Amiodarone-related thyroid dysfunction and associated outcomes in patients with heart failure—A nationwide cohort study

Abstract

Aim

Amiodarone increases the risk of thyroid dysfunction, but the prognostic significance of this complication in patients with heart failure (HF) is uncertain. This study investigates the association between amiodarone-related thyroid dysfunction and risk of HF hospitalization or death in a nationwide cohort.

Methods

Cases and controls were identified from a source population of all HF patients who initiated treatment with amiodarone from 1996 to 2021. Patients diagnosed with and/or treated for thyroid dysfunction within 3 years of starting amiodarone were classified as cases and comprised the study population together with controls matched 1:2 based on age, sex, calendar year, and HF duration. The primary outcome was a composite of HF hospitalization and death within 1 year from onset of thyroid dysfunction, analyzed using Kaplan–Meier curves and Cox regression models adjusted for comorbidities.

Results

Of 21,947 HF patients who initiated amiodarone, 2972 (14%) developed thyroid dysfunction. After matching, the study population consisted of 2953 cases and 5857 controls, mean age 70 years, and 65% men. At 1-year follow-up the primary outcome occurred in 1154 (39%) cases and 1826 (31%) matched controls, yielding an adjusted hazard ratio (HR) of 1.30 (95% CI 1.21–1.40). This increased risk was observed for both HF hospitalization (30% vs. 23%, HR 1.35 [1.24–1.47]) and all-cause death (19% vs. 15%, HR 1.21 [1.08–1.34]).

Conclusions

In this nested case–control study derived from a nationwide cohort of amiodarone-treated HF patients, new-onset thyroid dysfunction was associated with a 30% higher risk of a composite of HF hospitalization and death within 1 year.