Simvastatin-related myopathy in shift workers: A report of two cases

Simvastatin is a widely used drug for dyslipidemia treatment, and the best therapeutic effects are achieved at night time. Simvastatin administration has been associated with the development of myopathy. Some polymorphisms in genes that are involved in the metabolism and transport of simvastatin seem to have an important role in the development of simvastatin-associated myopathy. The administration of 40 mg of simvastatin to 19 hyperlipidemic subjects with regular sleep rhythms (RR) and shift workers (SW) with predominant evening rhythms and sleep-wake disturbances, uncovered two SW volunteers who developed myopathy. We report two SWs who developed simvastatin-dependent myopathy after three weeks of treatment. The SLCO1B1 521T>C major risk allele was observed in one myopathy-affected and one unaffected subjects, the second affected patient shared polymorphisms with the unaffected subjects. The lack of consonance in the studied genotypes between SWs affected with simvastatin-associated myopathy can be related to circadian misalignment. Hence, other genes with circadian behavior and induced by simvastatin should be evaluated in future studies.