TY - JOUR
T1 - Extended thromboprophylaxis with betrixaban in acutely ill medical patients
AU - APEX Investigators
AU - Cohen, Alexander T.
AU - Harrington, Robert A.
AU - Goldhaber, Samuel Z.
AU - Hull, Russell D.
AU - Wiens, Brian L.
AU - Gold, Alex
AU - Hernandez, Adrian F.
AU - Gibson, C. Michael
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 - Colquhoun, D.
AU - Coughlin, P.
AU - Finfer, S.
AU - Rubinfeld, A.
AU - Huber, K.
AU - König, J.
AU - Mathies, R.
AU - Pilger, E.
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 - Motte, S.
AU - Bizzacchi, J.
AU - Fiss, E.
AU - Freire, A.
AU - Manenti, E.
AU - Ramacciotti, E.
AU - Raymuno, S.
AU - Rocha, A.
AU - Saraiva, J. F.
AU - Dimov, B.
AU - Grigorov, M.
AU - Kalpachki, R.
AU - Kamenova, Z.
AU - Lugassy, G.
N1 - Publisher Copyright:
Copyright © 2016 Massachusetts Medical Society.
PY - 2016/8/11
Y1 - 2016/8/11
N2 - BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated D-dimer level (cohort 1), patients with an elevated D-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P = 0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P = 0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P = 0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P = 0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated D-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts.
AB - BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated D-dimer level (cohort 1), patients with an elevated D-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P = 0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P = 0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P = 0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P = 0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated D-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts.
UR - http://www.scopus.com/inward/record.url?scp=84981709094&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1601747
DO - 10.1056/NEJMoa1601747
M3 - Article
C2 - 27232649
AN - SCOPUS:84981709094
SN - 0028-4793
VL - 375
SP - 534
EP - 544
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -