Format

Send to:

Choose Destination
See comment in PubMed Commons below
N Engl J Med. 2015 Jan 15;372(3):232-40. doi: 10.1056/NEJMoa1405760. Epub 2014 Dec 7.

Factor XI antisense oligonucleotide for prevention of venous thrombosis.

Author information

  • 1From the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.), and International Trial Expertise Advisory and Services (ITREAS) (A.S.) - both in Amsterdam; Isis Pharmaceuticals, Carlsbad, CA (C.B., S.B., B.P.M.); Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville (D.G.); University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City (G.E.R.); KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); and the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON, Canada (J.I.W.).

Abstract

BACKGROUND:

Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty.

METHODS:

In this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events). The principal safety outcome was major or clinically relevant nonmajor bleeding.

RESULTS:

Around the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group, and 0.93±0.02 units per milliliter in the enoxaparin group. 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. The 200-mg regimen was noninferior, and the 300-mg regimen was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in the three study groups, respectively.

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. (Funded by Isis Pharmaceuticals; FXI-ASO TKA ClinicalTrials.gov number, NCT01713361.).

PMID:
25482425
[PubMed - indexed for MEDLINE]
PMCID:
PMC4367537
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Write to the Help Desk