Sjögren’s syndrome (SS) is a chronic systemic inflammation disease with clinical presentation of dry eye, dry mouth, and polyarthralgia. Active inflammation is associated with an increased risk of associated arterial stiffness or subclinical atherosclerosis-related cardiovascular events. We used the longitudinal health insurance database of Taiwan, which includes one million participants, to evaluate the relationship between the clinical medication of hydroxychloroquine (HCQ) and the development of coronary artery disease (CAD). In total, 1674 patients with SS receiving HCQ medication were included after exclusion for previous CAD. Altogether, 1142 SS patients were included for evaluation after follow-up for more than one year. After adjusting for age, gender, medications, and chronic comorbidities, a significantly decreased hazard ratio (HR) for developing CAD was found among SS patients with higher medication possession ratio (MPR) of HCQ (HR = 0.49, 95% confidence interval, CI: 0.26–0.94) when compared with low MPR of HCQ. A low HR for CAD was observed in SS patients with a high cumulative dose of at least 100,267 mg of HCQ (HR = 0.25, 95% CI: 0.09–0.66). Long-term HCQ therapy may decrease the HR of CAD in SS patients. The significant cardiovascular protective effect of HCQ therapy was observed in our study.
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