Antimalarial agents for COVID-19 may be cardiotoxic

Use of chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19 appears to promote QT prolongation and lead to an increased incidence of events such as torsade de pointes (TdP), ventricular tachycardia (VT), and cardiac arrest, according to a study.

The study was a meta-analysis of 19 studies that described cardiac toxicities in a total of 5,652 patients COVID-19 patients treated with CQ or HCQ, with or without azithromycin.

One study reported the incidence of any arrhythmia (unspecified) and cardiac arrest in 19.3 percent and 15 percent of 1,006 patients who received HCQ alone or in combination with azithromycin. In six studies, non-sustained VT occurred in 0–5 percent of patients treated with CQ or HCQ. On the other hand, sustained VT developed in 0–2.7 percent of patients in nine studies. Only two studies found a signal for new-onset atrial fibrillation, detected in 8.5–12.8 percent of patients.

There were four studies reporting on conduction abnormalities, which occurred in 1–3.4 percent of their patients. Meanwhile, two studies observed acute cardiac injury, defined as elevated troponin levels in 27.8 percent of patients and as elevated cardiac specific creatine phosphokinase (CKMB) in 31.8 percent of patients. In the last study, the CKMB elevation was greater with high vs lower CQ dose (50 percent vs 31.6 percent).

Finally, two studies documented acute MI in up to 17 percent of the patients. Acute myocarditis was observed in three patients from two studies.

Pooled data showed that TdP arrhythmia or VT or cardiac arrest had an incidence rate of 3 per 1,000 patients (I², 96 percent; 18 studies; n=3,725). CQ or HCQ was discontinued due to these adverse events in 5 percent of patients (I², 98 percent; 13 studies; n=4,334 patients). The incidence of change in QTc from baseline of ≥60 or ≥500 ms was 9 percent (I², 97 percent).

There was between-studies heterogeneity, which was attributed to mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations.

The present data highlight the importance of adequate monitoring of COVID-19 patients who are treated with antimalarials for other indications.