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Comparative Study
. 2025 Jan 22;20(1):e0317895.
doi: 10.1371/journal.pone.0317895. eCollection 2025.

Comparative safety and effectiveness of oral anticoagulants in key subgroups of patients with non-valvular atrial fibrillation and at high risk of gastrointestinal bleeding: A cohort study based on the French National Health Data System (SNDS)

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
Comparative Study

Comparative safety and effectiveness of oral anticoagulants in key subgroups of patients with non-valvular atrial fibrillation and at high risk of gastrointestinal bleeding: A cohort study based on the French National Health Data System (SNDS)

Gregory Y H Lip et al. PLoS One. .

Abstract

Background: Risk factors and comorbidities can complicate management of non-valvular atrial fibrillation. We describe and compare real-world safety and effectiveness of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) and vitamin K antagonists (VKAs) in subgroups of patients with non-valvular atrial fibrillation at high risk for gastrointestinal (GI) bleeding, utilizing data from a national quasi-exhaustive French database.

Methods: Anticoagulant-naïve adults with non-valvular atrial fibrillation with ≥1 gastrointestinal bleeding risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. The following subgroups were evaluated: patients age ≥75 years, receiving concomitant medications, HAS-BLED score ≥3, and chronic kidney disease stage 3-4. Outcomes included major bleeding and stroke/systemic embolism. Patient characteristics were balanced using propensity score matching.

Results: A total of 314,184 patients were identified; characteristics were similar for propensity score-matched subgroups in VKA/DOAC and DOAC/DOAC comparisons. DOACs showed lower risk of major bleeding versus VKAs in all subgroups evaluated (p<0.0001 for all). Apixaban showed lower risk of major bleeding and gastrointestinal bleeding versus rivaroxaban in all subgroups (p≤0.05 for all) and versus dabigatran in elderly patients, patients with HAS-BLED score ≥3, and those receiving concomitant medications (p<0.05 for all). Stroke/systemic embolism risk was lower with apixaban versus rivaroxaban in elderly patients, those with HAS-BLED ≥3, and those receiving concomitant medications; risks were similar for other comparisons.

Conclusions: DOACs were associated with improved safety and effectiveness when compared to VKAs among subgroups of non-valvular atrial fibrillation patients at high risk of gastrointestinal bleeding. Apixaban was associated with lower risks of major bleeding, gastrointestinal bleeding, and stroke/systemic embolism versus rivaroxaban as well as lower risk of major bleeding, gastrointestinal bleeding bleed and similar risk of stroke/systemic embolism versus dabigatran among several of these patient subgroups.

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Conflict of interest statement

This was a BMS/Pfizer sponsored study. 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. 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. PS-matched hazard ratios among patients age ≥75 years for DOACs versus VKAs.
Fig 3
Fig 3. PS-matched hazard ratios among patients age ≥75 years for DOACs versus DOACs.
Fig 4
Fig 4. PS-matched hazard ratios among patients with HAS-BLED score ≥3 for DOACs versus VKAs.
Fig 5
Fig 5. PS-matched hazard ratios among patients with HAS-BLED score ≥3 for DOACs versus DOACs.
Fig 6
Fig 6. PS-matched hazard ratios among patients receiving concomitant antiplatelets, NSAIDs, or corticosteroids associated with GIB risk for DOACs versus VKAs.
Fig 7
Fig 7. PS-matched hazard ratios among patients receiving concomitant antiplatelets, NSAIDs, or corticosteroids associated with GIB risk for DOACs versus DOACs.
Fig 8
Fig 8. PS-matched hazard ratios among patients with CKD stage 3–4 for apixaban versus VKAs and rivaroxaban versus VKAs.
Fig 9
Fig 9. PS-matched hazard ratios among patients with CKD stage 3–4 for apixaban versus rivaroxaban.
See this image and copyright information in PMC

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