Comparison of hydroxychloroquine plus moxifloxacin versus hydroxychloroquine alone on corrected QT interval prolongation in COVID-19 patients

ABSTRACT

Background: Hydroxychloroquine (HCQ) alone or with some antibiotic and antiviral agents is used off label in the treatment of Coronavirus Disease 2019 (COVID-19). It seems that the most important safety problem about these medications are their cardiac side effects. Although there are data on arrhythmogenic events associated with the use of HCQ alone, such as corrected QT (QTc) prolongation, Torsade de pointes (TdP) or bradycardia, there are insufficient data on its combination with moxifloxacin (MOX). Objective: The aim of our study is to analyze the effect of HCQ alone or in combination with the use of MOX on QTc interval, heart rate, and arrhythmic events in patients with a diagnosis of COVID-19. Methods: This is a single center cohort study of non-intensive care unit (ICU) patients hospitalized with clinical signs consistent with pneumonia and at least one positive COVID-19 nasopharyngeal polymerase chain reaction test result. QTc intervals and heart rates in patients whose treatment consisted of HCQ alone or its separate combination with MOX at baseline and post-treatment were calculated and compared. Results: 312 patients were included (median age of 42 [IQR 31.25-57.75] years, 54.16% male). Patients were divided into two groups based on their in-hospital treatment strategy as follows HCQ alone (n 166, 53.20%) or HCQ + MOX (n 146, 46.79%). As compared to baseline, QTc intervals were significantly increased in all patients after treatment (406.00 [388.00-422.00] ms vs 418.00 [401.00-435.00] ms, p<0.001). When the baseline QTc intervals were evaluated, there was no statistically significant difference between HCQ alone and HCQ + MOX groups (403.00 [384.50-419.00] ms vs. 409.50 [390.00-425.00] ms, p 0.086). After treatment period, QTc intervals were significantly higher in HCQ + MOX group compared to the group in which patients only used HCQ (413.00 [398.00-430.00] ms vs. 426.50 [405.00-441.00] ms, p<0.001). We found a significant decrease in heart rate in both groups after treatment period. From 79.00 (70.00-88.00) bpm to 70.00 (63.00-79.00) bpm in HCQ alone group (p<0.001) and from 80.00 (70.00-88.00) bpm to 70.50 (63.00-78.75) bpm in HCQ + MOX group (p<0.001). On the other hand, no statistically significant difference was observed between the groups in terms of heart rates either before or after the treatment. Conclusion: In this cohort study, patients who received HCQ for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with MOX was associated with greater changes in QTc. However, none of patients experienced malignant ventricular arrhythmia or death during treatment. Clinicians should carefully weigh risks and benefits with close monitoring of QTc if considering treatment with HCQ especially concomitant use with MOX. Further prospective studies are needed to determine the exact implications of these drugs on arrhythmias in patients with COVID-19.