Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.
BACKGROUND
Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available.


OBJECTIVE
To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting.


METHODS
Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy.


METHODS
Incidence rates of rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis.


RESULTS
In 252,460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10,000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate.


CONCLUSIONS
Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.
Graham
David J
DJ
Office of of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Md 20857, USA. grahamd@cder.fda.gov
Staffa
Judy A
JA
Shatin
Deborah
D
Andrade
Susan E
SE
Schech
Stephanie D
SD
La Grenade
Lois
L
Gurwitz
Jerry H
JH
Chan
K Arnold
KA
Goodman
Michael J
MJ
Platt
Richard
R
D002995:Clofibric Acid / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D015994:Incidence; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000453:epidemiology*; D012306:Risk
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D002995:Clofibric Acid