Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

LanAnh Ngo, PharmD Candidate 2015 Mercer University College of Pharmacy

Current antithrombotic therapies have significant impacts on patient outcomes. These therapies are important in many different types of settings, but is often associated with a risk of bleeding. An emerging new target of therapy, factor XI antisense oligonucleotide, functions to reduce the levels of factor XI, thereby reducing levels of thrombosis, but without the risk of bleeding.1

Title: Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis1
Design Open label, parallel group, randomized study
Objective The study compared the efficacy and safety of factor XI antisense oligonucleotide (FXI-ASO) with those of enoxaparin in patients undergoing total knee arthroplasty.
Study Groups Patients received one of two doses of FXI-ASO or enoxaparin.
Methods A total of 300 patients who were undergoing elective primary unilateral total knee arthroplasty were randomly assigned to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily.
Duration 136 days
Primary Outcome Measure The primary efficacy outcome measured was the incidence of adjudicated total venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events).
Baseline Characteristics The average age of patients were around 63 – 64 years in all groups.   The percentage of female were 82%, 78%, and 83% in the 200-mg FXI-ASO, 300-mg dose FXI-ASO, and enoxaparin study groups, respectively.  Duration of surgery, time to ambulation, and length of hospital stay were similar in all groups.
Results The primary efficacy outcome occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients (30%) who received enoxaparin.
Adverse Events Common Adverse Events: Bleeding occurred in 3%, 3%, and 8% of the patients in the 200-mg dose FXI-ASO, 300-mg dose FXI-ASO, and enoxaparin study groups, respectively.
Serious Adverse Events: 3% in 200-mg FXI-ASO group and 1% in 300-mg FXI-ASO group
Percentage that Discontinued due to Adverse Events: 1% in each FXI-ASO groups
Study Author Conclusions This study showed that factor XI contributes to postoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding.

While this study showed the use of FXI-ASO in patients undergoing unilateral total knee arthroplasty to be effective for the prevention of postoperative venous thromboembolism without the risk of bleeding, future studies should be conducted to examine FXI-ASO use in other types of surgeries or compared with other antiplatelet or anticoagulants.  Additionally, the safety profile of FXI-ASO should be looked at in more depth with regards to drug interactions, disease states, dose adjustments, and treatment reversal methods in an event of an overdose.

References:

  1. Buller H, Bethune C, Bhanot S, Gailani D, Monia B, Raskob G, et al. Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis. N Engl J Med 2015; 372:232-40.
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