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Published on: February 26, 2013
Bleeding Risk of Direct Oral Anticoagulants in Patients With Heart Failure And Atrial Fibrillation
Cynthia A Jackevicius1,2,3,4, Lingyun Lu1, Zunera Ghaznavi5,6
1Department of Pharmacy (C.A.J., L.L.), Veterans Affairs Greater Los Angeles Healthcare System, CA.
Insights
Direct oral anticoagulants (DOACs) showed lower bleeding and death rates than warfarin in heart failure patients with atrial fibrillation. Close monitoring of renal function and dose adjustments are crucial for DOAC safety.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
Background:
- Direct oral anticoagulants (DOACs) use in heart failure patients with atrial fibrillation requires further real-world investigation.
- Renal dysfunction is common in heart failure, potentially increasing bleeding risk with DOACs compared to warfarin.
Purpose of the Study:
- To evaluate the real-world effectiveness and safety of DOACs versus warfarin in patients with heart failure and atrial fibrillation.
- To assess the impact of renal function on outcomes in this patient subgroup.
Main Methods:
- Retrospective cohort study using linked Veterans Administration databases.
- Included patients with heart failure newly started on warfarin or DOACs for atrial fibrillation (Oct 2010-Aug 2017).
- Outcomes analyzed included bleeding, stroke, and death using Cox models with inverse probability of treatment weighting.
Main Results:
- DOACs were associated with significantly lower rates of total bleeding, major bleeding, and death compared to warfarin.
- Apixaban and dabigatran showed benefits, but rivaroxaban did not demonstrate significant differences in bleeding or death.
- Moderate/severe chronic kidney disease was prevalent; renal function decline increased bleeding risk with DOACs, necessitating dose adjustments.
Conclusions:
- DOACs, particularly apixaban and dabigatran, are associated with reduced bleeding and mortality versus warfarin in heart failure patients with atrial fibrillation, irrespective of renal function.
- Renal function decline with DOAC use increases bleeding risk, highlighting the importance of monitoring and dose adjustments.
- Pharmacist or anticoagulation clinic management was linked to better outcomes, suggesting improved adherence and monitoring.
Background:
Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin.
Methods:
We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting.
Results:
Total bleeding (hazard ratio, 0.62 [95% CI, 0.56-0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40-0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71-0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing.
Conclusions:
DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.
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