Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen

Abstract

Background Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. Methods A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). Results A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3452 ± 26.4 vs Group 2436.3 ± 28.4 vs Group 1424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. Conclusions The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

Coronavirus disease 2019 (COVID-19) and QTc prolongation

“…Considering the sample size, the study is likely underpowered to determine this. Other observational studies also have failed to show this association but are limited by small sample size [15][16][17][18][19].…”

“…However, the recent RECOVERY trial (Randomized evaluation of COVID-19 therapy) failed to show any benefit of hydroxychloroquine in COVID-19 patients and on the contrary showed some signals towards harm [ 16 ]. Some recent observational studies have also pointed to the association of QTc prolongation in COVID-19 with the use of hydroxychloroquine and/or azithromycin [ 17 – 20 ]. Our study provides further evidence to the association of QTc prolongation with the use of hydroxychloroquine and azithromycin in this population.…”

Prevention and treatment of COVID-19: Focus on interferons, chloroquine/hydroxychloroquine, azithromycin, and vaccine

“…It was recorded in several countries on COVID-19 patients treated with HCQ/AZM combination with prolongations exceeding 500 ms in some studies [ 158 , 176 ]. The rate of HCQ/AZM treated patients presenting QT prolongation ranges from 0.77 % to 61 %, according to some studies [ 158 , 176 , 179 ]. The polymorphic ventricular tachycardia or fibrillation, acute kidney failure, and resuscitated cardiac arrest were also recorded in the patients under HCQ/AZM treatment [ 169 , 177 ].…”

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

“…Consequently, Hydroxychloroquine has been promoted as a potential treatment of COVID-19. However, 4–61% of COVID-19 patients treated with Hydroxychloroquine and Chloroquine developed cardiotoxicity, primarily QT prolongation and Torsades de Pointes ( Afsin et al , 2020 ; Bernardini et al , 2020 ; Borba et al , 2020 ; Chorin et al , 2020 ; Hooks et al , 2020 ; Jankelson et al , 2020 ; Lalabekyan et al , 2020 ; Mercuro et al , 2020 ; Saleh et al , 2020 ; Szekely et al , 2020 ).…”