Increased hospitalization for hemorrhages in patients taking amiodarone with warfarin: a population-based cohort study

Abstract

<p><strong>BACKGROUND</strong></p> <p>Amiodarone is believed to inhibit the hepatic metabolism of warfarin, potentiating its hypoprothrombinemic effect and increasing the risk of hemorrhage. The consequences of this drug interaction on important clinical outcomes are unknown.</p> <p><strong>METHODOLOGY</strong></p> <p>Using linked health administrative databases, we conducted a population-based retrospective cohort study among Ontario residents aged 66 years or older who had been treated with warfarin therapy for at least 6 months. Within this group, we identified subjects who initiated amiodarone while on warfarin. Each of these subjects was matched to a subject not treated with amiodarone on age, sex, year of cohort entry, and a high dimensional propensity score. The primary outcome was a hospitalization due to a hemorrhagic event within 30 days of follow-up. In a secondary analysis, we examined in-hospital mortality following hospitalization for major hemorrhage.</p> <p><strong>RESULTS</strong></p> <p>We identified 60,497 eligible patients between July 1, 1994 and March 31, 2009. Of these, 11,665 (19.3%) received a new prescription for amiodarone while receiving ongoing warfarin therapy and 7,124 (61.1%) of these were matched to a subject who was not exposed to amiodarone while receiving warfarin therapy. The median age at cohort entry of the matched cohort was 76 years, 51.6% in the cohort were male, 14.5% lived in a rural location, 2.8% had a bleed in the past year, and 21.6% had a diagnosis of congestive heart failure in the past year. Fifty-six amiodarone recipients experienced a hemorrhagic event (0.8%) as compared to 23 individuals (0.3%) in the non-exposed group at 30 day follow-up (adjusted hazard ratio (HR) = 2.45; 95% CI, 1.49 to 4.02). Seven patients in the amiodarone group died after hospitalization for a hemorrhage versus four in the non-exposed group (adjusted HR = 1.74; 95% CI, 0.25 to 12.24).</p> <p><strong>CONCLUSION</strong></p> <p>Initiation of amiodarone in patients on chronic warfarin therapy was associated with a two-fold increase in the risk of hospitalization due to a hemorrhagic event. Physicians should closely monitor the response to warfarin following initiation of amiodarone.</p>