Does hydroxychloroquine with concomitant azithromycin increase the risk of QT interval prolongation compared to hydroxychloroquine alone in hospitalized patients with COVID-19 pneumonia?
In hospitalized patients with COVID-19, hydroxychloroquine use is associated with a high risk of QTc prolongation, which is significantly exacerbated by the addition of azithromycin.
IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients 53.3%) and diabetes mellitus (in 26 patients 28.9%) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 454-487 milliseconds vs hydroxychloroquine and azithromycin, 442 427-461 milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 10-40 milliseconds) compared with those receiving hydroxychloroquine alone (5.5 -15.5 to 34.25 milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 95% CI, 1.03-11.08) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 95% CI, 1.75-28.87). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.
Mercuro et al. (Fri,) studied this question.