Statin Myopathy

Abstract

The spectrum of statin-induced myopathy includes myalgias and weakness, with or without CK elevation, and in its most severe form rhabdomyolysis with renal failure. Myalgias are not uncommon, occurring in about 10% of statin users, but myopathy with CK elevation is much rarer (~0.5%). The risk for myopathy is substantially increased when concomitant medication is taken that interferes with the cytochrome P450 (CYP3A4) detoxification system. In those cases, pravastatin, fluvastatin or rosuvastatin, which undergo metabolism by a different route, should be chosen. Other risk factors are certain patient characteristics (age, systemic illness, underlying neuromuscular disorder, vitamin D-deficiency, genetic variants of hepatic drug transporters) or drug characteristics (type and dose of statin, co-medication). Pathogenesis of statin myopathy is complex and involves the mevalonate metabolic pathway, direct effects on mitochondria and indirect pro-apoptotic effects, but also immune mechanisms (autoantibodies against HMG-CoA reductase, necrotizing myopathy). The management of statin-induced myopathy is straightforward in many cases, simply discontinuing the responsible agent. Re-administration of the statin is possible in half the cases using a lower dose and/or a different statin with less intrinsic myotoxicity. Alternative diagnoses (other neuromuscular disorders or autoimmune-necrotizing myopathy) have to be considered, if symptoms or CK elevations persist for more than 6 months after cessation of statin therapy. An algorithm for the management of these patients is presented.