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

PLoS One. 2024 Nov 15;19(11):e0310322. doi: 10.1371/journal.pone.0310322. eCollection 2024.

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.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / adverse effects
  • Anticoagulants* / therapeutic use
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Cohort Studies
  • Dabigatran* / administration & dosage
  • Dabigatran* / adverse effects
  • Dabigatran* / therapeutic use
  • Female
  • France / epidemiology
  • Gastrointestinal Hemorrhage* / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Risk Factors
  • Rivaroxaban* / administration & dosage
  • Rivaroxaban* / adverse effects
  • Rivaroxaban* / therapeutic use
  • Stroke / epidemiology
  • Stroke / etiology
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Rivaroxaban
  • Dabigatran
  • Pyridones
  • apixaban
  • Pyrazoles
  • Vitamin K

Grants and funding

This study was supported by funding from Bristol Myers Squibb/Pfizer sponsored awarded to all authors. Additionally, medical writing support was funded by Bristol Myers Squibb/Pfizer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.