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

  • Yi-Hsin Chan
  • Hsin-Fu Lee
  • Tze-Fan Chao
  • Chia-Tung Wu
  • Shang-Hung Chang
  • Yung-Hsin Yeh
  • Lai-Chu See
  • Chi-Tai Kuo
  • Pao-Hsien Chu
  • Chun-Li WangEmail author
  • Gregory Y. H. LipEmail author
REVIEW ARTICLE

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.

Keywords

Atrial fibrillation Direct thrombin inhibitor Factor Xa inhibitor Ischemic stroke Hemorrhage Mortality Warfarin 

Notes

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.

Compliance with Ethical Standards

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.

Supplementary material

10557_2019_6910_MOESM1_ESM.doc (5.2 mb)
ESM 1 (DOC 5.21 MB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yi-Hsin Chan
    • 1
    • 2
    • 3
  • Hsin-Fu Lee
    • 1
    • 2
    • 4
  • Tze-Fan Chao
    • 5
    • 6
  • Chia-Tung Wu
    • 1
    • 2
  • Shang-Hung Chang
    • 1
    • 2
  • Yung-Hsin Yeh
    • 1
    • 2
  • Lai-Chu See
    • 7
    • 8
    • 9
  • Chi-Tai Kuo
    • 1
    • 2
  • Pao-Hsien Chu
    • 1
    • 2
  • Chun-Li Wang
    • 1
    • 2
    Email author
  • Gregory Y. H. Lip
    • 10
    Email author
  1. 1.The Cardiovascular Department, Chang Gung Memorial HospitalTaoyuan CityTaiwan
  2. 2.College of MedicineChang Gung UniversityTaoyuanTaiwan
  3. 3.Microscopy Core Laboratory, Chang Gung Memorial HospitalTaoyuanTaiwan
  4. 4.Graduate Institute of Clinical Medical Sciences, College of MedicineChang Gung UniversityTaoyuanTaiwan
  5. 5.Division of Cardiology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  6. 6.Institute of Clinical Medicine, Cardiovascular Research CenterNational Yang-Ming UniversityTaipeiTaiwan
  7. 7.Department of Public Health, College of MedicineChang Gung UniversityTaoyuanTaiwan
  8. 8.Biostatistics Core Laboratory, Molecular Medicine Research CenterChang Gung UniversityTaoyuanTaiwan
  9. 9.Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial HospitalTaoyuanTaiwan
  10. 10.Liverpool Centre for Cardiovascular ScienceUniversity of Liverpool and Liverpool Heart & Chest HospitalLiverpoolUK

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