Abstract 17392: Gastrointestinal Bleeding With Edoxaban versus Warfarin: Results From the ENGAGE AF-TIMI 48 Trial
Background: There is more major gastrointestinal bleeding (M-GIB) with most NOACs than with warfarin. The clinical impact of this finding is poorly understood.
Methods: The ENGAGE AF-TIMI 48 trial compared the efficacy and safety of higher-dose (HD-E: 60 mg/ 30mg) or lower-dose (LD-E: 30 mg/15 mg) edoxaban regimens with dose-adjusted warfarin for prevention of stroke and systemic embolism in non-valvular atrial fibrillation. ISTH definitions for major and life-threatening (LT) bleeding events were utilized. In this pre-specified analysis, we investigated the adjudicated M-GIB events utilizing pre-defined severity and outcome endpoints.
Results: Although the risk of M-GIB was higher with HD-E than with warfarin, the risk of LT or fatal GIB was similar (figure), and surgery for GIB was required less frequently with HD-E than warfarin (HR 0.37; 95%CI, 0.16-0.88; p=0.03). The risk for M-GIB-related permanent drug discontinuation was similar with HD-E and warfarin (HR 0.96; 95% CI, 0.67-1.37, p=0.8), as were the risks of hospitalization (HR 1.14; 95%CI, 0.92-1.40, p=0.2) and Hgb decrease > 5 g/dL (HR 1.01; 95%CI, 0.74-1.38; p=0.9). The risks of M-GIB and of LT or fatal GIB were lower with LD-E than with warfarin (Figure), as were the risks of M-GIB-related permanent drug discontinuation (HR 0.51; 95% CI, 0.33-0.78, p=0.002), hospitalization (HR 0.67; 95%CI, 0.53-0.85; p=0.001), Hgb decrease > 5 g/dL (HR 0.58; 95%CI, 0.40-0.84; p=0.003), and M-GIB requiring transfusion of > 2 units of red cells (HR 0.66; 95%CI, 0.50-0.89; p=0.006). Fatal GIB occurred in 2, 3 and 7 patients treated with HD-E, LD-E and warfarin, respectively.
Conclusions: M-GIB and LT-GIB with edoxaban are dose-dependent. Although the risk of M-GIB is higher with HD-E than warfarin, the risk of LT-GIB or fatal GIB is similar and the severity and outcomes are no worse than with warfarin. The risks of M-GIB, and of LT-GIB or fatal GIB, are lower with LD-E than warfarin.
Author Disclosures: J. Aisenberg: Consultant/Advisory Board; Modest; Portola Pharmaceuticals. Consultant/Advisory Board; Significant; Boehringer Ingelheim. K. Friedman: None. J. Desai: Consultant/Advisory Board; Modest; Daiichi Sankyo. J.I. Weitz: Consultant/Advisory Board; Significant; Daiichi Sankyo, Boehringer Ingelheim, Bayer, Pfizer, BMS, Portola, Isis Pharmaceuticals, Johnson & Johnson. R. Giugliano: Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Amgen, GlaxoSmithKline, Merck, Portola, American College of Cardiology, CVS Caremark. Other; Modest; St Jude Medical. Research Grant; Significant; Amgen, Merck. Other; Significant; Lexicon. C.T. Ruff: Research Grant; Modest; Astra Zeneca, Eisai, Intarcia. Research Grant; Significant; Daiichi-Sankyo. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Bayer, Portola. Consultant/Advisory Board; Significant; Daiichi Sankyo. F. Nordio: None. M. Mercuri: Employment; Significant; Daiichi Sankyo. Y. Choi: Employment; Significant; Daiichi Sankyo. L. Bower: Employment; Significant; Daiichi Sankyo. E. Antman: Other; Modest; Daiichi Sankyo sponsored trial. E. Braunwald: Other; Modest; Daiichi Sankyo sponsored trial.
- © 2015 by American Heart Association, Inc.