Statins and Liver Toxicity: A Meta‐Analysis

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Abstract
Study Objective. To assess the risk of liver function test (LFT) abnormalities with the use of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) for the treatment of hyperlipidemia. Design. Meta‐analysis of randomized, placebo‐controlled trials of statins used for the treatment of hyperlipidemia or for primary or secondary prevention of cardiovascular disease. Setting. University research center. Patients. A total of 49,275 patients from 13 trials. Intervention. A literature search of published clinical trials was performed in MEDLINE (January 1966–March 2003) and the Cochrane Controlled Trials Registry (first quarter 2003). Studies also were identified from the references of the trials and of published systematic reviews. Measurements and Main Results. For a trial to be included in the meta‐analysis, its duration of follow‐up had to be at least 48 weeks and the trial had to include at least 400 patients, with at least 200 treated with a statin. Trials conducted in transplant recipients were excluded. The proportion of patients having LFT abnormalities was low in both groups (statins 1.14% vs placebo 1.05%, odds ratio [OR] 1.26, 95% confidence interval [CI] 0.99–1.62, p=0.07). Only fluvastatin was associated with a significant increase in the odds of having LFT abnormalities (fluvastatin 1.13% vs placebo 0.29%, OR 3.54, 95% CI 1.1–11.6, p=0.04) compared with placebo, although this finding was based on only two trials. Conclusions. Our results support previous observations that pravastatin, lovastatin, and simvastatin at low‐to‐moderate doses are not associated with a significant risk of LFT abnormalities. Additional data are required to determine whether other statins have a similar safety profile.