Abstract 19208: Extended Duration Betrixaban Reduces the Risk of Stroke vs Standard Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Substudy
Introduction: Among patients hospitalized for medical conditions, stroke may be a major complication, including intracranial hemorrhage (ICH). In the APEX trial, we examined the potential to reduce the risk of stroke with extended duration betrixaban, a factor Xa inhibitor with a long half-life (19-25 hours) and low renal clearance (5% of administered dose) as compared to standard dose enoxaparin among medically ill patients.
Methods: Hospitalized medically ill subjects (n=7,513) were randomized in a double dummy double blind fashion to either extended-duration oral betrixaban (35 days) or standard-duration subcutaneous enoxaparin (10 ± 4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent committee and were assessed through last patient contact.
Results: There were fewer total strokes among those patients treated with betrixaban, (0.6%; 24/3716) vs enoxaparin, (1.1%; 41/3716, HR = 0.58 (0.35-0.97), p=0.034) and fewer ischemic strokes with betrixaban 0.5% (18/3716) vs enoxaparin (0.9%; 34/3716, HR = 0.53 (0.30-0.94), p=0.026). Among the highest risk patients with a history of ischemic stroke or congestive heart failure as the index event, betrixaban reduced all stroke, (HR = 0.55 (0.31, 0.97), p=0.038) and ischemic stroke, (HR = 0.45 (0.24, 0.87), p=0.014). There were numerically but not significantly fewer ICHs in the betrixaban group: 0.05% (2/3716) vs 0.19% (7/3716), p=0.18.
Conclusions: Among hospitalized medically ill patients, extended duration betrixaban significantly reduced all stroke by 42% and ischemic stroke by 47% as compared to standard dose enoxaparin while also yielding a numerically lower number of ICHs vs. standard dose enoxaparin.
Author Disclosures: C. Gibson: Research Grant; Significant; Angel Medical Corporation, Bayer Corp., CSL Behring, Ikaria, Inc., Janssen Pharmaceuticals, Johnson & Johnson Corporation, Portola Pharmaceuticals, Stealth Peptides, Inc., St. Jude Medical. Other Research Support; Modest; The Medicines Company. Consultant/Advisory Board; Modest; Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences, Inc., The Medicines Company, Novo Nordisk, Pfizer, St. Jude Medical, Web MD. Y. Daaboul: None. S. Korjian: None. D. Szolsek: None. P. Jain: None. G. Chi: None. A. Hernandez: Other Research Support; Modest; Amgen, AstraZeneca, Bayer, Merck, Novartis, Bristol Myers Squib, Portola Pharmaceuticals. Honoraria; Modest; AstraZeneca, Bayer, Novartis. R. Hull: Research Grant; Modest; Portola Pharmaceuticals, Leo Pharma. S. Goldhaber: Research Grant; Modest; BiO2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, BTG EKOS, Daiichi-Sankyo, National Heart Lung and Blood Institute of the National Institutes of Health, Janssen, Thrombosis Research Group. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, Bayer, Portola Pharmaceuticals. R.A. Harrington: Research Grant; Modest; Portola Pharmaceuticals, CSL Behring, AstraZeneca, GlaxoSmithKline, Merck, Regado, The Medicines Company, Sanofi Aventis. Consultant/Advisory Board; Modest; Merck, The Medicines Company, Amgen, Gilead Sciences, MyoKardia, WebMD. Other; Modest; Scanadu, SignalPath, Element Science, Vida Health, Adverse Events. B.L. Wiens: Employment; Significant; Portola Pharmaceuticals. A. Gold: Employment; Significant; Portola Pharmaceuticals. A.T. Cohen: Research Grant; Modest; Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer. Honoraria; Modest; Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, Johnson and Johnson, Janssen, Bayer HealthCare. Consultant/Advisory Board; Modest; Portola Pharmaceuticals, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Johnson and Johnson, Sanofi Aventis, XO1, Janssen, Bayer HealthCare.
- © 2016 by American Heart Association, Inc.