Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.
OBJECTIVE
Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association.


METHODS
After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events.


RESULTS
Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level.


CONCLUSIONS
Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.
Center for Development of Integrative Education in Pharmacy and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Toshiyuki
T
Sakaeda
Kaori
K
Kadoyama
Yasushi
Y
Okuno
D022126:Access to Information; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D003404:Creatinine / Q000097:blood; D057225:Data Mining / Q000379:methods*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009132:Muscles / Q000187:drug effects*; D051437:Renal Insufficiency / Q000139:chemically induced; D014481:United States; D014486:United States Food and Drug Administration
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003404:Creatinine