Statins and liver toxicity: a meta-analysis.
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.


METHODS
Meta-analysis of randomized, placebo-controlled trials of statins used for the treatment of hyperlipidemia or for primary or secondary prevention of cardiovascular disease.


METHODS
University research center.


METHODS
A total of 49,275 patients from 13 trials.


METHODS
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.


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.
de Denus
Simon
S
Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, PA 19103-4495, USA.
Spinler
Sarah A
SA
Miller
Kristin
K
Peterson
Andrew M
AM
D000368:Aged; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy*; D008107:Liver Diseases / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors