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Some clinicians are using hydroxychloroquine (HCQ) and azithromycin (AZ) to treat patients with COVID-19 (NEJM JW Infect Dis Apr 24 2020; [e-pub]). Both are associated with risk for QT prolongation, although the incidence is unknown. Two simultaneously published reports provide data.
Mercuro and colleagues reported on 90 hospitalized COVID patients in Boston. Corrected QT (QTc) was measured before and after HCQ administration (dosage after day 1, 400 mg/day); 53 received concomitant AZ (dosage not given). The baseline median QTc was clearly longer than normal (HCQ-alone group, 472 milliseconds; HCQ+AZ group, 442 milliseconds). Seven patients (19%) receiving HCQ alone developed QTc ≥500 milliseconds, a generally agreed-upon measure to discontinue QT-prolonging drugs. For patients on combination treatment, 21% developed QTc ≥500 milliseconds. One patient with multiple cardiac and respiratory complications experienced torsades de pointes.
Bessière and colleagues reported on 40 French patients in an intensive care unit who were administered HCQ (400 mg/day for 10 days) either alone (45%) or combined with AZ (250 mg/day for 5 days; 55%). Baseline QTc was not prolonged in this cohort (median, 414 milliseconds). QTc ≥500 milliseconds was observed in 5% of those receiving HCQ alone and 33% of those receiving both medications. No arrhythmias were observed.
Mercuro NJ et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020 May 1; [e-pub]. (https://doi.org/10.1001/jamacardio.2020.1834)
Bessière F et al. Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit. JAMA Cardiol 2020 May 1; [e-pub]. (https://doi.org/10.1001/jamacardio.2020.1787)
Bonow RO et al. Hydroxychloroquine, coronavirus disease 2019, and QT prolongation. JAMA Cardiol 2020 May 1; [e-pub]. (https://doi.org/10.1001/jamacardio.2020.1782)
Comment
COVID-19 patients admitted to the hospital are quite ill and thus very different from most patients who received HCQ before the pandemic. Cardiac involvement is common, as is the use of concomitant drugs, many of which can also prolong QT. Indeed, the baseline QTc in the Boston study is much longer than medians in healthy populations. It is increasingly clear that the medications pose risk in these very sick patients. However, the risk-benefit ratio for HCQ, with or without AZ, is unknown — because efficacy is still unknown. These early studies should heighten our awareness, but they are replete with the problems of retrospective studies: The final word is still out.