QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin

Abstract

BACKGROUND There is no known effective therapy for patients with coronavirus disease 2019 . Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/ AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).OBJECTIVE The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.METHODS This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. RESULTSThe QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion.Extreme new QTc interval prolongation to .500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.CONCLUSION The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.

Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir

“…Unfortunately, on the clinical aspect, LPV/r failed to demonstrate clinical benefits in well-powered randomized controlled trials (RCTs), while HCQ and/or AZ also failed to demonstrate benefits in observational studies (12)(13)(14). Meanwhile, LPV/r, CQ/HCQ and AZ may even increase the incidence of adverse events (14)(15)(16). Although remdesivir is widely considered one of the most promising candidates, latest RCTs only revealed marginal shortening of disease duration in patients treated (17).…”

Mitigating Arrhythmia Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia Risk Management Plan

“…One case of torsades de pointes (TdP) which happened three days after discontinuation of treatment may indicate delayed risk possibly due to long half-life of HCQ (11). A larger retrospective cohort study of 251 subjects showed prolongation of QTc≥500 ms in 15.9 % of subjects with 1 case of TdP (12). The timing of peak ΔQTc of this study was at the end of the 5-day treatment scheme.…”

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

“…Despite the fact that HCQ/CQ were commonly used for rheumatoid arthritis and systemic lupus erythematosus in the general population, there has been major concern with widespread use of these medications for COVID-19 due to possible QTc prolongation and induction of life-threatening arrhythmias. There is general consensus that QTc prolongation after HCQ/CQ use may occur in a dose-dependent way [11,[32][33][34][35]. Previous studies demonstrated that HCQ/CQ block the hERG potassium channels, extending ventricular repolarization and action potentials, and hence, may trigger ventricular tachyarrhythmias [36,37].…”