Risk factors for rhabdomyolysis with HMG-CoA reductase inhibitors identified using a postmarketing surveillance database in Japan

Objective: To investigate quantitatively the risk factors for rhabdomyolysis or related symptoms associated with HMG-CoA reductase inhibitors (statins), we used the lipid-lowering drug database (32,157 patients) developed by the RAD-AR Council, Japan, based on the postmarketing surveillance (PMS) data of pharmaceutical companies to perform a nested case-control study. Materials and methods: Of 26,849 patients taking statins, the case group was composed of 51 patients who experienced rhabdomyolysis or related symptoms while taking statins, and the control group was 1,020 patients randomly selected from patients who did not experience rhabdomyolysis or related symptoms while taking statins. Relevant factors that can be extracted from the database were: sex, age, body mass index (BMI), statin use duration, complications, concomitant medication, and clinical laboratory test values. Results: Among those taking statins, 51 experienced rhabdomyolysis or related symptoms. Factors differing significantly between the two groups by univariate analysis were age, duration of statin intake, combination drugs (Ca antagonists, angiotensin II receptor blocker (ARB), cardiac drugs, benzodiazepines, mucoprotective drugs, insulin, α-glucosidase inhibitors), clinical laboratory results (high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase, alkaline phosphatase, total bilirubin), and complications (alcoholic hepatitis). Conditional multivariate logistic analysis of these factors yielded adjusted/odds ratios of 8.82 for the concomitant administration of an ARB and 3.45 for increased AST and 3.20 for increased total bilirubin levels. Conclusion: Risk factors for rhabdomyolysis or related symptoms associated with taking statins were combination with ARB and increases in AST or total bilirubin levels.