The effect of hydroxychloroquine and azithromycin on the QTc interval in patients with Covid-19

ABSTRACT

Background and Aim: The exact treatment method of Covid-19 has not been found so far. However, some small-scale studies have shown the potential benefit of hydroxychloroquine/chloroquine (hydroxychloroquine treatment in our country) and azithromycin in Covid-19 treatment. It is known that these drugs (alone or combined use) may increase the risk of malignant arrhythmia such as torsades de pointes (polymorphic ventricular tachycardia) with prolonged QT interval. There is no data showing the effect of Favipiravir on cardiac arrhythmia. In this study, we aimed to investigate the effect of hydroxychloroquine and azithromycin on the QTc interval in patient with Covid-19. Methods: Patients who hospitalized in our center between March and May 2020 for Covid-19 and treated with recommendations of Republic of Turkey Ministry of Health SARS-CoV-2 guide included in our study. The data of 142 consecutive patients who received hydroxychloroquine and/or azithromycin treatment were retrospectively analyzed and the QTc interval in ECG was calculated with the Bazzet formula. Patients who were already using hydroxychloroquine (i.e. because of autoimmune disease etc), hypersensitivity to hydroxychloroquine and/or azithromycin and patients who use drugs other than hydroxychloroquine and/or azithromycin that can prolong the QT interval were excluded. Patients with baseline QTc 500 milliseconds (msec) or longer were also excluded from the study. According to the protocol, ECG was performed all patients before treatment, and ECG controls were performed on the 1st, 3rd and 5th days of the treatment. Results: The mean age of the study population was 46.9±17.3. A total of 142 patients (50.7% male and 49.3% female), received hydroxychloroquine therapy, 36 patients (25%) received hydroxychloroquine monotherapy, while 106 patients (75%) received hydroxychloroquine and azithromycin combination therapy (Table 1). Majority of the patients were in sinus rhythm (%95,1) with mean baseline heart rate of 81.9±14.7 beats per minute. Mean baseline QTc values of 142 patients were 417.3±24 msec, ranging between 356-486 msec. There were no significant differences between the baseline, 1st, 3rd and 5th day's QTc values of two groups. (p>0.05). When each groups were evaluated for QTc prolongation during the therapy period, it was observed that the baseline QTc interval was significantly prolonged with treatment in both the hydroxychloroquine group and the hydroxychloroquine + azithromycin group (Table 2) (p<0.05). There were no patients required discontinuation of these medications, no malign arrhythmia and no arrhythmogenic deaths due to QTc prolongation (Table 3). Conclusions: Although treatment-related QTc prolongation is observed in our study population, no malignant arrhythmia was observed. Close monitoring of the treatment process by cardiologist and the predetermination of patients with long onset QTc distances are considered to be the most important factor in the safe management of the treatment.