Skip to main content
SpringerLink
Log in

Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis

  • REVIEW ARTICLE
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background

Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting.

Methods

We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF.

Results

From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63–0.78]), acute myocardial infarction (0.67; [0.57–0.79]), all-cause mortality (0.62; [0.56–0.69]), major bleeding (0.59; [0.50–0.69]), intracranial hemorrhage (0.50; [0.40–0.62]), gastrointestinal bleeding (0.66; [0.46–0.95]), and any bleeding (0.82; [0.73–0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs.

Conclusions

The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Lip GYH, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial fibrillation: past, present and future. Thromb Haemost. 2017;117(7):1230–9.

    Article  Google Scholar 

  2. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–62.

    Article  CAS  Google Scholar 

  3. Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol. 2007;50(4):309–15.

    Article  Google Scholar 

  4. 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  Google Scholar 

  5. Wang KL, Lip GY, Lin SJ, Chiang CE. Non-vitamin K antagonist oral anticoagulants for stroke prevention in Asian patients with nonvalvular atrial fibrillation: meta-analysis. Stroke. 2015;46(9):2555–61.

    Article  CAS  Google Scholar 

  6. Freedman B, Potpara TS, Lip GY. Stroke prevention in atrial fibrillation. Lancet. 2016;388(10046):806–17.

    Article  Google Scholar 

  7. Cho MS, Yun JE, Park JJ, Kim YJ, Lee J, Kim H et al. Outcomes after use of standard- and low-dose non-vitamin K oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2018:STROKEAHA118023093.

  8. Chan YH, See LC, Tu HT, Yeh YH, Chang SH, Wu LS et al. Efficacy and safety of apixaban, dabigatran, rivaroxaban, and warfarin in Asians with nonvalvular atrial fibrillation. J Am Heart Assoc. 2018;7(8).

  9. Kohsaka S, Katada J, Saito K, Terayama Y. Safety and effectiveness of apixaban in comparison to warfarin in patients with nonvalvular atrial fibrillation: a propensity-matched analysis from Japanese administrative claims data. Curr Med Res Opin. 2018;34(9):1627–34.

    Article  CAS  Google Scholar 

  10. Kohsaka S, Murata T, Izumi N, Katada J, Wang F, Terayama Y. Bleeding risk of apixaban, dabigatran, and low-dose rivaroxaban compared with warfarin in Japanese patients with non-valvular atrial fibrillation: a propensity matched analysis of administrative claims data. Curr Med Res Opin. 2017;33(11):1955–63.

    Article  CAS  Google Scholar 

  11. Chan YH, Lee HF, See LC, Tu HT, Chao TF, Yeh YH, et al. Effectiveness and safety of four direct oral anticoagulants in Asians with non-valvular atrial fibrillation. Chest. 2019.

  12. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–41.

    Article  Google Scholar 

  13. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.

    Article  CAS  Google Scholar 

  14. Bai Y, Deng H, Shantsila A, Lip GY. Rivaroxaban versus dabigatran or warfarin in real-world studies of stroke prevention in atrial fibrillation: systematic review and meta-analysis. Stroke. 2017;48(4):970–6.

    Article  CAS  Google Scholar 

  15. Cha MJ, Choi EK, Han KD, Lee SR, Lim WH, Oh S, et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017;48(11):3040–8.

    Article  CAS  Google Scholar 

  16. Ho JC, Chang AM, Yan BP, Yu CM, Lam YY, Lee VW. Dabigatran compared with warfarin for stroke prevention with atrial fibrillation: experience in Hong Kong. Clin Cardiol. 2012;35(12):E40–5.

    Article  Google Scholar 

  17. Li WH, Huang D, Chiang CE, Lau CP, Tse HF, Chan EW, et al. Efficacy and safety of dabigatran, rivaroxaban, and warfarin for stroke prevention in Chinese patients with atrial fibrillation: the Hong Kong Atrial Fibrillation Project. Clin Cardiol. 2017;40(4):222–9.

    Article  Google Scholar 

  18. Chan PH, Huang D, Hai JJ, Li WH, Yin LX, Chan EW, et al. Stroke prevention using dabigatran in elderly Chinese patients with atrial fibrillation. Heart Rhythm. 2016;13(2):366–73.

    Article  Google Scholar 

  19. Lau WCY, Li X, Wong ICK, Man KKC, Lip GYH, Leung WK, et al. Bleeding-related hospital admissions and 30-day readmissions in patients with non-valvular atrial fibrillation treated with dabigatran versus warfarin. J Thromb Haemost. 2017;15(10):1923–33.

    Article  CAS  Google Scholar 

  20. Lee KH, Park HW, Lee N, Hyun DY, Won J, Oh SS, et al. Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation. Europace. 2017;19(suppl_4):iv1–9.

    Article  Google Scholar 

  21. Naganuma M, Shiga T, Nagao T, Suzuki A, Murasaki K, Hagiwara N. Effectiveness and safety of dabigatran versus warfarin in “real-world” Japanese patients with atrial fibrillation: a single-center observational study. J Arrhythm. 2017;33(2):107–10.

    Article  Google Scholar 

  22. Chan LXWY, Chia PL, Kek ZL. A single institution’s experience with using dabigatran, rivaroxaban and warfarin for prevention of thromboembolism in atrial fibrillation. PoSH. 2018;27(1):20–5.

    Article  Google Scholar 

  23. Wee XT, Ho LM, Ho HK, Lee JY, Yap CW, William H, et al. Incidence of thromboembolic and bleeding events in patients with newly diagnosed nonvalvular atrial fibrillation: an Asian multicenter retrospective cohort study in Singapore. Clin Cardiol. 2017;40(12):1218–26.

    Article  Google Scholar 

  24. Lau WCY, Chan EW, Wong ICK. Dabigatran versus warfarin in patients with non-valvular atrial fibrillation: a population-wide cohort study in chinese patients. Pharmacoepidemiol Drug Saf. 2016;25(Supplement 3):282.

    Google Scholar 

  25. Koretsune Y, Yamashita T, Yasaka M, Ono Y, Hirakawa T, Ishida K, et al. Comparative effectiveness and safety of warfarin and dabigatran in patients with non-valvular atrial fibrillation in Japan: a claims database analysis. J Cardiol. 2019;73(3):204–9.

    Article  Google Scholar 

  26. Mao L, Li C, Li T, Yuan K. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in Chinese patients with atrial fibrillation. Vascular. 2014;22(4):252–8.

    Article  CAS  Google Scholar 

  27. Jeong HK, Lee KH, Park HW, Yoon NS, Kim MC, Lee N, et al. Real world comparison of rivaroxaban and warfarin in Korean patients with atrial fibrillation: propensity matching cohort analysis. Chonnam Med J. 2019;55(1):54–61.

    Article  Google Scholar 

  28. Yu HT, Yang PS, Kim TH, Jang E, Kim D, Uhm JS, et al. Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation. Stroke. 2018;49(10):2421–9.

    Article  CAS  Google Scholar 

  29. Lee CJ, Gerds TA, Carlson N, Bonde AN, Gislason GH, Lamberts M, et al. Risk of myocardial infarction in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(1):17–26.

    Article  Google Scholar 

  30. Weijs B, Blaauw Y, Rennenberg RJ, Schurgers LJ, Timmermans CC, Pison L, et al. Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J. 2011;32(20):2555–62.

    Article  CAS  Google Scholar 

  31. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008;100(4):593–603.

    CAS  PubMed  Google Scholar 

  32. Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2017;48(9):2494–503.

    Article  CAS  Google Scholar 

  33. Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975–83.

    Article  CAS  Google Scholar 

  34. Singer DE, Hellkamp AS, Piccini JP, Mahaffey KW, Lokhnygina Y, Pan G, et al. Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. J Am Heart Assoc. 2013;2(1):e000067.

  35. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.

    Article  CAS  Google Scholar 

  36. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J-ROCKET AF study. Circ J. 2012;76(9):2104–11.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by grants 105-2628-B-182A-003-MY3 from the Ministry of Science and Technology and CMRPG3E0291 from the Chang Gung Memorial Hospital, Linkou, Taiwan.

Author information

Authors and Affiliations

  1. The Cardiovascular Department, Chang Gung Memorial Hospital, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan

    Yi-Hsin Chan, Hsin-Fu Lee, Chia-Tung Wu, Shang-Hung Chang, Yung-Hsin Yeh, Chi-Tai Kuo, Pao-Hsien Chu & Chun-Li Wang

  2. College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan

    Yi-Hsin Chan, Hsin-Fu Lee, Chia-Tung Wu, Shang-Hung Chang, Yung-Hsin Yeh, Chi-Tai Kuo, Pao-Hsien Chu & Chun-Li Wang

  3. Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan

    Yi-Hsin Chan

  4. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Hsin-Fu Lee

  5. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Tze-Fan Chao

  6. Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan

    Tze-Fan Chao

  7. Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan

    Lai-Chu See

  8. Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan

    Lai-Chu See

  9. Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan

    Lai-Chu See

  10. Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK

    Gregory Y. H. Lip

Authors
  1. Yi-Hsin Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsin-Fu Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tze-Fan Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chia-Tung Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shang-Hung Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yung-Hsin Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lai-Chu See
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chi-Tai Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pao-Hsien Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chun-Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gregory Y. H. Lip
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chun-Li Wang or Gregory Y. H. Lip.

Ethics declarations

Disclosures

GYHL: Consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. The remaining authors have nothing to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 5.21 MB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chan, YH., Lee, HF., Chao, TF. et al. Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis. Cardiovasc Drugs Ther 33, 701–710 (2019). https://doi.org/10.1007/s10557-019-06910-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-019-06910-z

Keywords

Search

Navigation