Bleeding Risk of Direct Oral Anticoagulants in Patients With Heart Failure And Atrial Fibrillation
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".