Use of multiple international healthcare databases for the detection of rare drug-associated outcomes: A pharmacoepidemiological programme comparing rosuvastatin with other marketed statins

Background: Statins (inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase) are associated with rare but serious adverse events involving the muscle, kidney and liver. To compare the safety profile of rosuvastatin with other marketed statins, four pharmacoepidemiological studies were conducted using different national healthcare databases. These studies used a coordinated methodology to facilitate future meta-analysis. Objective: To achieve enhanced estimates of rosuvastatin safety relative to other statins, by performing a meta-analysis of four rosuvastatin safety studies. Methods: Outcomes were identified using computerised codes, and validated using hospital records or questionnaires. Incidence estimates were based on current statin exposure. Incidence estimates for hospitalised myopathy, rhabdomyolysis, acute renal failure and acute liver injury among users of rosuvastatin and users of other statins were pooled across studies using a weighted average corresponding to the Mantel-Haenszel estimate of the common relative risk. Results: More than 29 900 person-years were accrued for rosuvastatin use and more than 166 900 person-years were accrued for other statin use. Relative to other statins, rosuvastatin was not associated with significant differences in the incidence of hospitalised myopathy (+0.5 cases per 10 000 person-years; 95%CI: -0.6 to 1.6), rhabdomyolysis (+0.7 cases per 10 000 person-years; 95%CI: -0.3 to 1.6), acute renal failure (-0.2 cases per 10 000 person-years; 95%CI: -2.9 to 2.5) or acute liver injury (-0.8 cases per 10 000 person-years; 95%CI: -1.8 to 0.2). Conclusion: In this large sample (~200 000 person-years), no significant difference in the risk of myopathy, rhabdomyolysis, acute liver injury or acute renal failure was seen between rosuvastatin and other statins.

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