NEW YORK (Reuters Health)—Potentially dangerous prolongation of the QT interval is common among patients hospitalized with COVID-19 who receive hydroxychloroquine (HCQ) with or without concomitant azithromycin, according to two new studies.
“This is a well-known problem with HCQ and azithromycin, which became amplified in this higher risk population,” Christina F. Yen, MD, from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, told Reuters Health by email.
In the first study, Dr. Yen and colleagues sought to characterize the risk and degree of QT prolongation in 90 patients with COVID-19 in association with their use of HCQ with or without concomitant azithromycin.
One-third of these patients were critically ill at the time of testing, and 26% were mechanically ventilated. All patients received HCQ, and 59% also received azithromycin. Most patients had at least one cardiovascular mortality and were taking two or more QTc-prolonging medications.
Median corrected QT interval (QTc) was 455 ms at baseline. With treatment the QTc increased by 60 ms or more in 10 patients (11%) and 18 patients (20%) had posttreatment QTc of 500 ms or more.
The number of patients who developed prolonged QTc of 500 ms or more was greater with concomitant azithromycin (11/53, 21%) than with HCQ monotherapy (7/37, 19%), as was the percentage of patients whose QTc increased by 60 ms or more (13% versus 3%, respectively), according to the online report in JAMA Cardiology.1
Concomitant loop diuretic administration and a baseline QTc of 450 ms or more were independently associated with an increased likelihood of prolonged QTc.
Adverse events possibly related to HCQ treatment included intractable nausea, development of new premature ventricular contractions and right bundle branch block, and hypoglycemia.
One patient whose hydroxychloroquine and azithromycin were discontinued because of QTc prolongation (499 ms) developed torsades de pointes three days later and subsequently developed other ventricular arrhythmias that required lidocaine treatment.
“This highlights hydroxychloroquine’s long half-life, allowing QTc prolonging effects to linger even after discontinuation,” Dr. Yen says.
“This study underscores that use of HCQ and azithromycin in hospitalized COVID-19 patients must be done cautiously and ideally in the setting of a clinical trial, as recommended by multiple international guidelines,” she says. “We hope that those seeking to use HCQ, with or without azithromycin, consider our study and other peer-reviewed data regarding the safety and efficacy of these drugs for the treatment of COVID-19. It is not clear that our current understanding of the risk/benefit of HCQ favors its use for COVID-19.”