Treating COVID-19 patients with hydroxychloroquine, alone or in combination with azithromycin, is associated with an increased risk of QTc prolongation, according to two new studies published in JAMA Cardiology.
The potential use of hydroxychloroquine to treat COVID-19 patients has been one of the biggest stories of this ongoing pandemic. The National Institutes of Health (NIH) has said “there are insufficient clinical data to recommend either for or against” such treatment, and it recommended against treating COVID-19 with both hydroxychloroquine and azithromycin.
In addition, the American Heart Association, American College of Cardiology and Heart Rhythm Society have urged physicians to use caution when using hydroxychloroquine and azithromycin to treat COVID-19 patients with pre-existing cardiovascular disease. And a recent study involving U.S. veterans found that treating the virus with hydroxychloroquine—with or without the addition of azithromycin—leads to an increase in overall mortality.
However, early anecdotal evidence has suggested these medications may truly help COVID-19 patients, and researchers continue to explore the topic.
In a new study out of Boston, for instance, the authors explored how hydroxychloroquine, alone or in combination with azithromycin, impacted QTc prolongation in 90 patients hospitalized with COVID-19. All patients were treated with at least one day’s worth of hydroxychloroquine, and another 53 patients received azithromycin as well. The cohort’s overall median baseline QTc was 455 milliseconds—it was 473 milliseconds for patients who received hydroxychloroquine alone and 442 seconds for those who received both medications.
Overall, the change in QT interval was greater for patients who received hydroxychloroquine and azithromycin. Twenty percent of the patients who were given hydroxychloroquine alone or in combination with azithromycin had a QTc prolongation of 500 milliseconds or more. Ten patients had hydroxychloroquine treatment stopped early due to “potential adverse drug events, including intractable nausea, hypoglycemia and one case of torsades de pointes.”
“Patients who were hospitalized and receiving hydroxychloroquine for COVID-19 frequently experienced QTc prolongation and adverse drug events, including a case of torsades de pointes with administration of hydroxychloroquine and azithromycin, which to our knowledge has yet to be reported elsewhere in the literature,” wrote lead author Nicholas J. Mercuro, PharmD, Beth Israel Deaconess Medical Center, and colleagues. “There is a critical need for rigorous, large-scale studies and risk-benefit assessment prior to initiating COVID-19 therapeutics, with careful attention to medication interactions, cardiac manifestations, routine electrocardiograms and electrolyte monitoring.”
In a separate study, researchers in France explored data from 40 COVID-19 patients treated in an intensive care unit (ICU) with hydroxychloroquine alone or in combination with azithromycin. In 93% of patients, an increase in QTc was detected. Prolonged QTc was present in 14 patients—10 had a QTc of more tan 60 milliseconds. No ventricular arrhythmias (or torsades de pointes) were recorded, but ECG abnormalities and acute renal failure led to treatment to end earlier than planned in 17 patients.
“This study raises safety concerns about the use of hydroxychloroquine with or without azithromycin for patients with COVID-19, particularly when both drugs are administered together,” wrote lead author Francis Bessière, MD, PhD, University of Lyon in France, and colleagues.
An accompanying article in JAMA Cardiology examined these findings in detail.
“The data showing increases in QTc in more than 90% of patients treated with these agents by Bessière et al. and in most patients reported by Mercuro et al., coupled with similar findings with chloroquine diphosphate in a Brazilian trial, underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19,” wrote lead author and JAMA Cardiology editor Robert O. Bonow, MD, MS, Northwestern University Feinberg School of Medicine. “Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed.”
Michael has more than 16 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.