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EDOXABAN VERSUS WARFARIN IN 841 PATIENTS WITH ATRIAL FIBRILLATION AND PERIPHERAL ARTERIAL DISEASE: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL
2262 JACC April 5, 2016 Volume 67, Issue 13
Vascular Medicine EDOXABAN VERSUS WARFARIN IN 841 PATIENTS WITH ATRIAL FIBRILLATION AND PERIPHERAL ARTERIAL DISEASE: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL Moderated Poster Contributions Vascular Medicine Moderated Poster Theater, Poster Area, South Hall A1 Monday, April 04, 2016, 12:45 p.m.-12:55 p.m. Session Title: Managing Risk in Patients With Peripheral Artery Disease: Insights From Trials, Registries, and Databases Abstract Category: 44. Vascular Medicine: Non Coronary Arterial Disease Presentation Number: 1289M-03 Authors: Jonathan Cunningham, Robert Giugliano, Eugene Braunwald, Marco Trevisan, Francesco Nordio, Ton Oude Ophuis, Mijo Bergovec, Michele Mercuri, Christian Ruff, Marc Bonaca, Brigham and Women’s Hospital, Boston, MA, USA
Background: Peripheral arterial disease (PAD) is associated with ischemic and bleeding risk. The balance of efficacy and safety of various antithrombotics in pts with atrial fibrillation (AF) and PAD is unclear. We compared edoxaban and warfarin in pts with AF and PAD. Methods: ENGAGE AF-TIMI 48 randomized 21,105 pts with AF to warfarin adjusted to an INR 2.0-3.0 (median TTR 68.4%), edoxaban 60/30mg (HDE) or 30/15mg (LDE). PAD (yes/no) was reported at baseline. The 1° efficacy and safety endpoints were stroke/systemic embolism (SE) and ISTH major bleeding respectively.
Results: Pts with PAD (841, 4%) had higher rates of SE, CV death and major bleeding than those without PAD (left figure). After adjustment, pts with PAD had significantly greater risk of SE and CV death; absolute risk of CV death was 2.3%/year greater in pts with PAD. Differences in CV death were driven by excess sudden death (Adj HR 1.63, p=0.002). In pts with PAD, rates of stroke/SE and major bleeding were similar with HDE and warfarin; no significant PAD subgroup treatment interactions were present across a variety of endpoints (right figure). LDE had higher rates of stroke/SE relative to warfarin (p-interaction 0.04).
Conclusions: In AF, concomitant PAD is associated with greater risk of SE and CV death. In pts with PAD, HDE had similar efficacy and safety relative to warfarin, while the significant reductions in CV death and intracranial hemorrhage with HDE seen in the main trial were preserved regardless of the presence or absence of PAD.
Vascular Medicine EDOXABAN VERSUS WARFARIN IN 841 PATIENTS WITH ATRIAL FIBRILLATION AND PERIPHERAL ARTERIAL DISEASE: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL Moderated Poster Contributions Vascular Medicine Moderated Poster Theater, Poster Area, South Hall A1 Monday, April 04, 2016, 12:45 p.m.-12:55 p.m. Session Title: Managing Risk in Patients With Peripheral Artery Disease: Insights From Trials, Registries, and Databases Abstract Category: 44. Vascular Medicine: Non Coronary Arterial Disease Presentation Number: 1289M-03 Authors: Jonathan Cunningham, Robert Giugliano, Eugene Braunwald, Marco Trevisan, Francesco Nordio, Ton Oude Ophuis, Mijo Bergovec, Michele Mercuri, Christian Ruff, Marc Bonaca, Brigham and Women’s Hospital, Boston, MA, USA
Background: Peripheral arterial disease (PAD) is associated with ischemic and bleeding risk. The balance of efficacy and safety of various antithrombotics in pts with atrial fibrillation (AF) and PAD is unclear. We compared edoxaban and warfarin in pts with AF and PAD. Methods: ENGAGE AF-TIMI 48 randomized 21,105 pts with AF to warfarin adjusted to an INR 2.0-3.0 (median TTR 68.4%), edoxaban 60/30mg (HDE) or 30/15mg (LDE). PAD (yes/no) was reported at baseline. The 1° efficacy and safety endpoints were stroke/systemic embolism (SE) and ISTH major bleeding respectively.
Results: Pts with PAD (841, 4%) had higher rates of SE, CV death and major bleeding than those without PAD (left figure). After adjustment, pts with PAD had significantly greater risk of SE and CV death; absolute risk of CV death was 2.3%/year greater in pts with PAD. Differences in CV death were driven by excess sudden death (Adj HR 1.63, p=0.002). In pts with PAD, rates of stroke/SE and major bleeding were similar with HDE and warfarin; no significant PAD subgroup treatment interactions were present across a variety of endpoints (right figure). LDE had higher rates of stroke/SE relative to warfarin (p-interaction 0.04).
Conclusions: In AF, concomitant PAD is associated with greater risk of SE and CV death. In pts with PAD, HDE had similar efficacy and safety relative to warfarin, while the significant reductions in CV death and intracranial hemorrhage with HDE seen in the main trial were preserved regardless of the presence or absence of PAD.