TY - JOUR
T1 - The safety and efficacy of full-versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial
AU - APEX Investigators
AU - Gibson, C. Michael
AU - Halaby, Rim
AU - Korjian, Serge
AU - Daaboul, Yazan
AU - Arbetter, Douglas F.
AU - Yee, Megan K.
AU - Goldhaber, Samuel Z.
AU - Hull, Russel
AU - Hernandez, Adrian F.
AU - Lu, Shiao-ping
AU - Bandman, Olga
AU - Leeds, Janet M.
AU - Gold, Alex
AU - Harrington, Robert A.
AU - Cohen, Alexander T.
AU - Bello, F.
AU - Ferrari, A. E.
AU - Jure, H.
AU - Macin, S.
AU - Oliva, M.
AU - Parody, M.
AU - Poy, C.
AU - Baker, R.
AU - Coughlin, P.
AU - Finfer, S.
AU - Rubinfeld, A.
AU - Huber, K.
AU - Konig, J.
AU - Mathies, R.
AU - Schoenerr, H.
AU - Adzerikho, I.
AU - Koryk, V.
AU - Mikhailova, E.
AU - Mitkovskaya, N.
AU - Pimanov, S.
AU - Polonetsy, L.
AU - Soroka, N.
AU - Blockmans, D.
AU - Delforge, M.
AU - Dive, A.
AU - Lienart, F.
AU - Bizzacchi, J. Annichino
AU - Fiss, E.
AU - Freire, A.
AU - Manenti, E.
AU - Ramacciotti, E.
AU - Raymuno, S.
AU - Rocha, A.
AU - Dimov, B.
A2 - Stukena, I.
N1 - A list of APEX Investigators of this article is given in Web of Science database.
PY - 2017/3
Y1 - 2017/3
N2 - Background The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor. Methods This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. Results The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P < .001). In the primary analysis cohort 1 (D-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism–related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction = 0.26 [0.04-0.42], P = .023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction = 0.30 [0.13-0.44], P = .001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin. Conclusions The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.
AB - Background The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor. Methods This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. Results The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P < .001). In the primary analysis cohort 1 (D-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism–related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction = 0.26 [0.04-0.42], P = .023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction = 0.30 [0.13-0.44], P = .001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin. Conclusions The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.
U2 - 10.1016/j.ahj.2016.12.004
DO - 10.1016/j.ahj.2016.12.004
M3 - Article
SN - 0002-8703
VL - 185
SP - 93
EP - 100
JO - American Heart Journal
JF - American Heart Journal
ER -