Hospitalization for Hemorrhage Among Warfarin Recipients Prescribed Amiodarone

Amiodarone inhibits the hepatic metabolism of warfarin, potentiating its anticoagulant effect. However, the clinical consequences of this are not well established. Our objective in this study was to characterize the risk of hospitalization for a hemorrhage associated with the initiation of amiodarone within a cohort of continuous warfarin users in Ontario. We conducted a population-based retrospective cohort study among Ontario residents aged ≥66 years receiving warfarin. Among patients with at least 6 months of continuous warfarin therapy, we identified those who were newly prescribed amiodarone and an equal number who were not, matching on age, gender, year of cohort entry, and a high-dimensional propensity score. The primary outcome was hospitalization for hemorrhage within 30 days of amiodarone initiation. Between July 1, 1994, and March 31, 2009, we identified 60,497 patients with at least 6 months of continuous warfarin therapy, of whom 11,665 (19%) commenced amiodarone. For 7,124 (61%) of these, we identified a matched control subject who did not receive amiodarone. Overall, 56 (0.8%) amiodarone recipients and 23 (0.3%) control patients were hospitalized for hemorrhage within 30 days of initiating amiodarone (adjusted hazard ratio 2.45; 95% confidence interval, 1.49-4.02). Seven of 56 (12.5%) patients hospitalized for a hemorrhage after starting amiodarone died in hospital. In conclusion, initiation of amiodarone among older patients receiving warfarin is associated with a more than twofold increase in the risk of hospitalization for hemorrhage, with a relatively high fatality rate. Physicians should closely monitor patients who initiate amiodarone while receiving warfarin.