Кардиотоксичность хлорохина и гидроксихлорохина при лечении инфекции COVID-19

Abstract

The cardiotoxicity of aminoquinolines presents as QT interval prolongation and life-threatening ventricular arrhythmia, torsade de pointes (TdP). A scientific re-view of studies and meta-analyzes on the rate and risk of cardiotoxicity of aminoquinolines (chloroquine and hydroxychloroquine) is presented. The mechanism of development of QT syndrome during the use of aminoquinolines is associated with inhibition of the hERG gene open potassium channels 1A and 1A/1B, which are involved in the repolarization process, as well as inhibition of potassium, calcium and If-channels of the heart, which leads to an impaired conduction and bradycardia. In 3 systematic review of data (1962–2018) of analysis of cardiotoxic side effects of chloroquine, hydroxychloroquine, mefloquine in the treat-ment of malaria and connective tissue diseases, isolated cases of death due to QT interval prolongation/TdP arrhythmia were revealed, however, data on the rate of detecting QT interval prolongation was not enough. In the face of the COVID-19 novel coronavirus pandemic emergency, aminoquinolines are being re-purposed by the Food and Drug Administration – FDA (repurposing) to treat severe acute respiratory syndrome in hospitalized patients. Chloroquine and hy-droxychloroquine were intended to be administered in short courses with QT monitoring. However, the first data of clinical trials have revealed an increased risk for hospital mortality in patients with COVID-19. In the first systematic review of studies in COVID-19 (14 clinical trials, n=1515), a clinically significant QT interval prolongation (QT≥500 ms or change of more than 60 ms) in 10% of patients receiving chloroquine/hydroxychloroquine, and isolated cases of fatal arrhythmia was revealed. Subsequent studies showed that the incidence of QT interval prolongation during the use of chloroquine/hydroxychloroquine ranges from 10 to 23%, with isolated cases of ventricular arrhythmia TdP, but there is a significant increase in mortality (relative risk – RR 1.3–1.50) and sudden cardiac arrest (RR 1.91), especially in combination with azithromycin (RR>2.0). The FDA and the World Health Organization have limited the use of drugs for COVID-19. Perspectives for further treatment of COVID-19 infection are associated with remdesivir and favipiravir.