Prajapathi Sudesh, Pradhan Akshyaya, Mohta Aditi, Sethi Rishi
Department of Cardiology, King George's Medical University, Shahmina Road, Chowk, Lucknow, Uttar Pradesh, 226003, India.
Department of Community Medicine, Integral Institute of Medical Sciences and Research, Lucknow, Uttar Pradesh, India.
Egypt Heart J. 2024 Oct 10;76(1):137. doi: 10.1186/s43044-024-00570-7.
Arterial or venous thromboembolic events are responsible for one-fourth of all deaths worldwide. Anticoagulants are the mainstay for the prevention and treatment of venous thromboembolic events (VTE). Heparin and vitamin K antagonists were the first non-specific medications used in anticoagulant therapy, followed by safer alternatives, such as fondaparinux, argatroban, and direct oral anticoagulants. However, the latter bear the risk of potentially lethal internal bleeding. Novel drugs inhibiting various coagulation factors, such as factors XIa, XIIa, and XIIIa, appear to have a lesser risk of bleeding and are in the spotlight. This review aims to consolidate findings from published clinical trials of newer drugs inhibiting factors XIa, XIIa, and XIIIa.
Factor XI inhibitors have been researched more extensively as compared to factor XII and factor XIII inhibitors. Phase 2 study results of factor XI inhibitors indicated their superiority over enoxaparin for reduction of VTE incidence and better safety profile in terms of bleeding. Factor XII inhibitors also hold the promise of lowering the risk of bleeding, as indicated in animal studies. Further human studies would ensure their safety and applicability in the human population. Numerous laboratory researches have revealed, the potent antithrombotic profile of factor XIII inhibition with limited bleeding risks.
Larger statistically powered studies could supplement data to establish the role of FXI inhibitors in the prevention of both arterial and venous thromboembolic events in high-risk populations. While early results of factor XII and factor XIII inhibitors look promising, they still have a long road ahead before their therapeutic efficacy in humans is established.
动脉或静脉血栓栓塞事件导致全球四分之一的死亡。抗凝剂是预防和治疗静脉血栓栓塞事件（VTE）的主要手段。肝素和维生素K拮抗剂是抗凝治疗中最早使用的非特异性药物，随后出现了更安全的替代品，如磺达肝癸钠、阿加曲班和直接口服抗凝剂。然而，后者存在潜在致命性内出血的风险。抑制各种凝血因子（如因子XIa、XIIa和XIIIa）的新型药物似乎出血风险较小，备受关注。本综述旨在汇总已发表的关于抑制因子XIa、XIIa和XIIIa的新型药物临床试验结果。
与因子XII和因子XIII抑制剂相比，因子XI抑制剂的研究更为广泛。因子XI抑制剂的2期研究结果表明，在降低VTE发生率方面，它们优于依诺肝素，并且在出血方面具有更好的安全性。动物研究表明，因子XII抑制剂也有望降低出血风险。进一步的人体研究将确保其在人群中的安全性和适用性。大量实验室研究表明，抑制因子XIII具有强大的抗血栓作用，且出血风险有限。
更大规模、具有统计学效力的研究可以补充数据，以确定FXI抑制剂在高危人群预防动脉和静脉血栓栓塞事件中的作用。虽然因子XII和因子XIII抑制剂的早期结果看起来很有前景，但在确定它们在人体中的治疗效果之前，仍有很长的路要走。
