No Increased Risk for Adverse Cardiovascular Events or Death With Hydroxychloroquine in Veterans With RA

doctor speaks with veteran patient
Researchers evaluated the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis before the COVID-19 pandemic.

In veterans with newly diagnosed rheumatoid arthritis (RA), the incidence of long QT syndrome (LQTS) and arrhythmia-related hospitalization was low during the first 12 months after initiation of hydroxychloroquine (HCQ) therapy or another nonbiologic disease-modifying antirheumatic drug (DMARD), according to study results published in Arthritis & Rheumatology. In addition, no adverse cardiovascular events or death were observed in association with HCQ therapy.

In early 2020, HCQ was briefly authorized to treat COVID-19. During that time, case reports described incidents of prolonged QT interval with HCQ use. Although HCQ authorization was revoked for use in patients with COVID-19, HCQ remains a common treatment for RA. However, more information is needed on its cardiovascular safety.

Using the Department of Veterans Affairs database, researchers conducted an active comparator safety study in which they identified veterans newly diagnosed with RA between October 2001 and December 2017. Researchers used propensity scores to match patients who were initiated on HCQ therapy with those who were initiated on another nonbiologic DMARD. Patients were followed up with for 12 months.

Primary study outcomes were incident LQTS, arrhythmia-related hospitalization, and all-cause mortality.

A total of 8852 patients (mean age, 64±12 years; 14% women; 28% Black) were included in the analysis. Propensity-score matching resulted in a balanced distribution in 87 baseline characteristics (absolute standardized differences of <4%) between the 4426 matched pairs.

Overall, LQTS events occurred in 3 (0.03%) of the total cohort of which 2 were in the HCQ group. There were 56 (0.63%) arrhythmia-related hospitalizations; 30 in the HCQ group (hazard ratio [HR] associated with HCQ initiation, 1.16; 95% CI, 0.68-1.95). All-cause mortality occurred in 144 (3.25%) of patients in the HCQ group and in 136 (3.07%) patients in the non-HCQ group (HR associated with HCQ, 1.06; 95% CI, 0.84-1.34). During the first 30 days, there were no LQTS events, 2 arrhythmia-related hospitalizations in the DMARD group, and 13 deaths (6 in the HCQ group).

Limitations of the study included its observational study design, potential misclassification or underestimation of QT prolongation due to lack of access to electrocardiograms, and lack of generalizability of the largely male cohort to the general population of patients with RA.

“To the best of our knowledge, this is the largest observational comparative safety study of HCQ initiation in a propensity score-matched balanced cohort of patients with RA that provides new information about the cardiovascular safety of HCQ,” the researchers noted.

They concluded, “Although the very low incidence of LQTS in our study is generally consistent with those reported in the literature, future studies need to replicate these findings with electrocardiographically adjudicated incident LQTS events.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the disclosures.


Faselis C, Zeng-Treitler Q, Cheng Y, et al. Cardiovascular safety of hydroxychloroquine in veterans with rheumatoid arthritis. Arthritis Rheumatol. Published online May 10, 2021. doi:10.1002/ART.41803