Document Detail

Atorvastatin metabolite measurements as a diagnostic tool for statin-induced myopathy.
MedLine Citation:
PMID:  21815705     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Myopathic complaints are common in the general population and are more frequent with increasing age. When myopathic symptoms arise in a patient treated with a HMG-CoA reductase inhibitor (statin), it is always a question of whether the symptoms are due to statin-induced myopathy (SIM) or not (non-SIM). Diagnosis of SIM is not as straightforward as previously thought, because the most commonly used biomarker, serum creatine kinase, shows low specificity and selectivity, except in serious cases of rhabdomyolysis. There is a definite need for a novel biomarker for SIM.
OBJECTIVE: Based on a previous study reporting an altered metabolic profile with increased systemic exposure to the suspected muscle-toxic metabolite atorvastatin lactone in patients with SIM compared with healthy controls, this study aimed to explore the use of atorvastatin metabolite measurements to diagnose muscular complaints during statin treatment as being either SIM or non-SIM. PATIENTS, SETTING, AND STUDY DESIGN: Fifty-three patients with self-reported myopathic symptoms during atorvastatin treatment were recruited from our outpatient clinic. The symptoms were clinically evaluated as being SIM or non-SIM, on the basis of atorvastatin re-challenge testing. Atorvastatin and its metabolites were measured at steady state in all patients and compared with the clinical evaluation to see if this could predict the outcome and hence be suitable as a diagnostic tool for SIM.
MAIN OUTCOME MEASURE: This was an exploratory study to investigate the proportion of patients correctly diagnosed by different metabolite cut-off ratios.
RESULTS: With a cut-off ratio set at 1.1 for the atorvastatin lactone to atorvastatin acid ratio, 15 of 28 SIM patients (sensitivity of 54%) and 20 of 24 non-SIM patients (specificity of 83%) were correctly diagnosed. This corresponds to a positive predictive value of 79% and a negative predictive value of 61% (p = 0.006).
CONCLUSION: The present study confirms an altered metabolic pattern of atorvastatin in patients with SIM and substantiates a central role of the lactone forms of statins in future investigations of statin myotoxicity. The atorvastatin lactone to acid ratio seems to be a valuable supportive diagnostic tool with high specificity and moderate sensitivity, adding to ordinary clinical evaluations when diagnosing SIM.
Ine B Skottheim; Martin P Bogsrud; Monica Hermann; Kjetil Retterstøl; Anders Åsberg
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Molecular diagnosis & therapy     Volume:  15     ISSN:  1179-2000     ISO Abbreviation:  Mol Diagn Ther     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-09-14     Completed Date:  2012-02-15     Revised Date:  2013-05-16    
Medline Journal Info:
Nlm Unique ID:  101264260     Medline TA:  Mol Diagn Ther     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  221-7     Citation Subset:  IM    
School of Pharmacy, University of Oslo, Oslo, Norway.
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MeSH Terms
Biological Markers / blood
Creatine Kinase / blood
Heptanoic Acids / adverse effects*,  metabolism*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*,  metabolism*
Middle Aged
Muscular Diseases / chemically induced*,  diagnosis,  epidemiology
Pyrroles / adverse effects*,  metabolism*
Rhabdomyolysis / chemically induced,  diagnosis,  epidemiology
Sensitivity and Specificity
Reg. No./Substance:
0/Biological Markers; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; A0JWA85V8F/atorvastatin; EC Kinase

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