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Safety and Interactions of Direct Oral Anticoagulants with Antiarrhythmic Drugs

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Abstract

Direct oral anticoagulants (DOACs) are novel direct-acting medications that are selective for either thrombin or activated factor X. Due to their obvious benefits for patients (fewer interactions, broader therapeutic window, etc.), they are increasingly used as an alternative to warfarin, phenprocoumon, or acenocoumarol. One of the major indications for use of DOACs is stroke prevention in patients with atrial fibrillation (AF). However, interactions still exist, especially in combination with antiarrhythmic drugs (AADs), which are frequently given to AF patients for rhythm or rate control. These interactions are due to the cytochrome P450 system and the P-glycoprotein (permeability glycoprotein or multidrug resistance protein) transport system. For some combinations, dose reduction of the DOAC is recommended and in some cases contraindications exist. In addition, impairment in renal and hepatic function plays an important role in this context. However, compared with pure interactions where data are quite convincing, the latter topic has been studied only rudimentarily. This review summarizes the literature on the safety and interactions of AADs when used with DOACs [dabigatran (a direct inhibitor of factor IIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa)] and the impact of renal and hepatic impairment.

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Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Kocaeli University, 41380, Kocaeli, Turkey

    Ipek Celikyurt

  2. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, 4031, Basel, Switzerland

    Christoph R. Meier

  3. Hospital Pharmacy, University Hospital Basel, 4031, Basel, Switzerland

    Christoph R. Meier

  4. Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA

    Christoph R. Meier

  5. Department of Cardiology, University Hospital Basel, Petersgraben 4, CH 4031, Basel, Switzerland

    Michael Kühne & Beat Schaer

Authors
  1. Ipek Celikyurt
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  2. Christoph R. Meier
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  4. Beat Schaer
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Correspondence to Beat Schaer.

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No sources of funding were used to assist in the preparation of this study.

Conflicts of Interest

Ipek Celikyurt, Christoph R. Meier, and Beat Schaer have no conflicts of interest that are relevant to the content of this study. Michael Kühne has received honoraria from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Pfizer-BMS for advisory boards and lectures.

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Celikyurt, I., Meier, C.R., Kühne, M. et al. Safety and Interactions of Direct Oral Anticoagulants with Antiarrhythmic Drugs. Drug Saf 40, 1091–1098 (2017). https://doi.org/10.1007/s40264-017-0567-5

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