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

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.