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The effect of amiodarone on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population.

Authors
  • Holm, J1
  • Lindh, J D1
  • Andersson, M L1
  • Mannheimer, B2
  • 1 Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. , (Sweden)
  • 2 Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. , (Sweden)
Type
Published Article
Journal
Journal of thrombosis and haemostasis : JTH
Publication Date
Mar 01, 2017
Volume
15
Issue
3
Pages
446–453
Identifiers
DOI: 10.1111/jth.13614
PMID: 28058824
Source
Medline
Keywords
License
Unknown

Abstract

Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as co-medication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. Objectives An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nationwide registries. Patients/Methods In a retrospective cohort study including 754 patients, warfarin doses were compared between two 4-week periods, before and 18-21 weeks after initiating co-treatment with amiodarone. In addition, warfarin doses and international normalized ratio (INR) values were calculated week-by-week after the initiation of amiodarone. Results The initiation of amiodarone increased the mean INR from 2.6 to 3.1. The proportion of patients with a supratherapeutic INR over 3.0 and 4.0 increased from 12% to 37% and 0.9% to 5.5%, respectively. The subsequent mean decrease in warfarin dose was 24.6% (95% confidence interval [CI], 23.5, 25.6). The frequency of INR monitoring within 1 and 2 weeks after initiation of amiodarone was 67% and 90%. Conclusions Although warfarin doses in most patients were within the therapeutic range, more than one in three patients initiating co-treatment with amiodarone were exposed to a supratherapeutic anticoagulative effect within 3 weeks. In order to further avoid severe unnecessary bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring, anticipating an average dose reduction of 25%.

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