Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Nov 15;19(11):e0310322.
doi: 10.1371/journal.pone.0310322. eCollection 2024.

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study

Gregory Y H Lip  1   2 , Robert Benamouzig  3 , Anne-Céline Martin  4   5 , Giancarlo Pesce  6 , Gaelle Gusto  7 , Nadia Quignot  7 , Artak Khachatryan  8 , Feng Dai  9 , Fouad Sedjelmaci  10 , Jose Chaves  11 , Rupesh Subash  12 , Ruth Mokgokong  12
Affiliations
Observational Study

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study

Gregory Y H Lip et al. PLoS One. .

Abstract

Background: This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB).

Methods: Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching.

Results: A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all).

Conclusions: DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran.

PubMed Disclaimer

Conflict of interest statement

GYHL reported serving as a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos outside the submitted work. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 899871. RB reported serving as a consultant for Alfasigma, Medtronic, Falk, Mayoli and Pfizer. ACM reported serving as a consultant and speaker for Abbott, Bayer, BMS/Pfizer, Boehringer Ingelheim, and received research grant from BMS/Pfizer. GP, GG, AK and NQ are employees of Certara, who were paid consultants to Pfizer and Bristol Myers Squibb in connection with the conduct of this study. FD, FS, JC, RS and RM are employees and shareholders of Pfizer. We confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Patient selection criteria.
Fig 2
Fig 2. Kaplan-Meier curves for MB.
Apixaban versus VKAs (A), dabigatran versus VKAs (B), rivaroxaban versus VKAs (C), rivaroxaban versus apixaban (D), dabigatran versus apixaban (E), and dabigatran versus rivaroxaban (F).
Fig 3
Fig 3. Kaplan-Meier curves for GIB.
Apixaban versus VKAs (A), dabigatran versus VKAs (B), rivaroxaban versus VKAs (C), rivaroxaban versus apixaban (D), dabigatran versus apixaban (E), and dabigatran versus rivaroxaban (F).
Fig 4
Fig 4. Kaplan-Meier curves for stroke/SE.
Apixaban versus VKAs (A), dabigatran versus VKAs (B), rivaroxaban versus VKAs (C), rivaroxaban versus apixaban (D), dabigatran versus apixaban (E), and dabigatran versus rivaroxaban (F).
Fig 5
Fig 5. PS-matched hazard ratios for DOACs versus VKAs.
Apixaban (A), dabigatran (B), and rivaroxaban (C).
Fig 6
Fig 6. PS-matched hazard ratios for DOACs versus DOACs.
Apixaban versus dabigatran (A), dabigatran versus rivaroxaban (B), and apixaban versus rivaroxaban (C).
Fig 7
Fig 7. PS-matched hazard ratios for subgroup analyses of DOACs versus VKAs.
Standard dose of apixaban (A), dabigatran (B), and rivaroxaban (C) and reduced dose of apixaban (D), dabigatran (E), and rivaroxaban (F).
Fig 8
Fig 8. PS-matched hazard ratios for subgroup analyses of DOACs versus DOACs.
Standard dose of apixaban versus dabigatran (A), dabigatran versus rivaroxaban (B), and apixaban versus rivaroxaban (C) and reduced dose of apixaban versus dabigatran (D), dabigatran versus rivaroxaban (E), and apixaban versus rivaroxaban (F).
See this image and copyright information in PMC

References

    1. Chao TF, Joung B, Takahashi Y, Lim TW, Choi EK, Chan YH, et al.. 2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary. Thromb Haemost. 2022;122(1):20–47. Epub 2021/11/14. doi: 10.1055/s-0041-1739411 ; PubMed Central PMCID: PMC8763451. - DOI - PMC - PubMed
    1. Wang YP, Kehar R, Iansavitchene A, Lazo-Langner A. Bleeding Risk in Nonvalvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies. TH Open. 2020;4(3):e145–e52. Epub 2020/07/18. doi: 10.1055/s-0040-1714918 ; PubMed Central PMCID: PMC7358046. - DOI - PMC - PubMed
    1. Chowdhury KR, Michaud J, Yu OHY, Yin H, Azoulay L, Renoux C. Effectiveness and Safety of Apixaban versus Rivaroxaban in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus. Thromb Haemost. 2022;122(10):1794–803. Epub 2022/03/17. doi: 10.1055/a-1798-2116 . - DOI - PubMed
    1. Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, et al.. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021;23(10):1612–76. Epub 2021/04/26. doi: 10.1093/europace/euab065 . - DOI - PMC - PubMed
    1. 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. Epub 2013/12/10. doi: 10.1016/S0140-6736(13)62343-0 . - DOI - PubMed

Publication types

MeSH terms