Factor XIa Inhibitors as a Novel Anticoagulation Target: Recent Clinical Research Advances

Abstract

Background: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. Objective: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. Results: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606–1.046; I2 = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502–1.023; I2 = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256–0.816; I2 = 0%). Conclusions: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors

“…Potential strategies could involve targeting other enzymes in-volved in the coagulation cascade, such as thrombin or Factor VIIa, or developing novel approaches to modulate platelet activation and aggregation. Additionally, advances in understanding the signaling pathways and interactions involving HGF could offer new insights for therapeutic interventions in the blood clotting system [68,69]. Also, further research is needed to explore alternative drug targets and develop safer and more effective anticoagulant therapies, ensuring a balance between preventing thrombosis and minimizing the risk of bleeding complications.…”

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose‐escalation phase I study

“… 10 , 11 Clinical trials of FXIa inhibitors have furnished encouraging results in preventing venous thromboembolism. 12 A recent review 13 summarized that 33 trials have been conducted to assess the efficacy/safety of FXIa inhibitors in various indications. FXIa inhibitors developed mainly include ASO (ISIS 416858, 14 IONIS‐FXIRX 15 ), antibodies (MAA868, 16 , 17 BAY‐1213790, 18 , 19 and AB023 20 , 21 ), and small molecule drugs (frunexian, 22 BMS‐962212, 23 BAY‐2433334 24 ).…”

Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis

“…Evidence from in vivo animal models [10,11], patients with inherited factor XI deficiency [12], and randomized controlled clinical trials (RCTs) using antisense oligonucleotides [13], monoclonal antibodies [14,15], and small molecules targeting factor XIa [16] suggest that factor XIa inhibition may offer a safer anticoagulant option compared with previous generations of anticoagulants. Recently, a systematic review and meta-analysis summarizing the results of available RCTs comparing patients receiving factor XIa inhibitors versus controls did not detect any difference in hemorrhagic events between the two groups and confirmed the favorable safety profile of factor XIa inhibitors [17]. However, this study was limited by the inclusion of a quite heterogenous patient population (by merging patients at high risk for cardio-and cerebrovascular events [5][6][7] with those undergoing knee arthroplasty and requiring venous thromboembolism prevention [13][14][15][16]) and by the fact that it did not specifically assess stroke occurrence as an outcome of interest.…”