Early Statin Use Following Diagnosis of Graves’ Disease Is Associated with a Reduced Risk of Moderate-to-Severe Graves’ Orbitopathy in Middle-Aged Adults: Evidence from a Nationwide Taiwanese Cohort

<b><i>Background:</i></b> Statin use is associated with a reduced risk of Graves' orbitopathy (GO). However, whether the timing of initiating statin treatment after the diagnosis of Graves' disease (GD) affects the association between statin and GO risk remains unclear. This study aims to evaluate the risk of GO based on varying intervals of statin initiation following GD diagnosis. <b><i>Materials and Methods:</i></b> This nationwide, population-based retrospective cohort study used data of all beneficiaries aged >40 years diagnosed with GD from Taiwan's National Health Insurance Research Database (2009-2019). We excluded patients with incomplete data, follow-up <6 months, with a diagnosis of GO, or on medication for hyperlipidemia before GD diagnosis. We performed 1:4 matching based on age, sex, and the duration between GD diagnosis and the index day for statin users and nonusers. GO patients were further classified as having mild or moderate-to-severe GO according to the type of treatment received. <b><i>Results:</i></b> A total of 47,424 patients were categorized into Group A (<1 year, 4649 statin users; 18,584 nonusers), Group B (1-2 years, 3060 statin users; 12,349 nonusers), and Group C (2-3 years, 1752 statin users; 7030 nonusers) by the duration between GD diagnosis and the index date. Cox regression showed that statin users in Group A had a significantly lower risk of total GO (adjusted hazard ratio [HR]: 0.66, confidence interval [CI]: 0.47-0.94, <i>p</i> = 0.023) and moderate-to-severe GO (adjusted HR: 0.39, CI: 0.19-0.80, <i>p</i> = 0.010), but not mild GO (adjusted HR: 0.84, CI: 0.56-1.25, <i>p</i> = 0.385) than nonusers. However, no significant associations were found in Groups B and C. The risk of GO was not statistically different among users of various types or intensities of statins in any group. <b><i>Conclusion:</i></b> Initiating statin treatment within one year after being diagnosed with GD was associated with 34% and 61% reduction in total and moderate-to-severe GO risk, respectively. For patients whose treatment was initiated more than one year after GD was diagnosed, statin use was not related to the risk of total, mild, and moderate-to-severe GO. These findings suggest that the timing of statin initiation may influence the risk of GO, which warrants further confirmation through prospective studies.