The large administrative databases of health plans contain information on
drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of
drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged >or=18 years who received >or=2 prescriptions for
lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3-methylglutaryl
coenzyme A (
HMG-CoA) reductase inhibitors (
statins),
fibrates, extended-release
niacin,
cholesterol absorption inhibitors, or
statin combination
therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination
dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available
statins were similar, whereas the incidence of hospitalization for
muscle disorders increased 6.7-fold with
cerivastatin therapy. Patients who received a
lipid-lowering medication with a concomitant
cytochrome P450 3A4 (
CYP3A4) inhibitor had a 6-fold increased rate of
muscle disorders, including
rhabdomyolysis.
Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with
diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the
lipid-lowering
drug.
Statin monotherapy as currently prescribed is generally well tolerated and safe.