Early vs Delayed Direct Oral Anticoagulant (DOAC) Resumption After Ischemic Stroke in Patients with Atrial Fibrillation: A MetaAnalysis
Bibliographic record
Abstract
Background: For patients with atrial fibrillation (AF) who experience acute ischemic stroke, clinicians must balance prevention of early recurrent embolism against the risk of intracranial hemorrhage (ICH) when restarting direct oral anticoagulants (DOACs). The optimal timing for DOAC resumption remains uncertain. Methods: We conducted a systematic review and meta-analysis (PRISMA-aligned) of randomized controlled trials, registry-based randomized trials, and prospective cohorts comparing early versus delayed DOAC initiation after ischemic stroke in adults with AF. Databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library) were searched from inception to June 2024. Two reviewers performed independent screening, data extraction, and risk-of-bias assessment (RoB 2.0 for RCTs; Newcastle–Ottawa Scale for the cohort). Random-effects models (DerSimonian–Laird) were prespecified for pooled analyses; heterogeneity was assessed with I² and χ². Primary outcomes were recurrent ischemic stroke and ICH; secondary outcomes included major bleeding, all-cause mortality, and composite endpoints. Results: Three studies (n = 4028) met eligibility: one prospective cohort (RAF-NOAC, 2017) and two randomized trials (TIMING, 2022; ELAN, 2023). Definitions of “early” ranged from ≤48 h (minor/moderate strokes) to ≤4 days; “delayed” ranged from day 5–10 or >14 days, with follow-up to 90 days (ELAN also reported 30- day outcomes). Across studies, early DOAC initiation was not associated with increased ICH; symptomatic ICH was rare (e.g., 0% in TIMING; ~0.2% in both ELAN arms). Efficacy signals favored early treatment: composite endpoints were numerically lower with early initiation in TIMING (6.9% vs 8.7%) and ELAN (2.9% vs 4.1%), with similar or lower major bleeding (e.g., 1.4% vs 2.5% in ELAN). Observational data (RAF-NOAC) suggested the most favorable outcomes when treatment began 3–14 days after stroke, with slightly higher events at ≤2 days. Subgroup analyses in RCTs showed no significant effect modification by age, sex, stroke severity, or reperfusion status. Conclusions: In AF-related ischemic stroke, early DOAC resumption appears safe and at least non-inferior to delayed strategies, with signals of reduced recurrent ischemia and no excess ICH. A tailored, severity-informed approach—especially leveraging imaging—seems appropriate, while very-early initiation (≤48 h) may warrant caution in large infarcts. These findings support guideline evolution toward earlier anticoagulation in suitable patients and underscore the need for longerterm outcomes and refined risk-stratification tools.
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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 | 0.020 | 0.030 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.067 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".