Variation in Association Between Thiazolidinediones and Heart Failure Across Ethnic Groups: Retrospective analysis of Large Healthcare Claims Databases in Six Countries

Introduction: The prevalence of polymorphisms among the metabolising enzymes and pharmacodynamic receptors relevant for the thiazolidinediones differs by ethnic group, a factor that may modify risk of adverse drug events. Objective: The aim of the study was to determine if the risk of oedema or heart failure associated with the thiazolidinediones varies in populations in Australia, Canada, Hong Kong, Japan, Korea and Taiwan. Methods: Sequence symmetry analyses were undertaken to investigate the risk of peripheral oedema, as measured by incident furosemide dispensing, and risk of hospitalisations for heart failure. Results were pooled, with Australia and Canada representing predominantly Caucasian population and all other countries contributing to Asian population estimates. Results: Pooled estimates of risk for furosemide initiation in the Caucasian populations were significantly increased for pioglitazone [adjusted sequence ratio (ASR) 1.47; 95 % confidence interval (CI) 1.14–1.91] and rosiglitazone (ASR 1.65; 95 % CI 1.58–1.72), while in the Asian populations, the pooled risk estimates were lower (ASR 1.11; 95 % CI 0.93–1.32 and ASR 1.21; 95 % CI 1.01–1.45 for pioglitazone and rosiglitazone, respectively). Results for hospitalisation for heart failure showed a similar trend, with elevated risk in the Australian data (ASR 1.88; 95 % CI 1.01–3.5 and ASR 1.25; 95 % CI 0.76–2.05 for pioglitazone and rosiglitazone, respectively), while no increased risk was found in the pooled results for the Asian populations. Conclusion: The risk of both oedema and heart failure with thiazolidinediones was higher in predominantly Caucasian countries than in the Asian countries assessed. Assessment of adverse events by ethnicity may support safer medicine use.