Abstract 1576: Pulmonary Toxicity Associated With Amiodarone: Population-Level Incidence and Risk Factors
Reports of the incidence of amiodarone associated pulmonary toxicity (AAPT) range from 1–10%, with most reports from clinical trials and small observational studies. Our study reports the first population-based incidence and potential predictors of AAPT in a real-world setting. We conducted a retrospective cohort study using linked administrative databases containing hospital discharge abstracts, prescription claims and vital status from Quebec, Canada between 1999 –2007. All patients 65+ years who were discharged alive with primary or secondary diagnoses of atrial fibrillation (AF) were included. Patients who had a diagnosis of pulmonary fibrosis within the prior year were excluded. Patients were identified as being “users” or “non-users” of amiodarone based on prescriptions dispensed within 7 days post-AF discharge. Pulmonary toxicity (PT) was defined through ICD-9/10 codes for pulmonary fibrosis, alveolar/interstitial lung disease, and adult respiratory distress syndrome. Potential risk factors of PT were explored using multivariable Cox regression. There were 6,492 users and 51,134 non-users of amiodarone in the cohort. PT occurred in 195/6,492 (3%) amiodarone users and 496/51,134 (1%) non-users. The crude incidence of AAPT in male and female users was 19.92 and 13.03/1000 person-years, respectively. Crude incidence rose to 49.24 and 29.09/1000 person-years, respectively, by sex, with amiodarone doses of 400mg daily. PT was significantly associated with amiodarone exposure in a dose-related manner in multivariable models (≤200mg daily: HR 1.56 [1.31– 1.85]; >200mg daily: 1.91 [1.27– 2.87] vs. no amiodarone). Other predictors of PT included increasing age (1.02 [1.01–1.03] per year), male sex (1.58 [1.34 –1.86]), COPD (2.15 [1.84 –2.51]), heart failure (1.20 [1.02–1.41]), hypothyroidism (1.32 [1.08 –1.60]), renal disease (1.25 [1.02–1.53]), and liver disease (1.48 [1.02–2.16]). Population-based incidence of AAPT is in the lower range of what has been previously reported. However, amiodarone users with AF have an approximately 2-fold higher risk of PT than non-users. A greater risk of PT was associated with higher dose, male sex, and comorbidities primarily linked to amiodarone metabolism.