Hydroxychloroquine prescribers 'should be vigilant' for potential cardiac toxicity
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Rheumatologists who prescribe hydroxychloroquine or chloroquine should be aware of their potential cardiac toxicity, especially in high-risk patients with rheumatic disease, according to an American College of Rheumatology white paper.
“We felt this article was important to address the knowledge and limitations in our knowledge of hydroxychloroquine (HCQ) and chloroquine (CQ) and the risk of potential adverse cardiovascular outcomes,” Julianna Desmarais, MD, of Oregon Health and Science University, in Portland, told Healio Rheumatology.
“While these medications already have FDA warnings for cardiac toxicity in the label, this isn’t necessarily common knowledge among prescribers of these medications,” she added. “The COVID-19 pandemic highlighted some of the complications with using HCQ in patients who already had risk for QT prolongation, and we wanted to provide a balanced review of what is known about this topic.”
Even though the FDA issued guidance in 2005 regarding evaluation of all new drugs for risk of inducing prolonged corrected QT interval (QTc) and torsades de pointes (TdP), the drugs hydroxychloroquine and chloroquine were already in use.
The Arizona Center for Education and Research on Therapeutics, a not-for-profit organization that reviews drug safety data, publishes information for prescribers and the public regarding risk of drugs that will prolong the QTc interval.
“Both HCQ and CQ are listed as having a known risk of TdP,” Desmarais and colleagues wrote in Arthritis & Rheumatology. “In 2017, the FDA also issued warnings on the potential cardiovascular toxicities of HCQ.”
There is a “clear need” for better understanding of the cardiovascular risk and safety profile of HCQ and CQ in managing rheumatic and cutaneous diseases, the authors said.
To examine current knowledge regarding antimalarial cardiac toxicity, analyze QTc prolongation and TdP risks, and determine future research needs, Desmarais and colleagues formed a working group of experts in rheumatology, cardiology and dermatology. Members performed a nonsystematic literature review and collectively expressed their consensus-based opinions.
The literature search, conducted throughout September 2020, resulted in the identification and review of 980 abstracts. The authors then participated in two virtual conferences to discuss the strengths and weaknesses of the collected data.
According to the authors, the current data “clearly indicate” that hydroxychloroquine and chloroquine are “invaluable medications in the management of rheumatic and dermatologic diseases.” However, both are associated with QTc prolongation by directly impacting cardiac repolarization, and those who prescribe these drugs should be aware of this effect, particularly in patients who receive additional medications that prolong the QTc interval.
Long-term antimalarial use may lead to a cardiomyopathy associated with arrhythmias and heart failure, the authors said. A risk-benefit assessment should be considered prior to the start of any drug, with both initial and ongoing assessments key to any prescription of hydroxychloroquine and chloroquine. Although cardiac toxicity related to antimalarial treatment of rheumatic diseases is rarely reported, it can be fatal, the authors added.
“There is the rare risk of TdP with the use of hydroxychloroquine/chloroquine,” Desmarais said. “Current data do not support specific recommendations to avoid these adverse effects, though options include baseline ECG in those with multiple risks and follow up ECG in cases of prolonged QTc or combination with other QTc-prolonging therapies.”
She noted that, “Hydroxychloroquine/chloroquine are important medications used in the treatment of autoimmune diseases, and risk of cardiac toxicity is felt to be low in comparison with the benefits of these medications. [However,] cardiomyopathy and conduction abnormalities have been reported with long term use of hydroxychloroquine/chloroquine, and providers should be vigilant to screen for cardiac symptoms in their patients.”
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Desmarais J, et al. Arthritis Rheumatol. 2021;doi:10.1002/art.41934.
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