Evidence mapPaperPMID 42328643Full record

ArticleFrontiers in pharmacology2026

Real-world bleeding risk and molecular interaction profiles of direct oral anticoagulants: a comparative study integrating clinical outcomes and

Lutfi Cagatay Onar, Ersin Guner, Ibrahim Yilmaz

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Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Lutfi Cagatay OnarDepartment of Cardiovascular Surgery, Dr. Ismail Fehmi Cumalioglu City Hospital, Ministry of Health, Republic of Turkey, Tekirdag, Türkiye.
Ersin GunerDepartment of Pharmacy, Konya Numune Hospital, Ministry of Health, Republic of Turkey, Konya, Türkiye.
Ibrahim YilmazUnit of Pharmacovigilance, Dr. Ismail Fehmi Cumalioglu City Hospital, Ministry of Health, Republic of Turkey, Tekirdag, Türkiye.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Differences in bleeding risk among direct oral anticoagulants (DOACs) may reflect not only exposure-related factors but also molecule-specific drug-target interaction characteristics. This study aimed to evaluate real-world bleeding outcomes and to complement these findings with molecular docking analyses as supportive, hypothesis-generating mechanistic context for safety differences among factor Xa inhibitors and a direct thrombin inhibitor. Methods: A retrospective cohort of 5,721 patients treated with apixaban, rivaroxaban, edoxaban, or dabigatran was analyzed using real-world clinical data. Demographic characteristics, comorbidities, non-life-threatening complications, life-threatening hemorrhagic events, and overall bleeding outcomes were systematically compared. Multivariable logistic regression modeling was used to identify independent predictors of bleeding, with apixaban as the reference agent. Molecular docking analyses were performed using AutoDock 4.2.6 to assess comparative binding energy profiles, hydrogen bond interactions, and root-mean-square deviation values between each DOAC and factor Xa or thrombin. Results: Life-threatening bleeding occurred in 3.1% of patients, while any bleeding event was observed in 13.5% of the cohort. Compared with apixaban, rivaroxaban (OR 1.52), dabigatran (OR 1.29), and edoxaban (OR 1.44) were independently associated with higher odds of bleeding. Advanced age and renal dysfunction were identified as additional independent predictors. Docking analyses indicated that apixaban exhibited the lowest docking-derived binding energy toward factor Xa (ΔG = -14.46 kcal/mol), whereas dabigatran showed selective interaction with thrombin (ΔG = -11.91 kcal/mol). These molecular findings are exploratory and hypothesis-generating and should be interpreted as supportive mechanistic context rather than direct predictors of clinical outcomes. Conclusion: In this retrospective cohort, apixaban was associated with a comparatively lower observed bleeding risk compared with other DOAC agents. Docking findings provide exploratory, hypothesis-generating mechanistic context that may help to contextualize observed clinical patterns.

Indexed as

bleeding riskdirect oral anticoagulantsfactor Xa inhibitorsmolecular dockingprecision anticoagulationreal-world datathrombin inhibitor

Identifiers

PMID42328643
PMCPMC13279725

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.