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Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.

Publication ,  Journal Article
Cohen, AT; Harrington, RA; Goldhaber, SZ; Hull, RD; Wiens, BL; Gold, A; Hernandez, AF; Gibson, CM; APEX Investigators,
Published in: N Engl J Med
August 11, 2016

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. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

August 11, 2016

Volume

375

Issue

6

Start / End Page

534 / 544

Location

United States

Related Subject Headings

  • Venous Thrombosis
  • Venous Thromboembolism
  • Ultrasonography
  • Risk Factors
  • Pyridines
  • Pulmonary Embolism
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
 

Citation

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Cohen, A. T., Harrington, R. A., Goldhaber, S. Z., Hull, R. D., Wiens, B. L., Gold, A., … APEX Investigators, . (2016). Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med, 375(6), 534–544. https://doi.org/10.1056/NEJMoa1601747
Cohen, Alexander T., Robert A. Harrington, Samuel Z. Goldhaber, Russell D. Hull, Brian L. Wiens, Alex Gold, Adrian F. Hernandez, C Michael Gibson, and C Michael APEX Investigators. “Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.N Engl J Med 375, no. 6 (August 11, 2016): 534–44. https://doi.org/10.1056/NEJMoa1601747.
Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016 Aug 11;375(6):534–44.
Cohen, Alexander T., et al. “Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.N Engl J Med, vol. 375, no. 6, Aug. 2016, pp. 534–44. Pubmed, doi:10.1056/NEJMoa1601747.
Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM, APEX Investigators. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016 Aug 11;375(6):534–544.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

August 11, 2016

Volume

375

Issue

6

Start / End Page

534 / 544

Location

United States

Related Subject Headings

  • Venous Thrombosis
  • Venous Thromboembolism
  • Ultrasonography
  • Risk Factors
  • Pyridines
  • Pulmonary Embolism
  • Middle Aged
  • Male
  • Humans
  • Hospitalization