Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study with 19-Year Follow-up

Document Type

Journal Article

Publication Date



Arthritis care & research




OBJECTIVE: Recent evidence suggest that hydroxychloroquine use is not associated with higher one-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8852 Veterans (mean age, 64±12 years, 14% women, 28% African Americans) with newly-diagnosed RA, in which 4426 patients initiated on hydroxychloroquine and 4426 initiated on another non-biologic disease-modifying antirheumatic drug (DMARD) were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in hydroxychloroquine and other DMARD groups, respectively, during first two years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS in hydroxychloroquine group (number needed to harm, 403; 95% CI, 217-1740) and 181% greater relative risk (95% CI, 11%-613%; p=0.030). Although overall 10-year risk remained significant (hazard ratio, 2.17; 95% CI, 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and one over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter which became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.