New York—Hydroxychloroquine, when used in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), doesn’t appear to cause any significant differences in QTc length or prolonged QTc, key measures of heart rate.

That’s according to new research presented at ACR Convergence, the American College of Rheumatology’s annual meeting. Hydroxychloroquine is commonly used to treat SLE, and many RA patients take the drug either alone or in combination with other treatments.

Columbia University–led researchers point out, however, that concerns have been raised about the drug’s possible heart-related side effects: the prolongation of QTc, or the time span the heart takes to contract and relax, and the development of arrhythmia (irregular heartbeats). The new study sought to assess QTc lengths in patients with RA and SLE and its association with hydroxychloroquine use.

“Hydroxychloroquine remains the foundation of disease-modifying antirheumatic drug therapy in rheumatic disease patients. Given recent concerns surrounding hydroxychloroquine’s use in COVID-19 patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms in a large, asymptomatic cohort of RA and SLE patients,” says study coauthor Elizabeth Park, MD, rheumatology fellow at Columbia University Irving Medical Center.

Researchers analyzed the cases of 681 SLE and RA patients without clinical cardiovascular disease (CVD). Of the participants, 307 came from two prospective RA cohorts with EKGs, and 374 came from a retrospective SLE cohort with EKGs performed as part of standard of care; all were recruited from tertiary referral centers.

Researchers explored the association between QTc length and HCQ use in regression models and adjusted for disease-specific characteristics and CVD risk factors.  

The majority, 54%, of the entire cohort were HCQ users, and 44% had a QTc greater than 440 milliseconds (ms). The mean QTc length was 437± 28 ms.

Results indicate that, overall, adjusted QTc length in HCQ users was comparable to that of non-HCQ users. Furthermore, multivariate logistic modeling demonstrated that HCQ use was not a significant predictor of prolonged QTc >440 or >500 ms for the entire cohort (OR 0.89; CI, 0.25-3.2, & OR 0.11; CI, 0.007-1.7, respectively), nor for the RA cohort (OR 1.1; CI, 0.54-2.2, & OR 0.80; CI, 0.23-2.8, respectively). In addition, HCQ use was not a significant predictor of a QTc >440 ms in the SLE subset (OR 2.0; CI, 0.46-8.8).

The authors add that nine out of 11 SLE patients with a QTc >500 ms were on HCQ, but the observations were too small to detect statistically significant differences between the HCQ groups, advising,

“Importantly, QTc >500 ms was not associated with arrhythmias or deaths.”
The study also notes that no significant interactions were found between HCQ use and other QTc-prolonging medications in the overall cohort and that use of HCQ combined with any QTc-prolonging medication was associated with a comparable QTc length (434 ms; CI, 430-439) versus use of HCQ alone (433 ms; CI, 429-437). On the other hand, the authors advise, a significant interaction (P = 0.014) was found between HCQ use and antipsychotic use in the SLE cohort, with QTc length being longer (441 ms; CI, 428-454) for those on both versus those only on HCQ (432 ms; CI, 428-436).

“This study demonstrates that in a large, combined cohort of SLE and RA patients, QTc length does not significantly differ in HCQ users compared with non-HCQ users even while adjusting for potential clinical confounders,” the researchers conclude. “Importantly, HCQ use was not associated with a prolonged QTc (>440 ms) in the combined and individual SLE and RA cohorts, nor was HCQ use a significant predictor of QTc length.”

“Overall, the use of hydroxychloroquine did not predict QTc length, even while adjusting for critical confounding factors, namely the use of other QTc-prolonging medications,” Dr. Park said. “Our findings reinforce the fact that hydroxychloroquine remains a safe, effective long-term disease-modifying drug for our rheumatic disease patients.”

The study does not mean the drug is necessarily safe—it has been repeatedly proven ineffective—for treating patients with novel coronavirus; however, the authors write. “It’s important to remember that COVID-19 patients who received hydroxychloroquine were likely critically ill,” according to Dr. Park. “Therefore, the effect of COVID-19 itself on the heart and subsequent arrhythmia must be considered. They also likely concurrently received azithromycin, another QTc-prolonging medication. Our next steps are to stratify data by length and cumulative dose of hydroxychloroquine therapy and analyze the associations with QTc length.”

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