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Comparative Outcomes Between Direct Oral Anticoagulants, Warfarin, and Antiplatelet Monotherapy Among Chinese Patients with Atrial Fibrillation: A Population-Based Cohort Study

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Abstract

Introduction

Outcomes associated with suboptimal use of antithrombotic treatments (antiplatelets, warfarin, direct oral anticoagulants [DOACs]) are unclear in Chinese patients with atrial fibrillation (AF).

Objectives

Our objective was to assess the prescription patterns, quality, effectiveness, and safety of antithrombotic treatments.

Methods

This was a population-based cohort study using electronic health records in Hong Kong. Patients newly diagnosed with AF during 2010–2016 were followed up until 2017. Patients at high stroke risk (CHA2DS2-VASc score ≥ 2) and receiving antithrombotic treatments were matched using propensity scoring. We used Cox proportional hazards regression to compare the risks of ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between groups.

Results

Of the 52,178 high-risk patients with AF, 27,614 (52.9%) received antithrombotic treatment and were included in the analyses. Between 2010 and 2016, prescribing of antiplatelets and warfarin declined and that of DOACs increased dramatically (from 1 to 32%). Two-thirds of warfarin users experienced poor anticoagulation control. Warfarin and DOACs were associated with lower risks of ischemic stroke (warfarin, hazard ratio [HR] 0.51 [95% confidence interval (CI) 0.36–0.71]; DOACs, HR 0.69 [95% CI 0.51–0.94]) and all-cause mortality (warfarin, HR 0.47 [95% CI 0.39–0.57]; DOACs, HR 0.45 [95% CI 0.37–0.55]) than were antiplatelets. DOACs were associated with a lower risk of ICH than was warfarin (HR 0.53 [95% CI 0.34–0.83]). GIB risks were similar among all groups.

Conclusion

Antiplatelet prescribing and suboptimal warfarin management remain common in Chinese patients with AF at high risk of stroke. DOAC use may be associated with a lower risk of ischemic stroke and all-cause mortality when compared with antiplatelets and with a lower risk of ICH when compared with warfarin.

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References

  1. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, et al. 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. J Am Coll Cardiol. 2019;74:104–32.

    Article  PubMed  Google Scholar 

  2. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962.

    Article  Google Scholar 

  3. Huisman MV, Rothman KJ, Paquette M, Teutsch C, Diener H-C, Dubner SJ, et al. The changing landscape for stroke prevention in AF: findings from the GLORIA-AF Registry Phase 2. J Am Coll Cardiol. 2017;69:777–85.

    Article  PubMed  Google Scholar 

  4. Chiang C-E, Wang K-L, Lin S-J. Asian strategy for stroke prevention in atrial fibrillation. Europace. 2015;17:ii31–ii39.

    Article  PubMed  Google Scholar 

  5. Lip GY, Wang KL, Chiang CE. Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial fibrillation: time for a reappraisal. Int J Cardiol. 2015;180:246–54.

    Article  PubMed  Google Scholar 

  6. Sato H, Ishikawa K, Kitabatake A, Ogawa S, Maruyama Y, Yokota Y, et al. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke. 2006;37:447–51.

    Article  CAS  PubMed  Google Scholar 

  7. Siu CW, Lip GY, Lam KF, Tse HF. Risk of stroke and intracranial hemorrhage in 9727 Chinese with atrial fibrillation in Hong Kong. Heart Rhythm. 2014;11:1401–8.

    Article  PubMed  Google Scholar 

  8. Chan EW, Lau WCY, Siu CW, Lip GYH, Leung WK, Anand S, et al. Effect of suboptimal anticoagulation treatment with antiplatelet therapy and warfarin on clinical outcomes in patients with nonvalvular atrial fibrillation: a population-wide cohort study. Heart Rhythm. 2016;13:1581–8.

    Article  PubMed  Google Scholar 

  9. Chan EW, Lau WC, Leung WK, Mok MT, He Y, Tong TS, et al. Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology. 2015;149(586–95):e3.

    Article  Google Scholar 

  10. Lau WCY, Cheung C-L, Man KKC, Chan EW, Sing CW, Lip GYH, et al. Association between treatment with apixaban, dabigatran, rivaroxaban, or warfarin and risk for osteoporotic fractures among patients with atrial fibrillation. Ann Intern Med. 2020. https://doi.org/10.7326/M19-3671.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Law SWY, Lau WCY, Wong ICK, Lip GYH, Mok MT, Siu C-W, et al. Sex-based differences in outcomes of oral anticoagulation in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72:271–82.

    Article  CAS  PubMed  Google Scholar 

  12. Rassen JA, Shelat AA, Franklin JM, Glynn RJ, Solomon DH, Schneeweiss S. Matching by propensity score in cohort studies with three treatment groups. Epidemiology. 2013;24:401–9.

    Article  PubMed  Google Scholar 

  13. Lau WC, Chan EW, Cheung CL, Sing CW, Man KK, Lip GY, et al. Association between dabigatran vs. warfarin and risk of osteoporotic fractures among patients with nonvalvular atrial fibrillation. JAMA. 2017;317:1151–8.

    Article  CAS  PubMed  Google Scholar 

  14. McCaffrey DF, Griffin BA, Almirall D, Slaughter ME, Ramchand R, Burgette LF. A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med. 2013;32:3388–414.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Vallakati A, Lewis WR. Underuse of anticoagulation in patients with atrial fibrillation. Postgrad Med. 2016;128:191–200.

    Article  PubMed  Google Scholar 

  16. Wong CW. Anticoagulation for stroke prevention in elderly patients with non-valvular atrial fibrillation: what are the obstacles? Hong Kong Med J. 2016;22:608–15.

    Article  CAS  PubMed  Google Scholar 

  17. Hsu JC, Maddox TM, Kennedy K, Katz DF, Marzec LN, Lubitz SA, et al. Aspirin instead of oral anticoagulant prescription in atrial fibrillation patients at risk for stroke. J Am Coll Cardiol. 2016;67:2913–23.

    Article  CAS  PubMed  Google Scholar 

  18. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.

    Article  Google Scholar 

  19. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.

    Article  CAS  PubMed  Google Scholar 

  20. Ben Freedman S, Gersh BJ, Lip GY. Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation. Eur Heart J. 2015;36:653–6.

    Article  CAS  PubMed  Google Scholar 

  21. Marijon E, Le Heuzey JY, Connolly S, Yang S, Pogue J, Brueckmann M, et al. Causes of death and influencing factors in patients with atrial fibrillation: a competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study. Circulation. 2013;128:2192–201.

    Article  CAS  PubMed  Google Scholar 

  22. Mongkhon P, Naser AY, Fanning L, Tse G, Lau WCY, Wong ICK, et al. Oral anticoagulants and risk of dementia: a systematic review and meta-analysis of observational studies and randomized controlled trials. Neurosci Biobehav Rev. 2019;96:1–9.

    Article  CAS  PubMed  Google Scholar 

  23. Mongkhon P, Fanning L, Lau WCY, Tse G, Lau KK, Wei L, et al. Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: a population-based cohort study. Heart Rhythm. 2020;17:706–13.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Ms Lisa Lam and Mr Edmund Cheung, Department of Pharmacology and Pharmacy, University of Hong Kong, for proofreading this manuscript.

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Corresponding author

Correspondence to Wallis C. Y. Lau.

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Funding

This work was supported by the University of Hong Kong-University College London (HKU-UCL) Strategic Partnership Fund and an unconditional education grant from Pfizer Corporation Hong Kong Limited. The funders had no role in the study design, data collection and analysis, preparation of the manuscript, or decision to publish.

Availability of data and material

The datasets generated during and/or analysed during the current study are not publicly available because of the nature of sensitive electronic medical data. Code will be available upon request from the corresponding author.

Conflict of interest

EW Chan has received honoraria from the HA and research funding from The Hong Kong Research Grants Council; The Research Fund Secretariat of the Food and Health Bureau; the Narcotics Division of the Security Bureau of HKSAR, Hong Kong; the National Natural Science Fund of China, China; the Wellcome Trust, UK; Bayer; Bristol Myers Squibb; Pfizer, and Takeda for work unrelated to this study. ICK Wong has received research funding outside the submitted work from Bristol Myers Squibb, Janssen, Bayer, Novartis, GSK, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. X Li has received research grants from the Hong Kong Health and Medical Research Fund and Janssen and internal seed funding from the University of Hong Kong unrelated to this work. KKC Man received the CW Maplethorpe Fellowship and personal fees from IQVIA Holdings, Inc. (previously known as QuintilesIMS Holdings, Inc.) unrelated to this work. SP, VWSN, CWS, and WCYL have no conflicts of interests that are directly relevant to the content of this study.

Ethics approval

This study protocol was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference no. UW13-468).

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Li, X., Pathadka, S., Man, K.K.C. et al. Comparative Outcomes Between Direct Oral Anticoagulants, Warfarin, and Antiplatelet Monotherapy Among Chinese Patients with Atrial Fibrillation: A Population-Based Cohort Study. Drug Saf 43, 1023–1033 (2020). https://doi.org/10.1007/s40264-020-00961-0

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  • DOI: https://doi.org/10.1007/s40264-020-00961-0

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