TY - JOUR
T1 - Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis
AU - Büller, Harry R.
AU - Bethune, Claudette
AU - Bhanot, Sanjay
AU - Gailani, David
AU - Monia, Brett P.
AU - Raskob, Gary E.
AU - Segers, Annelise
AU - Verhamme, Peter
AU - Weitz, Jeffrey I.
AU - AUTHOR GROUP
AU - Weitz, Jeffrey
AU - Prins, Martin
AU - Beenen, Ludo
AU - Otten, Hans-Martin
AU - Roos, Yvo
AU - Slagboom, Ton
AU - Vandenbriele, Christophe
AU - Vanassche, Thomas
AU - Dani, Vidhi
AU - Schulz, Dan
AU - Shapiro, Cara
AU - Kwoh, Katherine
AU - Jung, Bill
AU - Gawinek-Samelczak, Agata
AU - Kaemmer, Christina
AU - Angelov, S.
AU - Stavrev, V.
AU - Kinov, P.
AU - Dessouki, E.
AU - Abuzgaya, F.
AU - Baurovskis, A.
AU - Peredistijs, A.
AU - Petronis, S.
AU - Danilyak, V.
AU - Driagin, V.
AU - Kuropatkin, G.
AU - Parfeev, S.
AU - Safronov, A.
AU - Ankin, M.
AU - Korzh, M.
AU - Olinichenko, G.
AU - Polivoda, A.
AU - Shevchenko, V.
AU - Sulyma, V.
PY - 2015
Y1 - 2015
N2 - 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. Copyright (C) 2014 Massachusetts Medical Society
AB - 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. Copyright (C) 2014 Massachusetts Medical Society
U2 - https://doi.org/10.1056/NEJMoa1405760
DO - https://doi.org/10.1056/NEJMoa1405760
M3 - Article
C2 - 25482425
SN - 0028-4793
VL - 372
SP - 232
EP - 240
JO - New England journal of medicine
JF - New England journal of medicine
IS - 3
ER -