The risk for significant creatine kinase elevation with statins.
BACKGROUND
The HMG-CoA reductase inhibitors (statins) are effective for reducing long-term cardiovascular morbidity and mortality in both primary and secondary prevention. The most serious adverse reaction is significant elevation of creatine kinase (CK) leading to rhabdomyolysis. The incidence of CK elevation is low in randomized, controlled trials. The rate may be higher in 'real-world', less controlled settings. Data on the risks of statin-associated rhabdomyolysis in 'real-world' practice settings are limited.


OBJECTIVE
The aim of this study was to examine the risk for CK elevation among statin users in a clinical practice setting. Potential risk factors were identified and evaluated to quantify the risk for CK elevation with statins.


METHODS
This case-control study was conducted at Kaiser Permanente Colorado. Patients with prescriptions for lovastatin or simvastatin between 1 January 1999 and 30 June 2006 were identified. Cases (n = 183), i.e. patients with a CK > or =10x the upper limit of normal (ULN) while receiving a statin during this time period, were each matched on the date of statin purchase to ten control patients (n = 1830) without CK > or =10x ULN while receiving a statin. Multivariate, conditional logistic regression was used to assess the associations between the statin, statin dose, demographic, co-morbidity, laboratory, and medication factors potentially associated with CK >or =10x ULN.


RESULTS
he mean (SD) age of patients was 64.9 (11.5) years and 56.9% were male. Overall, simvastatin use was associated with a higher likelihood for CK > or =10x ULN than lovastatin (adjusted odds ratio [OR] 4.6; 95% CI 1.1, 12.4). Using simvastatin 40 mg daily as the referent, and in the absence of interacting medications, only simvastatin 80 mg was associated with a higher likelihood for CK > or =10x ULN (OR 2.7; 95% CI 1.1, 6.9). In the presence of interacting medications, all doses of simvastatin and only lovastatin 80 mg were associated with a higher likelihood for CK > or =10x ULN.


CONCLUSIONS
In this study, simvastatin was associated with a higher likelihood for CK > or =10x ULN than lovastatin. High-dose simvastatin, in particular, appears to confer a greater risk than lower doses of either simvastatin or lovastatin.
Stolcpart
Ryan S
RS
EPIC Systems Corporation, Madison, Wisconsin, USA.
Olson
Kari L
KL
Delate
Thomas
T
Rasmussen
Jon
J
Rehring
Thomas F
TF
Merenich
John A
JA
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012306:Risk
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003402:Creatine Kinase