Cardiovascular Drugs and Therapy

, Volume 32, Issue 6, pp 591–600 | Cite as

Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants

  • Xue Feng
  • Usha Sambamoorthi
  • Kim Innes
  • Gregory Castelli
  • Traci LeMasters
  • Lianjie Xiong
  • Michael U. Williams
  • Xi TanEmail author



This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF).


We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events.


Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02–1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48–1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events.


The number and duration of potential DDIs and patients’ comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.


Drug-drug interactions Atrial fibrillation Bleeding Switching Non-vitamin K oral anticoagulants 



We used an adjudicated claims database of commercially insured individuals, which is made available through a license to IQVIA’s Real World Data: Adjudicated Claims - US (also known as PharMetrics Plus), 10% sample. All Rights Reserved. The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IQVIA or any of its affiliated or subsidiary entities.


The study was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number U54GM104942.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of West Virginia University’s Institutional Review Board (IRB) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

10557_2018_6825_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 13 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xue Feng
    • 1
  • Usha Sambamoorthi
    • 1
  • Kim Innes
    • 2
  • Gregory Castelli
    • 3
  • Traci LeMasters
    • 1
  • Lianjie Xiong
    • 4
  • Michael U. Williams
    • 5
  • Xi Tan
    • 1
    Email author
  1. 1.Department of Pharmaceutical Systems and Policy, School of PharmacyWest Virginia UniversityMorgantownUSA
  2. 2.Department of Epidemiology, School of Public HealthWest Virginia UniversityMorgantownUSA
  3. 3.University of Pittsburgh Medical Center (UPMC) St. MargaretPittsburghUSA
  4. 4.College of PharmacyCalifornia Health Sciences UniversityClovisUSA
  5. 5.Department of MedicineSan Antonio Military Medical CenterSan AntonioUSA

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