing surveillance during t he next several decades are needed to determine whether cholesterol-lo wering drugs cause cancer in humans. In the meantime, the results of e xperiments in animals and humans suggest that lipid-lowering drug trea tment, especially with the fibrates and statins, should be avoided exc ept in patients at high short-term risk of coronary heart disease.