An analysis of 681 patients with rheumatoid arthritis and systemic lupus erythematosus revealed that hydroxychloroquine use is not associated with QTc length prolongation, even when given in combination with other QTc-prolonging medications.

Hydroxychloroquine (HCQ) plays an essential role in both systemic lupus erythematosus (SLE) and in the management of rheumatoid arthritis (RA), both as monotherapy and combined with other disease modifying antirheumatic drugs (DMARDs). However, there was an ongoing concern regarding its cardiovascular safety. Recently, the interest increased because of an observational study of COVID-19 patients reporting that 19% of those receiving HCQ demonstrated a QTc >500 ms, including 1 torsades de pointes tachycardia [2]. “Given recent concerns surrounding HCQ use in COVID-19 patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms (ECGs) in a large, asymptomatic cohort of RA and SLE patients,” said study co-author Dr Elizabeth Park (Columbia University Irving Medical Center, USA).

For this purpose, the researchers assessed QTc length and its association with HCQ use in a large SLE and RA cohort. The cross-sectional study analysed data of 681 RA and SLE patients without clinical cardiovascular disease, including 2 prospective RA cohorts of 307 patients and a retrospective SLE cohort of 374 patients. In the 2 prospective RA cohorts, ECGs were performed as part of study data collection, while in 1 retrospective SLE cohort (n=374) ECGs were performed as part of standard-of-care. The researchers explored the association between QTc length and HCQ use by these patients, and they adjusted the data for disease-specific characteristics and cardiovascular disease risk factors.

Of the whole study group (RA and SLE), 54% used HCQ and 44% had QTc lengths of more than 440 ms. The mean QTc length was 437 ± 28 ms. However, in the entire cohort, adjusted QTc length among HCQ users was comparable to those who did not use the drug. In multivariate logistic modelling, HCQ use was not a significant predictor of prolonged QTc. This was true both for the RA and the SLE cohort. However, 9 out of 11 of the SLE patients who did have a prolonged QTc were taking HCQ. Yet, these observations were too small to detect statistically significant differences between the HCQ groups.

The study also did not find any significant interactions between HCQ and other QTc-prolonging drugs in the patients. HCQ use combined with other QTc-prolonging medications resulted in a comparable QTc interval to HCQ alone. In the SLE group, HCQ combined with anti-psychotic drugs did result in longer QTc compared with using HCQ alone (441 ms vs 432 ms; P=0.014).

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

The different results seen in COVID-19 patients might be explained by the fact that these patients were critically ill. Therefore, the effect of COVID-19 itself on the heart and subsequent arrhythmia must be considered.

  1. Park E. Hydroxychloroquine use was not associated with QTc length in a large cohort of SLE and RA patients. Abstract 0431, ACR Convergence 2020 Virtual Annual Meeting, 5-9. November 2020.
  2. Mercuro NJ, et al. JAMA Cardiol. 2020;5:1036-1041.