Hydroxychloroquine not associated with prolonged heart rhythm intervals in RA, lupus
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Treatment with hydroxychloroquine does not impact corrected QT length among patients with rheumatoid arthritis or systemic lupus erythematosus, even after adjusting for confounders, according to a speaker at ACR Convergence.
“Hydroxychloroquine is a cornerstone of treatment for lupus and patients with rheumatoid arthritis,” Elizabeth Park, MD, a rheumatology fellow at the Columbia University Irving Medical Center, told attendees at a virtual press conference. “Many also take this drug either alone or in combination with other treatments. With long-term use, the metabolites from hydroxychloroquine can actually build up in different tissues, such as the skin, within the eyes and the heart. The most life-threatening issues concern the heart, specifically the prolongation of the QT interval, or the timespan the heart takes to contract and relax, and the subsequent development of arrhythmias, or irregular heartbeats.”
“There have also been escalating concerns regarding cardiac arrhythmia in COVID-19 patients who were treated with hydroxychloroquine, with one study citing up to 19% of those patients who received hydroxychloroquine demonstrating a QT interval that was greater than 500 milliseconds, with one report of torsades de pointes, a potentially fatal arrhythmia,” she added. “Currently, there are no clear guidelines or recommendations for whether rheumatic patients who are receiving hydroxychloroquine long-term should be screened somehow with an EKG or other means.”
To assess the link between hydroxychloroquine treatment with corrected QT (QTc) length among patients with SLE and RA, Park and colleagues analyzed data from two prospective RA cohorts with EKGs, as part of a study data collection, and one retrospective SLE cohort with EKGs performed as part of standard of care. In all, the researchers studied data from 618 patients, including 307 from the RA cohorts and 374 from the SLE cohort. Among the entire study population, 54% were using hydroxychloroquine.
All participants were recruited from tertiary referral centers. The researchers examined associations between QTc length and hydroxychloroquine using regression models, adjusting for disease-specific characteristics and cardiovascular disease risk factors.
According to the researchers, 44% of the entire study cohort demonstrated a QTc of more than 440 milliseconds, and the mean QTc length was 437± 28 milliseconds. Adjusted QTc length among those treated with hydroxychloroquine in the entire cohort was comparable to that of non-users. Also in the entire cohort, in multivariate logistic modeling, the use of hydroxychloroquine was not a significant predictor of a prolonged QTc of more than 440 milliseconds (OR = 0.89; 95% CI, 0.25-3.2), or more than 500 milliseconds (OR = 0.11; 95% CI, 0.007-1.7).
Hydroxychloroquine was similarly not a predictor of a prolonged QTc of more than 440 milliseconds (OR = 1.1; 95% CI, 0.54-2.2), or more than 500 milliseconds (OR = 0.80; 95% CI, 0.23-2.8) in just the RA cohort. Its use was also unable to predict a QTc of more than 440 milliseconds in the SLE subset (OR = 2; 95% 95% CI, 0.46-8.8). However, nine out of 11 participants with SLE who demonstrated a QTc of more than 500 milliseconds were treated with hydroxychloroquine. Still, these observations were too small to detect statistically significant differences between the hydroxychloroquine groups, the researchers wrote.
In addition, a QTc length of 500 milliseconds was not associated with arrhythmias or deaths. There were also no significant interactions between hydroxychloroquine use and other QTc prolonging medications in the entire cohort. The researchers found that hydroxychloroquine, when combined with any QTc-prolonging medication, was associated with a comparable QTc length (434 milliseconds; 95% CI, 430-439), compared with hydroxychloroquine alone (433 milliseconds; 95% CI, 429-437).
However, Park and colleagues did observe a significant interaction between the use of hydroxychloroquine and antipsychotic use among the SLE cohort (P = .014), with QTc length being longer (441 milliseconds; 95% CI, 428-454) among receiving n both compared those using hydroxychloroquine only (432 milliseconds; 95% CI, 428-436).
“Overall, the use of hydroxychloroquine did not predict QTc length, even while we adjusted for critical other factors, namely the use of other QTc-prolonging medications,” Park said. “So, our findings really do reinforce the fact that hydroxychloroquine is a safe and effective long-term disease modifying drug for our rheumatic patients. I think it is important to remember that COVID-19 patients who receive hydroxychloroquine were likely to be critically ill, so we have to consider the effects of COVID-19 itself on the heart, as well as the potential to develop arrhythmia from that.”
“In addition, many of these patients also concurrently received azithromycin, which is known to prolong the QT interval,”she added. “So, whatever conflicting or negative conclusions about the efficacy of hydroxychloroquine in COVID-19 patients cannot be directly applied to our rheumatic patients.”
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Park E. Abstract 0431. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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