Association between amiodarone and thyrotoxicosis in patients with atrial fibrillation and hypothyroidism

Evidence remains scarce on the risk of transition from hypothyroidism to thyrotoxicosis in patients treated with amiodarone.

This study aimed to assess the association between amiodarone and thyrotoxicosis in patients with atrial fibrillation (AF) and concomitant diagnosis of hypothyroidism.

We conducted a population-based retrospective cohort study using the Clalit Health Services database, the largest health care provider in Israel. Patients with a new diagnosis of AF between 2010 and 2023 were used to identify 2 separate cohorts defined based on their thyroid function status (hypothyroidism cohort vs normal thyroid cohort). Using Cox proportional hazard regression, exposure to amiodarone was examined as a time-dependent variable, allowing subjects to transfer from one exposure group to another during follow-up.

A total of 23,854 patients with AF were included in the hypothyroidism cohort, with thyrotoxicosis diagnosed during follow-up in 107 patients (66 of 8212 amiodarone users and 41 of 15,622 non-users), reflecting a crude incidence rate of 3.43 and 0.63 per 1000 person-years in amiodarone users and non-users, respectively. In this cohort, amiodarone was independently associated with increased risk of thyrotoxicosis with an adjusted hazard ratio of 5.18 (95% confidence interval [CI], 3.48-7.69). The magnitude of amiodarone effect was higher in patients with normal thyroid function, with an incidence rate of 19.78 and 1.14 per 1000 person-years in amiodarone users and non-users, respectively, and an adjusted-hazard ratio of 15.02 (95% confidence interval, 13.56-16.64).

Although the magnitude of the effect of amiodarone on the risk of thyrotoxicosis is lower in patients with hypothyroidism, the risk remains elevated and mandates caution.