Real-world study of direct oral anticoagulant dosing patterns in patients with atrial fibrillation

Main Article Content

Keywords

Anticoagulants, Thromboembolism, Atrial Fibrillation, Stroke, Off-Label Use, Drug-Related Side Effects and Adverse Reactions, Patient Outcome Assessment, Retrospective Studies, United States

Abstract

Background: Direct oral anticoagulants (DOACs) are preferred for stroke prevention in atrial fibrillation (AF). However, off-label doses have been associated with increased risk of adverse events.


Objective: The objective of this study was to compare the frequency and outcomes of labeled versus off-label DOAC dosing in patients with AF.


Methods: This retrospective cohort study included adults diagnosed with nonvalvular AF (NVAF), discharged from University of Utah Health on DOAC therapy between 7/1/2017 and 9/30/2017. The primary outcome was off-label DOAC dosing frequency, defined as dosing inconsistent with manufacturer labeling. Secondary outcomes included variables associated with off-label dosing and a composite of adverse events (major bleeding, thromboembolism, and all-cause mortality) in the 90 days following the index hospital discharge.


Results: Of 249 included patients, 16.1% were discharged with off-label dosing. Factors associated with off-label dosing included advanced age, lower body mass index, decreased renal function, use of rivaroxaban, and hepatic impairment. The majority of off-label patients (70%) received lower-than-recommended DOAC dosing. Prescriber rationale for off-label prescribing was documented in 25% of patients and included anti-Xa guided dosing, high risk for bleeding or thromboembolism, and prior history of on-therapy adverse events. The rate of adverse events between labeled and off-label DOAC doses was not statistically different (10.0% vs. 6.7%, p=0.299), although this is likely due to small sample size.


Conclusions: Off-label DOAC prescribing for stroke prevention in NVAF at University of Utah Health was consistent or lower than previously published studies. Off-label dosing most often involved under-dosing of rivaroxaban. Future research should investigate the role of provider rationale and insight in optimizing DOAC therapy outcomes.

Abstract 714 | pdf Downloads 327

References

1. Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, Kowey PR, Mahaffey KW, Naccarelli G, Reiffel J, Singer DE, Peterson ED, Piccini JP, ORBIT-AF Investigators and Patients. Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes: The ORBIT-AF II Registry. J Am Coll Cardiol. 2016;68(24):2597-2604. https://doi.org/10.1016/j.jacc.2016.09.966
2. Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, Lo-Ciganic WH. Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses. Clin Ther. 2017;39(7):1456-1478. https://doi.org/10.1016/j.clinthera.2017.05.358
3. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, Jr., Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2019;16(8):e66-e93. https://doi.org/10.1016/j.hrthm.2019.01.024
4. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, Lane DA, Ruff CT, Turakhia M, Werring D, Patel S, Moores L. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018;154(5):1121-1201. https://doi.org/10.1016/j.chest.2018.07.040
5. Eliquis(R) [Package Insert]. Princeton, NJ: Bristol-Myers Squibb Company; (2017). https://www.eliquis.bmscustomerconnect.com/ (acessed Sep 30, 2017).
6. Xarelto(R) [Package Insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; (2017). https://www.xarelto-us.com/ (acessed Sep 30, 2017).
7. Pradaxa(R) [Package Insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; (2017). https://www.pradaxa.com/ (acessed Sep 30, 2017).
8. Whitworth MM, Haase KK, Fike DS, Bharadwaj RM, Young RB, MacLaughlin EJ. Utilization and prescribing patterns of direct oral anticoagulants. Int J Gen Med. 2017;10:87-94. https://doi.org/10.2147/ijgm.s129235
9. Howard M, Lipshutz A, Roess B, Hawes E, Deyo Z, Burkhart JI, Moll S, Shilliday BB. Identification of risk factors for inappropriate and suboptimal initiation of direct oral anticoagulants. J Thromb Thrombolysis. 2017;43(2):149-156. https://doi.org/10.1007/s11239-016-1435-3
10. Saunders JA, Gustafson WL, Vazquez SR, Jones AE, Witt DM. Real-world assessment of off-label direct oral anticoagulant dosing for venous thromboembolism. J Thromb Thrombolysis. 2019;48(3):506-510. https://doi.org/10.1007/s11239-019-01904-y
11. Gibson CM, Smith CB, Davis S, Scalese MJ. Assessment of Apixaban Prescribing Patterns for Nonvalvular Atrial Fibrillation in Hospitalized Patients. Ann Pharmacother. 2018;52(1):54-59. https://doi.org/10.1177/1060028017726795
12. Arbel R, Sergienko R, Hammerman A, Greenberg-Dotan S, Batat E, Avnery O, Ellis MH. Effectiveness and Safety of Off-Label Dose-Reduced Direct Oral Anticoagulants in Atrial Fibrillation. Am J Med. 2019;132(7):847-855. https://doi.org/10.1016/j.amjmed.2019.01.025
13. Barra ME, Fanikos J, Connors JM, Sylvester KW, Piazza G, Goldhaber SZ. Evaluation of Dose-Reduced Direct Oral Anticoagulant Therapy. Am J Med. 2016;129(11):1198-1204. https://doi.org/10.1016/j.amjmed.2016.05.041
14. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381. https://doi.org/10.1016/j.jbi.2008.08.010
15. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN, REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. https://doi.org/10.1016/j.jbi.2019.103208
16. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-694. https://doi.org/10.1111/j.1538-7836.2005.01204.x