Cardiovascular Safety of Hydroxychloroquine in Veterans with Rheumatoid Arthritis.

Faselis, Charles; Zeng-Treitler, Qing; Cheng, Yan; Kerr, Gail S; Nashel, David J; Liappis, Angelike P; Weintrob, Amy C; Karasik, Pamela E; Arundel, Cherinne; Boehm, Denise; Heimall, Michael S; Connell, Lawrence B; Taub, Daniel D; Shao, Yijun; Redd, Douglas F; Sheriff, Helen M; Zhang, Sijian; Fletcher, Ross D; Fonarow, Gregg C; Moore, Hans J; Ahmed, Ali

OBJECTIVE Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. We examined the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8852 Veterans newly diagnosed with RA between October 1, 2001, and December 31, 2017. Patients were initiated on HCQ (n=4426) or another non-biologic disease-modifying antirheumatic drug (DMARD; n=4426) after RA diagnosis, up to December 31, 2018, and followed for 12 months after therapy initiation, up to December 31, 2019. RESULTS Patients had a mean age of 64 (±12) years, 14% were women, 28% African American, and were balanced on 87 baseline characteristics. There were 3 (0.03%) long QT syndrome (LQTS) events, of which 2 belonged to the HCQ group. Of the 56 (0.63%) arrhythmia-related hospitalizations, 30 belonged to the HCQ group (hazard ratio associated with HCQ, 1.16; 95% CI, 0.68-1.95). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) patients in the HCQ and non-HCQ groups, respectively (hazard ratio associated with HCQ, 1.06; 95% CI, 0.84-1.34). During the first 30 days of follow-up, there was no LQTS event, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSIONS The incidence of LQTS and arrhythmia-related hospitalization was low in patients with RA during the first year after the initiation of HCQ or another non-biologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.