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Assessment of statin-associated muscle toxicity in Japan: a cohort study conducted using claims database and laboratory information
  1. Chia-Hsien Chang1,2,
  2. Makiko Kusama2,
  3. Shunsuke Ono2,
  4. Yuichi Sugiyama2,3,
  5. Takao Orii4,
  6. Manabu Akazawa5
  1. 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
  2. 2Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
  3. 3Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, RIKEN, Kanagawa, Japan
  4. 4Pharmacy Department, NTT Medical Center Tokyo, Tokyo, Japan
  5. 5Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
  1. Correspondence to Professor Manabu Akazawa; makazawa{at}


Objective To estimate the incidence of muscle toxicity in patients receiving statin therapy by examining study populations, drug exposure status and outcome definitions.

Design A retrospective cohort study.

Setting 16 medical facilities in Japan providing information on laboratory tests performed in and claims received by their facilities between 1 April 2004 and 31 December 2010.

Participants A database representing a cohort of 35 903 adult statin (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin) users was studied. Use of interacting drugs (fibrates, triazoles, macrolides, amiodarone and ciclosporin) by these patients was determined.

Main outcome measure Statin-associated muscle toxicity (the ‘event’) was identified based on a diagnosis of muscle-related disorders (myopathy or rhabdomyolysis) and/or abnormal elevation of creatine kinase (CK) concentrations. Events were excluded if the patients had CK elevation-related conditions other than muscle toxicity. Incidence rates for muscle toxicity were determined per 1000 person-years, with 95% CI determined by Poisson regression.

Results A total of 18 036 patients accounted for 42 193 person-years of statin therapy, and 43 events were identified. The incidence of muscle toxicity in the patients treated with statins was 1.02 (95% CI 0.76 to 1.37)/1000 person-years. The estimates varied when outcome definitions were modified from 0.09/1000 person-years, which met both diagnosis and CK 10× greater than the upper limit of normal range (ULN) criteria, to 2.06/1000 person-years, which met diagnosis or CK 5× ULN criterion. The incidence of muscle toxicity was also influenced by the statin therapies selected, but no significant differences were observed. Among 2430 patients (13.5%) received interacting drugs with statins, only three muscle toxicity cases were observed (incidence: 1.69/1000 person-years).

Conclusions This database study suggested that statin use is generally well tolerated and safe; however, the risk of muscle toxicity related to the use of interacting drugs requires further exploration.

  • statin
  • interacting drugs
  • muscle toxicity
  • claims database
  • Japan

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