Amiodarone for the Treatment of Arrhythmias in COVID-19 Patients Does Not Increase the Risk of Pulmonary Fibrosis: A Retrospective Cohort Study

Abstract

Amiodarone is a class III antiarrhythmic medication used to treat atrial and ventricular tachyarrhythmias. Pulmonary fibrosis from amiodarone use is a well-documented side effect. Pre-COVID-19 pandemic studies have shown that amiodarone-induced pulmonary fibrosis occurs in 1%-5% of patients and usually occurs between 12 to 60 months after initiation. The risk factors associated with amiodarone-induced pulmonary fibrosis include a high total cumulative dose (treatment longer than two months) and high maintenance dose (>400 mg/day). COVID-19 infection is also a known risk factor for developing pulmonary fibrosis and occurs in approximately 2%-6% of patients after a moderate illness. This study aims to assess the incidence of amiodarone in COVID-19 pulmonary fibrosis (ACPF). This is a retrospective cohort study with 420 patients with COVID-19 diagnoses between March 2020 and March 2022, comparing two populations, COVID-19 patients with exposure to amiodarone (N=210) and COVID-19 patients without amiodarone exposure (N=210). In our study, pulmonary fibrosis occurred in 12.9% of patients in the amiodarone exposure group compared to 10.5% of patients in the COVID-19 control group (p=0.543). In multivariate logistic analysis, which controlled for clinical covariates, amiodarone use in COVID-19 patients did not increase the odds of developing pulmonary fibrosis (odds ratio (OR): 1.02, 95% confidence interval (CI): 0.52-2.00). The clinical factors associated with the development of pulmonary fibrosis in both groups included a history of preexisting interstitial lung disease (ILD) (p=0.001), exposure to prior radiation therapy (p=0.021), and higher severity of COVID-19 illness (p<0.001). In conclusion, our study found no evidence that amiodarone use in COVID-19 patients increased the odds of developing pulmonary fibrosis at six-month follow-up. However, long-term amiodarone usage in the COVID-19 population should be based on the physician's discretion.

Keywords: amiodarone; antiarrhythmics; atrial fibrillation; covid-19; cytokines; dose-dependent toxicity; outcomes research; pulmonary fibrosis; renin-angiotensin-aldosterone system; safety profile.

Figure 1. Study design

COVID-19: coronavirus disease 2019, ACLS: advanced cardiovascular life support

Figure 2. Summary of risk of pulmonary fibrosis in COVID-19 patients exposed to amiodarone at six-month follow-up

OR plot comparing the incidence of pulmonary fibrosis between the amiodarone and COVID-19 exposure group and the COVID-19 without amiodarone exposure group Model A, unadjusted model; Model B, adjusted for age and sex; Model C, adjusted for age, sex, history of interstitial lung disease and chronic obstructive lung disease, prior smoking history, and severity of COVID-19 illness COVID-19, coronavirus 2019; OR: odds ratios