Direct oral anticoagulants and Factor XI inhibition: Advances and future directions in anticoagulant therapy

Anticoagulant therapy remains central to the prevention and treatment of thromboembolic disease, including atrial fibrillation, venous thromboembolism, and a broad range of other cardiovascular conditions. Over the past decade, direct oral anticoagulants (DOACs) have transformed practice by offering effective alternatives to vitamin K antagonists, with more predictable pharmacokinetics, fewer dietary interactions, and simplified dosing. Nevertheless, important clinical challenges persist, including bleeding risk, interindividual variability in response, renal and hepatic impairment, peri-procedural management, drug-drug interactions, and use in complex populations. In parallel, factor XI and factor XIa inhibition has emerged as one of the most promising new directions in anticoagulant development. By selectively targeting pathways more closely linked to pathological thrombosis than to physiological haemostasis, these agents may open the way to safer antithrombotic strategies.This Research Topic aims to provide a forward-looking and clinically relevant overview of current advances in anticoagulant pharmacology, with particular emphasis on direct oral anticoagulants and novel factor XI inhibitors. Although DOACs are now well established in daily practice, many unresolved issues remain regarding optimal drug selection, bleeding mitigation, management in high-risk settings, treatment individualization, and translation of evidence into real-world care. At the same time, factor XI inhibition may represent a major conceptual shift in antithrombotic therapy by improving the balance between thrombosis prevention and bleeding risk. This collection seeks to bring together basic, translational, clinical, and real-world contributions that clarify mechanisms, compare therapeutic strategies, examine special populations, and define future research priorities. The overarching objective is to create a rigorous and useful forum that connects pharmacology with practice and highlights where the next generation of anticoagulant therapy is heading.We welcome submissions addressing the pharmacokinetics and pharmacodynamics of DOACs and factor XI / XIa inhibitors; comparative efficacy and safety; bleeding mechanisms and reversal strategies; laboratory assessment and monitoring; drug-drug interactions; perioperative and peri-procedural management; and use in atrial fibrillation, venous thromboembolism, cancer-associated thrombosis, renal impairment, hepatic disease, older adults, and other complex populations. We also encourage manuscripts focused on mechanistic and preclinical work, biomarker-guided therapy, implementation science, real-world evidence, and precision approaches to anticoagulant selection. Manuscript types of interest include Original Research, Review, Systematic Review, Mini Review, Brief Research Report, Clinical Trial, Methods, and Perspective articles.We invite researchers, clinicians, translational scientists, and pharmacology experts to contribute cutting-edge work to this Research Topic on modern anticoagulant therapy. This collection aims to capture both the mature clinical impact of direct oral anticoagulants and the rapidly expanding therapeutic promise of factor XI inhibition. Submissions that bridge mechanisms with clinical decision-making, address unmet needs in bleeding reduction, or propose future directions for safer and more individualized antithrombotic care will be especially welcome. By combining trial data, pharmacological insights, implementation research, and real-world evidence, this Research Topic seeks to stimulate a high-level discussion that is scientifically rigorous, clinically useful, and genuinely field-shaping. Topic editors: Alina Scridon, JUAN-CARLOS KASKI, Vasile Bogdan Halatiu, Antoni Martinez-Rubio Source: https://www.frontiersin.org/research-topics/80011/direct-oral-anticoagulants-and-factor-xi-inhibition-advances-and-future-directions-in-anticoagulant-therapy