3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors and the Risk of Cancer

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Abstract
NEWMAN and Hulley1 reviewed the findings on rodent carcinogenicity of lipid-lowering drugs and concluded that fibrates and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors initiate or promote cancer in rodents. In some cases, the levels of exposure were similar to those prescribed to humans. In humans, the relation between low cholesterol levels and cancer is the object of intense debate and justifiable preoccupation. Although cohort studies2,3 have demonstrated that low cholesterol levels are associated with more cancer deaths, the evidence for causality is weak, since preexisting cancer and other confounding variables might be responsible for the association. Evidence from clinical trials of lipid-modifying therapies is reassuring but not conclusive. Law et al4,5 published a meta-analysis of randomized controlled trials. They reported an odds ratio for cancer death of 1.07 (95% confidence interval [CI], 0.90-1.26). In an overview of randomized trials testing HMG-CoA reductase inhibitors, Hebert et al6 found no significant increase in the incidence of cancer (risk ratio, 1.03; 95% CI, 0.90-1.17).