Since the World Health Organization declared COVID-19 as a Public Health Concern for Global Interests on January 30, more than one million tested positive for illness in the United States, and more than 62,000 have died. In the absence of FDA-approved treatments to date, the anti-malaria drug, hydroxychloroquine, has emerged as a potential therapy for pneumonia associated with COVID-19, with or without the antibiotic azithromycin.
In a short report published today at JAMA Cardiology, a team of pharmacists and doctors at Beth Israel Deaconess Medical Center (BIDMC), part of Beth Israel Lahey Health, found evidence that showed patients who received hydroxychloroquine for COVID-19 were at an increased risk of electrical changes in the heart and cardiac arrhythmias. The combination of hydroxychloroquine with azithromycin is associated with greater changes compared to hydroxychloroquine alone.
While hydroxychloroquine and azithromycin are generally well-tolerated drugs, increased use in the context of COVID-19 is likely to increase the frequency of adverse drug events (ADE). This is particularly concerning given that patients with underlying cardiac comorbidities appear to be disproportionately affected by COVID-19 and that the virus itself can damage the heart. “
Nicholas J. Mercuro, PharmD, first co-author, pharmaceutical specialist in infectious diseases at BIDMC
Hydroxychloroquine and azithromycin can respectively cause electrical disturbances in the heart known as QTc extension, shown by a longer distance between certain peaks on the electrocardiogram. The extension of QTc indicates that the heart muscle takes milliseconds longer than usual to refill between beats. Delay can cause cardiac arrhythmia, which in turn increases the chance of a heart attack, stroke, or death.
In this observational, retrospective, single center study, Mercuro and colleagues evaluated 90 adults with COVID-19 who were hospitalized at BIDMC between March 1 and April 7, 2020, and received at least one day of hydroxychloroquine. More than half of these patients also have high blood pressure, and more than 30 percent have diabetes.
Seven patients (19 percent) who received hydroxychloroquine alone developed QTc lasting 500 milliseconds or more, and three patients experienced changes in QTc of 60 milliseconds or more. Of the 53 patients who also received azithromycin, 21 percent had QTc that lasted 500 milliseconds or more, and 13 percent experienced a change in QTc of 60 milliseconds or more.
In our study, patients who were hospitalized and received hydroxychloroquine for COVID-19 often experienced extended QTc and adverse drug events. One participant who used a combination of drugs experienced a potentially lethal tachycardia called torsades de pointes, which to our knowledge has not been reported elsewhere in the COVID-19 literature reviewed by peers. “
Christina F. Yen, MD, first co-author, BIDMC Medical Department
In 2003, preliminary data showed that hydroxychloroquine might be effective against SARS-CoV-1, a fatal but difficult-to-transmit respiratory virus associated with coronavirus that causes COVID-19. Recently, a small study of patients with COVID-19 appears to benefit from anti-malaria drugs. However, subsequent studies failed to confirm both of these findings. Regarding their data, Gold and his colleagues urge caution and careful consideration before giving hydroxychloroquine as a treatment for COVID-19.
“When considering the use of hydroxychloroquine, specifically combined with azithromycin, doctors must carefully weigh the risks and benefits, and monitor QTc – especially considering the patient’s co-morbidity and concurrent drug use,” said senior author Howard S. Gold, MD, a specialist infectious disease at BIDMC and assistant professor of medicine at Harvard Medical School. “Based on our current knowledge, hydroxychloroquine for the treatment of COVID-19 may have to be limited to clinical trials.”
Mercuro, N.J., et al. (2020) The risk of prolongation of the QT interval associated with the use of hydroxychloroquine with or without concurrent azithromycin among inpatients who tested positive for Coronavirus 2019 (COVID-19). JAMA Cardiology. doi.org/10.1001/jamacardio.2020.1834.