Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin

Abstract

Background: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. Methods: We performed 12-lead ECGs and 12-lead 24-h Holter ECG monitoring in all patients aged b80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. Results: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p b .01) compared with those with QTc b 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. Conclusion: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.

Electrocardiograhic characteristics in patients with coronavirus infection: A single‐center observational study

“…Hydroxychloroquine (HCQ), lopinavir/ritonavir, and azithromycin have been confirmed to prolong the QTc interval in patients with COVID-19 (Sacher et al, 2020). Moreover, some inflammatory factors (TNF-α, IL-6) and electrolyte disturbance may potentially contribute to this process (Cipriani et al, 2020).…”

Azithromycin in COVID-19 Patients: Pharmacological Mechanism, Clinical Evidence and Prescribing Guidelines

“…However, these findings have been refuted by several recent studies evaluating the effects of this association on QT interval in COVID-19 patients. These studies indicate that the use of azithromycin with chloroquine/hydroxychloroquine could significantly prolong QT interval, especially in patients affected by severe COVID-19 and in the presence of comorbidities, suggesting using this association with caution [62][63][64][65][66]. According to the Liverpool Drug Interactions group, electrocardiogram monitoring is recommended in patients treated with chloroquine/hydroxychloroquine and other QT-prolonging drugs including azithromycin [67].…”

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients

“…LPN/RTN causes the dose-dependent block of both human ether-a-go-go-related gene (HERG) potassium channels and delayed rectifier potassium current (IKr) channels predisposing to QT prolongation and torsade de pointes (TdP) ( Anson et al, 2005 ; Russo et al, 2020b ). Increased corrected QTc interval (QTc) has been reported in hospitalized COVID-19 patients treated with HQ/AZT ( Bun et al, 2020 ; Chorin et al, 2020 ; Cipriani et al, 2020 ; Hor et al, 2020 ; Mercuro et al, 2020 ; Ramireddy et al, 2020 ) alone or in combination, due the inhibitory effects on IKr channels. The concomitant use of three or more QT prolonging drugs twice increases the risk of QT prolongation in hospitalized patients on cardiology ward ( Khan et al, 2017 ); however, no data on the effect of triple combination therapy with LPN/RTN, HQ and AZT on corrected QT (QTc) interval and arrhythmic risk have been still provided.…”