Hydroxychloroquine/Azithromycin Therapy and QT Prolongation in Hospitalized Patients With COVID-19

Abstract

Objectives: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM).

Background: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population.

Methods: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality.

Results: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m² (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed.

Conclusions: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.

Keywords: COVID-19; QT prolongation; azithromycin; hydroxychloroquine; torsades de pointes.

Graphical abstract

Figure 1

Institutional Policy for QT Interval Monitoring Institutional policy for QT interval monitoring during inpatient administration of hydroxychloroquine and azithromycin (HCQ/AZM) in patients with COVID-19. ECG = electrocardiography; K = potassium; Mg = magnesium; QTc = corrected QT interval; TMS = telemetry monitoring system.

Figure 2

Screening, Inclusion, Exclusion, and QTc Monitoring Screening, inclusion, exclusion, and QTc monitoring for patients enrolled to assess the effects of HCQ/AZM on QTc prolongation. Abbreviations as in Figure 1.

Figure 3

QTc Measurements and Intervals (A) QTc measurements at baseline and days 1 through 5 of HCQ/AZM therapy in the study population of 415 patients. The data points representing QTc intervals ≥500 ms are highlighted red. (B) Change in QTc interval for days 1 through 5 of HCQ/AZM therapy compared with the baseline measurements in the subgroup of 137 patients with complete data from baseline, and days 1, 2 and/or 3, and 4 and/or 5. Patients who survived to hospital discharge or the termination of the study are depicted by blue squares, and patients who died in the hospital are depicted by red squares. The mean changes in QTc from baseline are depicted by the red and the blue lines, respectively. Compared with baseline, the mean QTc intervals increased on all days: p = 0.005 for days 1 and 2, and p < 0.001 for days 3 to 5. Abbreviations as in Figure 1.

Central Illustration

Prolongation of the QTc Interval in Hospitalized Patients With COVID-19 Examples of lead II ECG recordings from a patient admitted with severe COVID-19 infection at baseline (top left) and after 5 days of treatment with HCQ/AZM (bottom left) demonstrating significant prolongation of the QTc interval. Changes in the QTc interval after administration of HCQ/AZM compared to baseline values are shown (right panel). Patients that did not survive hospitalization are designated by solid red markers. COVID-19 = coronavirus disease-2019; ECG = electrocardiography; HCQ/AZM = hydroxychloroquine and azithromycin; QTc = corrected QT interval.