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J Am Heart Assoc. 2017 Jul 11;6(7). pii: e006015. doi: 10.1161/JAHA.117.006015.

Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy.

Author information

1
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA mgibson@bidmc.harvard.edu.
2
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
3
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
4
Division of Cardiology, R.A.H Faculty of Medicine, University of Calgary, Alberta, Canada.
5
Duke University and Duke Clinical Research Institute, Durham, NC.
6
Portola Pharmaceuticals Inc., South San Francisco, CA.
7
Guy's and St Thomas' Hospitals, London, United Kingdom.
8
Department of Medicine, Stanford University, Stanford, CA.

Abstract

BACKGROUND:

Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm.

METHODS AND RESULTS:

This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]).

CONCLUSIONS:

Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin.

CLINICAL TRIAL REGISTRATION:

URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.

KEYWORDS:

death; intracranial hemorrhage; ischemic stroke; myocardial infarction; pulmonary embolism; venous thromboembolism

PMID:
28698258
PMCID:
PMC5586307
DOI:
10.1161/JAHA.117.006015
[Indexed for MEDLINE]
Free PMC Article

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