Heart rhythm not significantly affected by hydroxychloroquine in lupus
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Corrected QT interval was unaffected by hydroxychloroquine use in patients with systemic lupus erythematosus — both with and without chronic kidney disease, according to data presented at the ACR Convergence 2020 virtual meeting.
These findings are in line with current standard of care, which does not require baseline or serial monitoring with EKG in patients with SLE prescribed hydroxychloroquine, according to study co-author H. Michael Belmont, MD, professor of medicine at the New York University Grossman School of Medicine and co-director of the NYU Lupus Center.
The off-label use of hydroxychloroquine increased during the COVID-19 pandemic, and concerns were raised regarding the drug’s potential effects on cardiac toxicity. “The predicate for this study was to determine whether we could reassure both prescribing providers and patients that this drug is effective and safe,” Belmont said during a press conference.
Belmont and colleagues retrospectively reviewed data from the EPIC EMR system at NYU Langone Health for 194 patients with systemic lupus erythematosus between March 12, 2012, and May 1, 2020. Data collected included EKG, corrected QT interval (QTc) on first and last EKG, creatinine and demographics. Prolonged QTc was defined as > 450 ms in men and >470 ms in women, and severe QTc prolongation was defined as > 500 ms. The researchers defined chronic kidney disease as eGFR < 60 mL/min.
Nearly half of the patients had one EKG (n = 90), of whom 91% were female, 32.2% Black, 38.8% white, 20% Hispanic, 6.6% Asian and 2.2% other. Of these, 75 patients were taking hydroxychloroquine and the remaining 15 were not.
According to EKG data, eight patients taking hydroxychloroquine (10.6%) had prolonged QTc vs. one patient in the no hydroxychloroquine group (6.6%). Hydroxychloroquine use was not associated with a significant difference in mean QTc interval (P = .586). Twenty-three patients in the cohort had chronic kidney disease, among whom QTc was prolonged in four of 19 patients taking hydroxychloroquine (21%) and zero of four patients not taking the antimalarial. Again, hydroxychloroquine use was not associated with a significant difference in mean QTc interval (P = .784). Additionally, neither tachyarrthymia nor Torsades de pointes (Tdp) were documented.
“I think it’s important for the public and press to understand that this drug is not new, novel — it’s not a flash in the pan,” he said.
Belmont explained the history of the drug, which began when indigenous peoples of what is now Peru used the bark of the Cinchona tree to treat febrile patients, likely due to mosquito-borne malaria. In the 1500s, Jesuit missionaries brought seedlings back to Europe, and the first drug was isolated from the bark – quinine – in 1820. Hydroxychloroquine became available in 1946, and in 1951, a study in The Lancet described the benefit of hydroxychloroquine in the treatment of lupus.
“There’s an absence of evidence for serious clinical consequences of any effect of this drug on QTc interval; it matches the general clinical observation that we don’t see Tdp in lupus patients on hydroxychloroquine,” Belmont said. “The few case reports of this association have generally been in patients who purposely or inadvertently had overdoses of the drug. [Our findings are] Also in support of current standard of care that we do not do baseline EKGs or serial EKGs over time to measure the QTc interval.”
Belmont noted limitations of the study — patients with known underlying heart disease were not included, and the researchers did not account for the potential confounding effect of the concurrent use of drugs that are known to effect the QTc interval, such as azithromycin.
“We propose that going forward, there would be value to further reassure both our patients and prescribers seeking to get maximum adherence with the use of this disease-modifying drug by doing a prospective trial where we’d measure the QTc at baseline and after exposure to the drug,” Belmont said.
He also pointed out the well-known issue of the prescribed amount of hydroxychloroquine not associating with the blood levels of the drug, which Belmont said is likely explained by patient adherence.
“We also propose to measure QTc intervals and associate it with hydroxychloroquine blood levels. ... If there was to be a concern that this drug effects the repolarization of the ventricle and the QTc interval, placing our patients at risk for serious cardiac arrythmias, we might anticipate a dose response curve and that would be lower hydroxychloroquine blood levels as compared to higher blood hydroxychloroquine levels, there would be lower vs. higher QTc intervals,” he said.
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Haj-Ali M. Abstract #1844. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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