American Journal of Cardiovascular Drugs

, Volume 17, Issue 6, pp 475–479 | Cite as

Comparison of Prescribing Practices with Direct Acting Oral Anticoagulant Protocols

  • Evan Draper
  • Brandon Parkhurst
  • Blake Carley
  • Kori Krueger
  • Tonja Larson
  • Sara Griesbach
Original Research Article



The goal of anticoagulation management programs is to prevent thrombosis while minimizing the risks of hemorrhage. Direct acting oral anticoagulants (DOACs) selectively inhibit coagulation proteins to inhibit thrombosis. Previous studies suggest patient monitoring and education provided through anticoagulation services enhance adherence and decrease adverse outcomes in patients receiving DOAC therapy.


The objectives of this study were to describe DOAC prescribing adherence to anticoagulation service protocols and to observe whether enrollment in an anticoagulation service resulted in greater prescribing adherence to DOAC protocols.


A retrospective cohort study evaluated all initial prescriptions of apixaban, dabigatran, and rivaroxaban at Marshfield Clinic from 19 October 2010 to 21 August 2014. Three algorithms analyzed patient and prescription data extracted from the organization’s electronic health record and classified prescriptions as per protocol or not per protocol. The algorithms classified not per protocol prescriptions as off-label indication, renal impairment [estimated glomerular filtration rate (eGFR) <30 ml/min], hepatic impairment (rivaroxaban and apixaban), advanced age >74 years (dabigatran), dose too low, or dose too high. The analysis assessed whether enrollment in the Marshfield Clinic Anticoagulation Service DOAC monitoring process was associated with increased adherence to protocols.


In aggregate, 72% of apixaban prescriptions, 52% of dabigatran prescriptions, and 70% of rivaroxaban prescriptions were per protocol. Off-label indications and dosage too low were the most common not per protocol reasons for apixaban and rivaroxaban prescriptions. Age ≥75 years and off-label indication were the most common not per protocol reasons for dabigatran prescriptions. Enrollment in the anticoagulation service process was not associated with increased adherence to protocols.


A significant proportion of DOAC prescriptions did not adhere to protocol expectations. While enrollment in DOAC management through the Marshfield Clinic Anticoagulation Service was not associated with increased adherence to protocols, opportunities exist to optimize DOAC prescribing. Defining ideal DOAC management requires additional research.



The authors acknowledge Po-Huang Chyou, Ph.D., of the Marshfield Clinic Research Foundation for biostatistical assistance and Luanne Sojka of the Marshfield Clinic Pharmacy Administration for their contributions to this research. We further acknowledge the Marshfield Clinic Research Foundation’s Office of Scientific Writing and Publication for assistance in preparing this manuscript.

Compliance with ethical standards

Conflict of interest

Evan Draper, Brandon Parkhurst, Blake Carley, Kori Krueger, Tonja Larson, and Sara Griesbach declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria.

Ethical approval

This study was approved by the Marshfield Clinic Institutional Review Board.

Funding/financial support

This project was supported by the Marshfield Clinic Residency Research Committee.


  1. 1.
    Conway SE, Hwang AY, Ponte CD, Gums JG. Laboratory and clinical monitoring of direct acting oral anticoagulants: what clinicians need to know. Pharmacotherapy. 2017;37:236–48.CrossRefPubMedGoogle Scholar
  2. 2.
    Steinberg BA, Piccini JP. Anticoagulation in atrial fibrillation. BMJ. 2014;348:g2116.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Di Minno G, Russolillo A, Gambacorta C, Di Minno A, Prisco D. Improving the use of direct oral anticoagulants in atrial fibrillation. Eur J Intern Med. 2013;24:288–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Boehringer Ingelheim Pharmaceuticals, Inc. Prescribing information for Pradaxa (dabigatran etexilate mesylate) capsules, for oral use. November 2015.Google Scholar
  5. 5.
    Janssen Pharmaceuticals, Inc. Prescribing information for Xarelto (rivaroxaban) tablets, for oral use. September 2015.Google Scholar
  6. 6.
    Bristol-Myers Squibb Company. Prescribing information for Eliquis (apixaban) tablets, for oral use. June 2015.Google Scholar
  7. 7.
    Carley B, Griesbach S, Larson T, Krueger K. Assessment of dabigatran utilization and prescribing patterns for atrial fibrillation in a physician group practice setting. Am J Cardiol. 2014;113:650–4.CrossRefPubMedGoogle Scholar
  8. 8.
    American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatric Soc. 2012;60:616–31.CrossRefGoogle Scholar
  9. 9.
    Micromedex 2.0 Apixaban Drug Point Summary. Truven Analytics. 2014. Accessed 18 Oct 2016.
  10. 10.
    Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, Bradley SM, Maddox TM, Grunwald GK, Barón AE, Rumsfeld JS, Varosy PD, Schneider PM, Marzec LN, Ho PM. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the Veterans Health Administration. Am Heart J. 2014;167:810–7.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fitch K, Broulette J, Kwong WJ. The economic burden of ischemic stroke and major hemorrhage in Medicare beneficiaries with nonvalvular atrial fibrillation: a retrospective claims analysis. Am Health Drug Benefits. 2014;7:200–9.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Ghate SR, Biskupiak J, Ye X, Kwong WJ, Brixner DI. All-cause and bleeding-related health care costs in warfarin-treated patients with atrial fibrillation. J Manag Care Pharm. 2011;17:672–84.PubMedGoogle Scholar
  13. 13.
    Lee PY, Han SY, Miyahara RK. Adherence and outcomes of patients treated with dabigatran: Pharmacist-managed anticoagulation clinic versus usual care. Am J Health Syst Pharm. 2013;70:1154–61.CrossRefPubMedGoogle Scholar
  14. 14.
    Chan LL, Crumpler WL, Jacobson AK. Implementation of pharmacist-managed anticoagulation in patients receiving newer anticoagulants. Am J Health Syst Pharm. 2013;70(1285–6):1288.Google Scholar
  15. 15.
    Schulman S, Shortt B, Robinson M, Eikelboom JW. Adherence to anticoagulant treatment with dabigatran in a real-world setting. J Thromb Haemost. 2013;11:1295–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol. 2017;69:2779–90.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Evan Draper
    • 1
  • Brandon Parkhurst
    • 2
  • Blake Carley
    • 1
  • Kori Krueger
    • 2
  • Tonja Larson
    • 1
  • Sara Griesbach
    • 1
  1. 1.Clinical Pharmacy ServicesMarshfield ClinicMarshfieldUSA
  2. 2.Institute for Quality, Innovation, and Patient SafetyMarshfield ClinicMarshfieldUSA

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