Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis | Journal Scan

Study Questions:

What is the efficacy and safety profile of a factor XI antisense oligonucleotide (FXI-ASO) as compared to enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty?

Methods:

In an open-label, parallel-group study, 300 patients undergoing total knee arthroplasty were randomly assigned to one of two doses of FXI-ASO (200 mg or 300 mg) or enoxaparin 40 mg daily. Rates of VTE as well as major and clinically relevant nonmajor bleeding events were assessed for each group.

Results:

FXI-ASO reduced factor XI levels appropriately (0.38 ± 0.01 U/ml and 0.20 ± 0.01 U/ml vs. 0.93 ± 0.02 U/ml in the 200 mg FXI-ASO, 300 mg FXI-ASO, and enoxaparin groups, respectively). A VTE occurred in 27%, 4%, and 30% of patients in the 200 mg FXI-ASO, 300 mg FXI-ASO, and enoxaparin groups, respectively (p < 0.001 for 300 mg FXI-ASO vs. enoxaparin). Major and clinically relevant nonmajor bleeding occurred in 3%, 3%, and 8% of patients in the 200 mg FXI-ASO, 300 mg FXI-ASO, and enoxaparin groups, respectively. Injection-site-related adverse events occurred in 23, 25, and 2 patients in the FXI-ASO 200 mg, FXI-ASO 300 mg, and enoxaparin groups.

Conclusions:

The authors concluded that reducing factor XI levels using FXI-ASO is highly effective with no increased risk of bleeding as compared to enoxaparin for the prevention of VTE in patients undergoing total knee arthroplasty.

Perspective:

The authors provide exciting evidence of a potential new target to prevent VTE development in a high-risk surgical population. Perhaps most exciting is that the FXI-ASO at the 300 mg dose appeared to be superior for VTE prevention with similar bleeding risk compared to enoxaparin. While there are some concerns with a primary outcome that includes mandatory venogram for asymptomatic disease, the low risk of bleeding and the blinded adjudication of study outcomes are reassuring. Further studies will be needed to assess the severity of the injection-site-related adverse events with FXI-ASO. In the meantime, clinicians still need to balance the harms and benefits associated with various therapies intended to reduce VTE risk in orthopedic surgery patients.

Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Arthroplasty, Replacement, Knee, Asymptomatic Diseases, Enoxaparin, Factor XI, Hemorrhage, Orthopedic Procedures, Venous Thromboembolism, Venous Thrombosis


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