Statin Use and the Risk of Graves' Orbitopathy: A Nationwide Population-Based Cohort Study

Background: Statin use is reported to reduce the risk of Graves' orbitopathy (GO) in Western populations. However, study regarding the protective effect of statins against GO in Asians with Graves' disease (GD) is scarce. This study aims to investigate the efficacy of statins in preventing GO in Asian GD patients. Materials and Methods: This nationwide, population-based retrospective cohort study used data from beneficiaries aged >40 years diagnosed with GD from the National Health Insurance Research Database (NHIRD) from 2010 to 2020. The International Classification of Diseases codes, Anatomical Therapeutic Chemical codes, and the surgery/procedure codes derived from the NHIRD were used to obtain the information on GD, GO, and statin use. Propensity score (PS) analysis with matching and inverse probability of treatment weighting analysis (IPTW) was conducted to minimize confounding. The Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to compare the risk of GO among statin users and nonusers. Results: The final analysis included 102,858 patients; 7,073 were statin users (62.9 +/- 10.6 years, 29.7% male), and 95,785 were nonusers (53.6 +/- 10.4 years, 25.7% male). The crude incidence rate of GO among statin users and nonusers was 5.00 parts per thousand versus 6.75 parts per thousand and 4.91 parts per thousand versus 5.15 parts per thousand for the overall population and population after PS matching method, respectively. The Cox regression analysis showed that statin users had a significantly lower risk of GO (adjusted hazard ratio [HR] after PS matching 0.79, 95% confidence interval [CI]: 0.63-0.99, p = 0.037; adjusted HR after IPTW method: 0.64, CI: 0.51-0.79, p < 0.001). The risk of GO was not different among users of different kinds of statins (i.e., atorvastatin, rosuvastatin, pitavastatin, and other statins) or among different intensities of statins (low-to-moderate intensity vs. high intensity). Conclusions: The use of statins in Asian GD patients was associated with a reduced risk of GO. In addition, the risk of developing GO among users of commonly prescribed statins or users of different intensities of statins was not significantly different.