Most patients with COVID-19 who are treated with hydroxychloroquine and azithromycin experience QTc prolongation despite undergoing pre-treatment ECG screening, US cardiologists have warned.
In a letter published in Nature Medicine, Dr Leon Charney and colleagues from the Division of Cardiology, New York University School of Medicine, describe their observation in 84 patients with COVID-19 who were treated at a centre in New York.
The patients were, on average, 63 years of age and 74% were male. They were treated with hydroxychloroquine at a dose of 400 mg twice daily on the first day, followed by 200 mg twice daily. Azithromycin was given at a dose of 500 mg per day.
ECG follow-up after 4-5 days showed that all patients had some degree of prolongation of the QTc, with the overall level increasing from a baseline average of 435 ± 24 ms (mean ± s.d.) to a maximal average value of 463 ± 32 ms (P < 0.001).
Nine of the 84 patients (11%) had QTc that was severely prolonged to >500 ms, putting them at high risk of malignant arrhythmia and sudden cardiac death. Five of the nine patients with severe QTc prolongation had a normal QTc at baseline.
In this high-risk group, the QTc increased from a baseline average of 447 ± 30 ms to 527 ± 17 ms (P < 0.01).
Four patients in the cohort died from multiple organ failure, without evidence of arrhythmia and without severe QTc prolongation.
The authors said it was notable that so many patients with COVID-19 disease had QT prolongation despite a normal QTc at baseline. This suggested hydroxychloroquine cardiotoxicity may be influenced by attributes such as the presence of co-morbidities and the severity of the disease, they said.
“We therefore suggest that the QTc should be followed repeatedly in patients with COVID-19 who are treated with hydroxychloroquine/azithromycin, particularly in those with co-morbidities and in those who are treated with other QT-prolonging medications.
In its most recent advice the Australian Health Protection Principal Committee (AHPPC) said there it was not recommended to use hydroxychloroquine as prophylaxis, except in clinical trials.
“Due to safety concerns, and the unknown effects of prescribing these medications for off-label usage, such as for COVID-19 infection, there are no current recommendations to treat patients with mild to moderate COVID-19 illness,” it said in a statement released on 7 April
“Appropriate dosage of medications for use in COVID-19 are not yet determined, and there is concern that if used inappropriately, off-label use of medications may cause toxicity and lead to adverse patient outcomes.”
“For deteriorating or critically ill patients, supportive care is still currently recommended as best practice. Experimental use of medications is not recommended, and should only be prescribed as part of a clinical trial.”