International Journal of Clinical Pharmacy

, Volume 38, Issue 5, pp 1286–1293 | Cite as

A prospective study investigating the causes of warfarin under-utilization in Chinese patients

  • Shujuan Zhao
  • Hongwei Zhao
  • Xianpei Wang
  • Chuanyu Gao
  • Yuhua QinEmail author
  • Haixia Cai
  • Boya Chen
  • Jingjing Cao
Research Article


Background Warfarin is efficacious for ischemic stroke prevention in intermediate- to high-risk patients with atrial fibrillation; thus, warfarin is the recommended treatment according to evidence-based guidelines. Objective This prospective study evaluated the reasons for under-utilization of warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF). Setting The People’s Hospital of Henan Province of Zhengzhou City, which is a 3900-bed tertiary-care teaching institution. Methods We extracted data from an existing patient database. Patients at risk for thromboembolism were categorized based on CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 (doubled), diabetes, prior stroke (doubled), vascular disease, age 65–74 years, and sex category (female)] scores. Main outcome measure The percent of warfarin utilization was estimated in recruited patients. Any demographic and clinical factors associated with warfarin under-utilization were identified using a logistic regression model. Results Among the patient sample (n = 612), 569 patients had a CHA2DS2-VASc score of ≥1. At presentation, warfarin under-utilization was estimated to be 27.1 %. Only 120 patients (25.1 %) considered to be at the highest risk were prescribed warfarin. Binary logistic regression analysis indicated that previous stroke, age ≥75 years, and anti-platelet therapy were associated with warfarin under-utilization. Conclusion Patients with CHA2DS2-VASc scores ≥1 who were admitted with NVAF were under prescribed warfarin, and 138 patients were not treated with either warfarin or other antithrombotic therapies. In conclusion, a more aggressive approach for stroke prevention in NVAF patients is required.


Atrial fibrillation Atrial flutter China Prevention Stroke Warfarin 



The authors thank all patients, pharmacists, and physicians who contributed to the success of this work. We would also like to recognize Shijie Liang who performed statistical analysis. We thank the student interns who helped with data collection.



Conflicts of interest

The authors declare that they have no conflicts of interest concerning this article.


  1. 1.
    Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham study. Stroke. 1991;22(3):312–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Guo Y, Tian Y, Wang H, Si Q, Wang Y, Lip GY. Prevalence, incidence, and lifetime risk of atrial fibrillation in china: new insights into the global burden of atrial fibrillation. Chest. 2015;147(1):109–19.CrossRefPubMedGoogle Scholar
  3. 3.
    Stefansdottir H, Aspelund T, Gudnason V, Arnar DO. Trends in the incidence and prevalence of atrial fibrillation in Iceland and future projections. Europace. 2011;13(8):1110–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. Adult population. Am J Cardiol. 2013;112(8):1142–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):7s–47s.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.CrossRefPubMedGoogle Scholar
  7. 7.
    Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the esc guidelines for the management of atrial fibrillation: an update of the 2010 esc guidelines for the management of atrial fibrillation—developed with the special contribution of the european heart rhythm association. Europace. 2012;14(10):1385–413.CrossRefPubMedGoogle Scholar
  8. 8.
    Mega JL, Simon T. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments. Lancet. 2015;386(9990):281–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Frykman V, Beerman B, Ryden L, Rosenqvist M. Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications. Eur Heart J. 2001;22(20):1954–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation: developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47.CrossRefPubMedGoogle Scholar
  11. 11.
    Olsson SB, Halperin JL. Prevention of stroke in patients with atrial fibrillation. Semin Vasc Med. 2005;5(3):285–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Culebras A, Messe SR, Chaturvedi S, Kase CS, Gronseth G. Summary of evidence-based guideline update: prevention of stroke in nonvalvular atrial fibrillation—report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;82(8):716–24.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hu DY, Sun YH, Zhou ZQ, Li KB, Ni YB, Yang G, et al. Risk factors for stroke in chinese with non valvular atrial fibrillation: a case-control study. Zhonghua Nei Ke Za Zhi. 2003;42(3):157–61.PubMedGoogle Scholar
  14. 14.
    Aronis KN, Thigpen JL, Tripodis Y, Dillon C, Forster K, Henault L, et al. Paroxysmal atrial fibrillation and the hazards of under-treatment. Int J Cardiol. 2016;202:214–20.CrossRefPubMedGoogle Scholar
  15. 15.
    Go AS, Hylek EM, Borowsky LH, Phillips KA, Selby JV, Singer DE. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (atria) study. Ann Intern Med. 1999;131(12):927–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Tomita H, Okumura K, Inoue H, Atarashi H, Yamashita T, Origasa H, et al. Validation of risk scoring system excluding female sex from Cha2ds2-VASc in Japanese patients with nonvalvular atrial fibrillation: subanalysis of the j-rhythm registry. Circ J. 2015;79(8):1719–26.CrossRefPubMedGoogle Scholar
  17. 17.
    Hughes M, Lip GY. Guideline Development Group NCGfMoAFiP, Secondary Care NIfH, Clinical E. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost. 2008;99(2):295–304.PubMedGoogle Scholar
  18. 18.
    Pisters R, Lane DA, Marin F, Camm AJ, Lip GY. Stroke and thromboembolism in atrial fibrillation. Circ J. 2012;76(10):2289–304.CrossRefPubMedGoogle Scholar
  19. 19.
    Van Staa TP, Setakis E, Di Tanna GL, Lane DA, Lip GY. A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. J Thromb Haemost. 2011;9(1):39–48.CrossRefPubMedGoogle Scholar
  20. 20.
    Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167(13):1414–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Maki ED, Miesner AR, Grady SE, Marschall LM. Effects of depressive and other psychiatric disorders on anticoagulation control in a pharmacist-managed anticoagulation clinic. Ann Pharmacother. 2013;47(10):1292–300.CrossRefPubMedGoogle Scholar
  22. 22.
    Stafford L, van Tienen EC, Bereznicki LR, Peterson GM. The benefits of pharmacist-delivered warfarin education in the home. Int J Pharm Pract. 2012;20(6):384–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events. JAMA. 2006;296(15):1858–66.CrossRefPubMedGoogle Scholar
  24. 24.
    Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90(4):625–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Berg TM, O’Meara JG, Ou NN, Daniels PR, Moriarty JP, Bergstrahl EJ, et al. Risk factors for excessive anticoagulation among hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol. Pharmacotherapy. 2013;33(11):1165–74.CrossRefPubMedGoogle Scholar
  26. 26.
    Locke C, Ravnan SL, Patel R, Uchizono JA. Reduction in warfarin adverse events requiring patient hospitalization after implementation of a pharmacist-managed anticoagulation service. Pharmacotherapy. 2005;25(5):685–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the birmingham atrial fibrillation treatment of the aged study, bafta): a randomised controlled trial. Lancet. 2007;370(9586):493–503.CrossRefPubMedGoogle Scholar
  28. 28.
    Lee IH, Kim H, Je NK. Underutilization of warfarin for stroke prophylaxis in patients with atrial fibrillation or atrial flutter in Korea. J Cardiol. 2015;66(6):475–81.CrossRefPubMedGoogle Scholar
  29. 29.
    Sabouret P, Bricard M, Hermann MA, Cotte FE, Deret-Bixio L, Rushton-Smith S. Discrepancy between guidelines for stroke prevention in atrial fibrillation and practice patterns in primary care. The nationwide French AFIGP survey. Arch Cardiovasc Dis. 2015;108(11):544–53.CrossRefPubMedGoogle Scholar
  30. 30.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, 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
  31. 31.
    Harrington AR, Armstrong EP, Nolan PE Jr, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44:1676–81.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Shujuan Zhao
    • 1
  • Hongwei Zhao
    • 1
  • Xianpei Wang
    • 2
  • Chuanyu Gao
    • 2
  • Yuhua Qin
    • 1
    Email author
  • Haixia Cai
    • 1
  • Boya Chen
    • 1
  • Jingjing Cao
    • 1
  1. 1.Department of PharmacyPeople’s Hospital of Henan ProvinceZhengzhouChina
  2. 2.Department of Cardiovascular MedicinePeople’s Hospital of Henan ProvinceZhengzhouChina

Personalised recommendations