The Comparative Effectiveness and Safety of Direct Oral Anticoagulant (DOAC) and Warfarin Initiation in Adults with Atrial Fibrillation (AF) by eGFR Category
Bibliographic record
Abstract
Background: There is ongoing uncertainty regarding the risk-benefit ratio of DOACs in patients with AF and CKD. Methods: We conducted an international multicenter cohort study(2011-2018) using healthcare data from 5 jurisdictions across Australia (666 participants of the 45 and Up Study [among 267153 recruited in 2006-09] with data linked to hospital/laboratory data [by CHeReL] and the Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data provided by Services Australia; all linked data accessed via SURE) and Canada (73876 patients in AB,BC,MB,ON; record linkage of provincial administrative/laboratory data). We propensity score matched adults with a new dispensation of a DOAC (rivaroxaban, apixaban, dabigatran) or warfarin, who had AF and a recorded eGFR grouped as ≥60,45-59,30-44, <30ml/min/1.73m2. Chronic dialysis or kidney transplant recipients were excluded. We assessed 2 composite outcomes within 1 year of initiating either therapy: ischemic (all-cause death, ischemic stroke or TIA) and bleeding (intracranial, gastrointestinal or other). We used Cox regression to estimate the hazard ratios (HRs[95%CI]) of outcomes across eGFR categories and summarized centre data in random effects meta-analysis. Results: A total of 74542 eligible patients were included, among whom there were 6923(9.2%) ischemic and 1572(2.1%) bleeding events recorded. Across eGFR groups, DOAC initiation was associated with lower or similar risk for the ischemic outcome compared with warfarin initiation (pooled HRs[95%CI] for eGFR groups: 0.74[0.69-0.79], 0.76[0.54-1.07], 0.68[0.61-0.75] and 0.86[0.76-0.98], respectively). Similar results were observed for bleeding (0.75[0.65-0.86], 0.81[0.65-1.01], 0.82 [0.66-1.02], 0.71[0.52-0.99], respectively). There was no evidence of heterogeneity across jurisdictions except for eGFR 45-59ml/min/1.73m2 for the ischemic outcome (I2=77%). Conclusions: In this cohort of AF patients initiating DOAC or warfarin, compared to warfarin, DOAC use was associated with lower or similar risk of both ischemic and bleeding outcomes independent of eGFR. Our results suggest DOAC therapy may have a favourable risk-benefit ratio in AF patients with non-dialysis dependent CKD that is similar to that seen in AF patients with preserved kidney function. Adequately powered randomized trials are needed to confirm these findings. Funding: Government Support - Non-U.S.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.029 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.011 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".