1. Among a large, matched cohort of veterans with rheumatoid arthritis, initiation of hydroxychloroquine was not associated with a higher risk of adverse cardiovascular events or death.
Evidence Rating Level: 1 (Excellent)
In anecdotal case reports, hydroxychloroquine (HCQ) has been reported to prolong the QT interval, thus increasing the risk of arrhythmia and sudden cardiac death. This concern had been heightened in the recent past due to the brief, and now-revoked, authorization of HCQ for the treatment of COVID-19. Because HCQ is often used in the management of patients with rhematic diseases, this study sought to evaluate the safety of HCQ among veterans with rheumatoid arthritis (RA). A strategy that attempted to emulate the design of a randomized controlled trial was utilized, though ultimately the study was of a propensity score-matched cohort design. The primary outcomes were incident long QT syndrome (LQTS), arrhythmia-related hospitalization, and all-cause mortality. 4,426 veterans with RA treated with HCQ (mean [SD] age = 63.9 [12.0] years, 13.8% female) were matched with 4,426 veterans with RA treated with a disease-modifying antirheumatic drug (DMARD) other than HCQ (mean [SD] age = 63.9 [11.9] years, 14.2% female). There were found to be 3 LQTS events and 56 arrhythmia-related hospitalizations, of which 2 and 30, respectively, belonged to the HCQ cohort. Finally, all-cause mortality occurred in 144 and 136 veterans in the HCQ and non-HCQ cohorts, respectively (HR 1.16, 95% CI 0.68 to 1.95). In all, initiation of HCQ for the treatment of RA was found to be safe and not associated with increased all-cause mortality. Furthermore, this study demonstrates that the incidence of LQTS is extremely low, and not heightened by administration of HCQ, at least in this particular cohort.
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