Comparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort Study.

Abstract

BACKGROUND:

The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear.

METHODS:

We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders.

RESULTS:

Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46-0.90]) or apixaban (HR, 0.40 [95% CI, 0.19-0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47-1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91-3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58-0.82]), apixaban (HR, 0.60 [95% CI, 0.46-0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62-1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18-2.14]).

CONCLUSIONS:

Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

• Authors: Oluwadolapo D Lawal, Herbert D Aronow, Fisayomi Shobayo, Anne L Hume, Tracey H Taveira, Kelly L Matson, Yichi Zhang, Xuerong Wen
• Journal: Circulation (Circulation) Vol. 147 Issue 10 Pg. 782-794 (03 07 2023) ISSN: 1524-4539 [Electronic] United States
• PMID: 36762560 (Publication Type: Journal Article)

Chemical References

• Warfarin
• Rivaroxaban
• Anticoagulants
• Dabigatran

Topics

• Humans
• Warfarin (adverse effects)
• Atrial Fibrillation (diagnosis, drug therapy, epidemiology)
• Rivaroxaban (adverse effects)
• Anticoagulants (adverse effects)
• Cohort Studies
• Retrospective Studies
• Stroke (epidemiology, prevention & control, drug therapy)
• Hemorrhage (chemically induced, epidemiology, drug therapy)
• Dabigatran (adverse effects)
• Liver Diseases (diagnosis, epidemiology)
• Embolism (epidemiology, prevention & control, complications)
• Ischemic Stroke
• Administration, Oral