A303 SAFETY AND EFFICACY OF DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH LIVER CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Abstract Background Direct oral anticoagulants (DOACs) are widely used for treatment of venous thromboembolism (VTE) and stroke prophylaxis in patients with atrial fibrillation. Liver cirrhosis increases the risk of conditions necessitating anticoagulation, but also increases bleeding risks, complicating anticoagulation use. DOACs may be suitable for chirrotic patients as their reliance on hepatic elimination is reduced compared to traditionally used anticoagulants such as low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs). However, safety data on DOACs in cirrhosis patients is limited as severe Child-Pugh (CP) classes are historically underrepresented in major trials. Various guidelines currently classify severe CP classes as contraindications to DOACs. Aims To synthesize primary evidence on the safety profile of DOACs in patients with severe liver cirrhosis. Methods A literature search of MEDLINE and Embase from inception to Jan 2023 identified randomized controlled trials (RCTs) and cohort studies comparing DOACs to LMWH or VKAs in cirrhosis patients. Two reviewers screened and extracted data at title/abstract, and full-text levels. Baseline patient characteristics, CP class, and anticoagulation regimens were extracted. The primary outcome was major bleeding per ISTH criteria, stratified by CP B&C, and CP Unspecified (primary study did not report/stratify by CP class) subgroups. Data were meta-analyzed using the Mantel-Haenszel random-effects model and presented as odds ratios with corresponding 95% confidence intervals. Results Of 794 articles screened, 17 articles (2 RCTs, 15 cohorts) were included for analysis (n = 5046). Overall, DOACs were associated with a lower risk of major bleeding compared to controls (OR=0.63 [0.45, 0.89]). This result was consistent in the CP B&C Exclusive subgroup (OR=0.42 [0.29, 0.62], 5 studies) but not in the CP Unspecified subgroup (OR=0.71 [0.48, 1.08], 12 studies). One large study (n=3213), Lawal 2023, in the CP B&C group, favored DOACs in reduction of major bleeding (OR=0.37, 95%CI [0.24,0.57]). Removal of this study in post-hoc sensitivity analysis led to no significant differences in major bleeding overall or in any subgroup. Conclusions In this analysis comparing DOACs to LMWH/VKAs in patients with liver cirrhosis, DOACs were associated with a statistically significant reduction in the risk of major bleeding overall and in more advanced subgroups (CP B&C). Future analysis will stratify by DOAC agent, duration, dosage, and include secondary efficacy outcomes. Table 1. Summary of the major bleeding effect size in all subgroups. Figure 1. Major bleeding in Child-Pugh B&C and Child-Pugh Unspecified groups with DOAC vs VKA Funding Agencies None
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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 | 0.010 | 0.027 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.033 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".