Pharmacotherapy Management for COVID-19 and Cardiac Safety: A Data Mining Approach for Pharmacovigilance Evidence from the FDA Adverse Event Reporting System (FAERS).

BACKGROUND

Several pharmacological agents, such as chloroquine/hydroxychloroquine, have been promoted for COVID-19 treatment or pre-exposure prophylaxis. However, no comprehensive evaluation of the safety of these possible agents is available, and is urgently needed.

OBJECTIVE

The purpose of this study was to investigate the risks of cardiac adverse events associated with the possible pharmacotherapies for COVID-19, including certain antimalarial, antiviral, and antibiotic drugs.

PATIENTS AND METHODS

We conduced retrospective pharmacovigilance analyses of the US Food and Drug Administration Adverse Event Reporting System database. The reporting odds ratio (ROR), a data mining algorithm commonly used in pharmacovigilance assessment, was generated to quantify the detection signal of adverse events.

RESULTS

Among individuals without coronavirus infection from 2015 Q1 to 2020 Q1, increased risks for cardiac disorders were found for antiviral agents such as chloroquine/hydroxychloroquine (ROR: 1.68; 95% confidence interval [CI] 1.66-1.70), lopinavir/ritonavir (ROR: 1.52; 95% CI 1.39-1.66), and antibiotics such as azithromycin (ROR: 1.37; 95% CI 1.30-1.44) and ceftriaxone (ROR: 1.92; 95% CI 1.80-2.05). Increased serious cardiac adverse events, including myocardial infarction, arrhythmia, and cardiac arrest, were also reported for these drugs. Further analyses of individuals with coronavirus infections revealed that 40% of individuals receiving chloroquine/hydroxychloroquine reported serious cardiac adverse events. Two cases resulted in QT prolongations and one case resulted in cardiac arrest. Chloroquine/hydroxychloroquine and azithromycin contributed to all the QT prolongation and cardiac arrest cases.

CONCLUSIONS

The current pharmacotherapies for COVID-19 are associated with increased risks of cardiac adverse events. Variations in the cardiac safety profiles of these pharmacotherapies were also observed. Clinicians should closely monitor patients with COVID-19, especially those at high risk, using chloroquine/hydroxychloroquine and azithromycin.