Adherence to Anticoagulation and Risk of Stroke Among Medicare Beneficiaries Newly Diagnosed with Atrial Fibrillation

  • Inmaculada HernandezEmail author
  • Meiqi He
  • Maria M. Brooks
  • Samir Saba
  • Walid F. Gellad
Original Research Article



The objective of this study was to compare the risk of stroke in atrial fibrillation (AF) with adherent use of oral anticoagulation (OAC), non-adherent use, and non-use of OAC.


Using 2013–2016 Medicare claims data, we identified patients newly diagnosed with AF in 2014–2015 and collected prescriptions filled for OAC in the 12 months after AF diagnosis (n = 39,272). We categorized participants each day into three time-dependent exposures: adherent use (≥ 80% of the previous 30 days covered with OAC), non-adherent use (0–80% covered with OAC), and non-use (0%). We constructed Cox proportional hazards models to estimate the association between time-dependent exposures and time to stroke, adjusting for demographics and clinical characteristics.


The sample included 39,272 patients. Study participants spent 35.0% of the follow-up period in the adherent use exposure category, 10.9% in the non-adherent category, and 54.0% in the non-use category. OAC adherent use [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.52–0.74] and non-adherent use (HR 0.74; 95% CI 0.57–0.95) were associated with lower hazards of stroke than non-use. Adherent use of DOAC (HR 0.54; 95% CI 0.42–0.69) and warfarin (HR 0.70; 95% CI 0.56–0.89) was associated with lower risk of stroke than non-use, but the risk of stroke did not statistically differ between DOAC and warfarin adherent use (HR 0.77; 95% CI 0.56–1.04).


Although adherence to OAC reduces stroke risk by nearly 40%, newly diagnosed AF patients in Medicare adhere to OAC on average only one third of the first year after AF diagnosis.



This work represents the opinions of the authors alone and does not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Compliance with Ethical Standards


This work was funded by the National Heart, Lung and Blood Institute (Grant number K01HL142847).

Conflict of interest

Saba has received research support from Boston Scientific. Hernandez has received advisory board fees from Pfizer. He, Brooks and Gellad declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Supplementary material

40256_2019_371_MOESM1_ESM.docx (55 kb)
Supplementary material 1 (DOCX 54 kb)


  1. 1.
    Hart RG, Halperin JL. Atrial fibrillation and stroke: concepts and controversies. Stroke. 2001;32(3):803–8.CrossRefPubMedGoogle Scholar
  2. 2.
    January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–104.CrossRefPubMedGoogle Scholar
  3. 3.
    Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med. 2010;123(7):638-645.e634.CrossRefGoogle Scholar
  4. 4.
    Lang K, Bozkaya D, Patel AA, et al. Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis. BMC Health Serv Res. 2014;14:329.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Kakkar AK, Mueller I, Bassand J-P, et al. International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD). Am Heart J. 2012;163(1):13-19.e11.CrossRefGoogle Scholar
  6. 6.
    Patel AA, Lennert B, Macomson B, et al. Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation. Am Health Drug Benefits. 2012;5(5):291–8.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Reynolds MR, Shah J, Essebag V, et al. Patterns and predictors of warfarin use in patients with new-onset atrial fibrillation from the FRACTAL Registry. Am J Cardiol. 2006;97(4):538–43.CrossRefPubMedGoogle Scholar
  8. 8.
    Ogilvie IM, Welner SA, Cowell W, Lip GY. Characterization of the proportion of untreated and antiplatelet therapy treated patients with atrial fibrillation. Am J Cardiol. 2011;108(1):151–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Alamneh EA, Chalmers L, Bereznicki LR. Suboptimal use of oral anticoagulants in atrial fibrillation: has the introduction of direct oral anticoagulants improved prescribing practices? Am J Cardiovasc Drugs. 2016;16(3):183–200.CrossRefPubMedGoogle Scholar
  10. 10.
    Hernandez I, Zhang Y, Saba S. Comparison of the effectiveness and safety of apixaban, dabigatran, rivaroxaban and warfarin in newly diagnosed atrial fibrillation. Am J Cardiol. 2017;120(10):1813–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Hernandez I, Saba S, Zhang Y. Geographic variation in the use of oral anticoagulation in stroke prevention in atrial fibrillation. Stroke. 48:2289–2291.Google Scholar
  12. 12.
    Marzec LN, Wang J, Shah ND, et al. Influence of direct oral anticoagulants on rates of oral anticoagulation for atrial fibrillation. J Am Coll Cardiol. 2017;69(20):2475–84.CrossRefPubMedGoogle Scholar
  13. 13.
    Hsu JC, Maddox TM, Kennedy KF, et al. Oral anticoagulant therapy prescription in patients with atrial fibrillation across the spectrum of stroke risk: insights from the NCDR PINNACLE Registry. JAMA Cardiol. 2016;1(1):55–62.CrossRefPubMedGoogle Scholar
  14. 14.
    Yao X, Abraham NS, Alexander GC, et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc 2016;5(2).Google Scholar
  15. 15.
    Borne RT, O’Donnell C, Turakhia MP, et al. Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the Veterans Health Administration. BMC Cardiovasc Disorders. 2017;17(1):236. Scholar
  16. 16.
    Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol. 2009;104(11):1534–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Crivera C, Nelson WW, Bookhart B, et al. Pharmacy quality alliance measure: adherence to non-warfarin oral anticoagulant medications. Curr Med Res Opin. 2015;31(10):1889–95. Scholar
  18. 18.
    Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse. 27 Chronic Condition Algorithm. Accessed April 26, 2017.Google Scholar
  19. 19.
    Kumamaru H, Judd SE, Curtis JR, et al. Validity of claims-based stroke algorithms in contemporary Medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with Medicare claims. Circ Cardiovasc Qual Outcomes. 2014;7(4):611–9.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Lo-Ciganic WH, Donohue JM, Jones BL, et al. Trajectories of diabetes medication adherence and hospitalization risk: a retrospective cohort study in a large state Medicaid program. J Gen Intern Med. 2016;31(9):1052–60. Scholar
  21. 21.
    Lo-Ciganic WH, Donohue JM, Thorpe JM, et al. Using machine learning to examine medication adherence thresholds and risk of hospitalization. Med Care. 2015;53(8):720–8.CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. 2016;5(6):e003725. Scholar
  23. 23.
    Zalesak M, Siu K, Francis K, et al. Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes. 2013;6(5):567–74.CrossRefPubMedGoogle Scholar
  24. 24.
    Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100.CrossRefPubMedGoogle Scholar
  26. 26.
    Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack. Stroke. 2017;48(8):2142–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Desai NR, Krumme AA, Schneeweiss S, et al. Patterns of initiation of oral anticoagulants in patients with atrial fibrillation—quality and cost implications. Am J Med. 2014;127(11):1075-1082.e1071.CrossRefGoogle Scholar
  28. 28.
    Hernandez I, Zhang Y, Brooks MM, Chin PK, Saba S. Anticoagulation use and clinical outcomes after major bleeding on dabigatran or warfarin in atrial fibrillation. Stroke. 2017;48(1):159–66.CrossRefPubMedGoogle Scholar
  29. 29.
    Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015;350:h1857.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Hernandez I, Baik SH, Pinera A, Zhang Y. Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med. 2015;175(1):18–24.CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Hernandez I, Zhang Y. Comparing stroke and bleeding with rivaroxaban and dabigatran in atrial fibrillation: analysis of the US Medicare Part D data. Am J Cardiovasc Drug. 2017;17(1):37–47.CrossRefGoogle Scholar
  32. 32.
    Gray M, Saba S, Zhang Y, Hernandez I. Outcomes of atrial fibrillation patients newly recommended for oral anticoagulation under the 2014 AHA/ACC/HRS guideline. J Am Heart Assn 7(1):e007881.Google Scholar
  33. 33.
    Hernandez I, Zhang Y, Saba S. Effectiveness and safety of direct oral anticoagulants and warfarin, stratified by stroke risk in patients with atrial fibrillation. Am J Cardiol. 2018;122(1):69–75.CrossRefPubMedGoogle Scholar
  34. 34.
    Peterson ED, Pokorney SD. New treatment options fail to close the anticoagulation gap in atrial fibrillation. J Am Coll Cardiol. 2017;69(20):2485–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Hess PL, Mirro MJ, Diener HC, et al. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012. Am Heart J. 2014;168(3):239-247.e231.CrossRefGoogle Scholar
  36. 36.
    Caro JJ. An economic model of stroke in atrial fibrillation: the cost of suboptimal oral anticoagulation. Am J Manag Care. 2004;10(14 Suppl):S451–8.PubMedGoogle Scholar
  37. 37.
    Patel AA, Ogden K, Veerman M, Mody SH, Nelson WW, Neil N. The economic burden to Medicare of stroke events in atrial fibrillation populations with and without thromboprophylaxis. Popul Health Manag. 2014;17(3):159–65.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Shrank WH, Patrick AR, Brookhart MA. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med. 2011;26(5):546–50.CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Andersohn F, Willich SN. The healthy adherer effect. Arch Intern Med. 2009;169(17):1633–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmacy and Therapeutics, School of PharmacyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Epidemiology, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  3. 3.Heart and Vascular InstituteUniversity of Pittsburgh Medical CentrePittsburghUSA
  4. 4.Division of General Internal Medicine, School of MedicineUniversity of PittsburghPittsburghUSA
  5. 5.VA Pittsburgh Healthcare SystemPittsburghUSA

Personalised recommendations