Background: Amiodarone-induced pulmonary toxicity (APT) is the most serious side-effect of amiodarone, and its detection and prevention are extremely important. This study was designed to evaluate the incidence and clinical risk factors of APT, and the utility of a pulmonary function test or serum KL-6 assay to predict pulmonary toxicity in Japanese patients receiving low-dose amiodarone.
Methods and results: Five hundred consecutive patients receiving amiodarone were retrospectively evaluated. Mean follow-up period was 48 months and mean maintenance dose was 141 mg daily. Cumulative incidence of APT was 4.2%, 7.8%, and 10.6% at 1, 3, and 5 years, respectively. On multivariate analysis, age at the start (hazard ratio (HR) =1.48, 95% confidence interval (CI) 1.13 to 1.93) was a significant pretreatment risk factor. Age (HR =1.64, 95% CI 1.29 to 2.09), maintenance dose (HR =1.90, 95% CI 1.45 to 2.49) and plasma monodesethylamiodarone concentration (HR =1.30, 95%CI 1.08 to 1.58) were risk factors. Sensitivity and specificity in screening with measurement of percent predicted diffusion capacity of carbon monoxide, > or =15% individual decrease, were 68% and 69%, and for > or =20% individual decrease, were 59% and 74%, whereas those in screening with serum KL-6 assay, > or =500 U/ml, were 25% and 91%, respectively.
Conclusions: Even at low dose, amiodarone shows substantial pulmonary toxicity. Higher age and higher maintenance dose are risk factors. Further decreasing the maintenance dose of amiodarone should be considered in order to reduce the incidence of pulmonary toxicity, at least in Japanese patients.