Drug interaction as a predictor of direct oral anticoagulant drug levels in atrial fibrillation patients

Bruria Hirsh Raccah, Amihai Rottenstreich, Netanel Zacks, Mordechai Muszkat, Ilan Matok, Amichai Perlman, Yosef Kalish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Data are limited on the effects of drug interactions on direct-acting oral anticoagulant (DOAC) levels. We evaluated the effects of the use of interacting drugs on DOAC levels in patients with atrial fibrillation (AF). We reviewed data of AF patients tested for DOAC levels in 2013–2017. The primary outcomes were drug levels exceeding the expected steady-state range, and in the highest quartile. A multivariate analysis was performed to evaluate the correlation of treatment by the use of interacting drugs, CYP3A4 and P-glycoprotein (P-gp) inhibitors, with the primary outcomes. Overall, 147 patients underwent DOAC level measurement [dabigatran (n = 31), rivaroxaban (n = 29), apixaban (n = 87)]. Thirty-three (22.4%) had drug levels exceeding the expected range. Seventy-nine (53.7%) patients were treated with at least one interacting drug. In multivariate analysis, the concomitant use of interacting drugs was an independent predictor for drug levels exceeding the expected range (OR 3.3, 95% CI 1.20–9.05). The defined daily dose of the interacting drug correlated positively with DOAC levels (r = 0.29, P = 0.001). Co-treatment with interacting drugs was associated with extremely high levels of dabigatran, (OR 16.6, 95% CI 1.29–215.18) but not of the other DOAC examined. Concomitant use of interacting drugs is associated with high DOAC levels in patients with AF. Further investigation is warranted to establish the differences between specific DOAC, evaluate the effect on patient outcomes, and characterize the role of DOAC monitoring in this setting.

Original languageAmerican English
Pages (from-to)521-527
Number of pages7
JournalJournal of Thrombosis and Thrombolysis
Issue number4
StatePublished - 1 Nov 2018

Bibliographical note

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.


  • CYP3A4 inhibitors
  • Direct-acting oral anticoagulants
  • Drug interaction
  • Drug levels
  • P-gp inhibitors


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