Jan Steffel1, Robert P Giugliano2, Eugene Braunwald2, Sabina A Murphy2, Michele Mercuri3, Youngsook Choi3, Phil Aylward4, Harvey White5, Jose Luis Zamorano6, Elliott M Antman2, Christian T Ruff7. 1. Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland. 2. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. 3. Daiichi-Sankyo Pharma Development, Edison, New Jersey. 4. Flinders Medical Centre, Adelaide, Australia. 5. Auckland City Hospital, Auckland, New Zealand. 6. Ramón y Cajal University Hospital, Madrid, Spain. 7. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: cruff@partners.org.
Abstract
BACKGROUND: Anticoagulation is often avoided in patients with atrial fibrillation who are at an increased risk of falling. OBJECTIVES: This study assessed the relative efficacy and safety of edoxaban versus warfarin in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial in patients with atrial fibrillation judged to be at increased risk of falling. METHODS: We performed a pre-specified analysis of the ENGAGE AF-TIMI 48, comparing patients with versus without increased risk of falling. RESULTS: Nine hundred patients (4.3%) were judged to be at increased risk of falling. These patients were older (median, 77 vs. 72 years; p < 0.001), and had a higher prevalence of comorbidities including prior stroke/transient ischemic attack, diabetes, and coronary artery disease. After multivariable adjustment, patients at increased risk of falling experienced more bone fractures caused by falling (adjusted hazard ratio [HRadj]: 1.88; 95% confidence interval [CI]: 1.49 to 2.38; p < 0.001), major bleeding (HRadj: 1.30; 95% CI: 1.04 to 1.64; p = 0.023), life-threatening bleeding (HRadj: 1.67; 95% CI: 1.11 to 2.50; p = 0.013), and all-cause death (HRadj: 1.45; 95% CI: 1.23 to 1.70; p < 0.001), but not ischemic events including stroke/systemic embolic event (HRadj: 1.16; 95% CI: 0.89 to 1.51; p = 0.27). No treatment interaction was observed between either dosing regimens of edoxaban and warfarin for the efficacy and safety outcomes. Treatment with edoxaban resulted in a greater absolute risk reduction in severe bleeding events and all-cause mortality compared with warfarin. CONCLUSIONS:Edoxaban is an attractive alternative to warfarin in patients at increased risk of falling, because it is associated with an even greater absolute reduction in severe bleeding events and mortality. (Effective aNticaoGulation with factor xA next Generation in Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391).
RCT Entities:
BACKGROUND: Anticoagulation is often avoided in patients with atrial fibrillation who are at an increased risk of falling. OBJECTIVES: This study assessed the relative efficacy and safety of edoxaban versus warfarin in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial in patients with atrial fibrillation judged to be at increased risk of falling. METHODS: We performed a pre-specified analysis of the ENGAGE AF-TIMI 48, comparing patients with versus without increased risk of falling. RESULTS: Nine hundred patients (4.3%) were judged to be at increased risk of falling. These patients were older (median, 77 vs. 72 years; p < 0.001), and had a higher prevalence of comorbidities including prior stroke/transient ischemic attack, diabetes, and coronary artery disease. After multivariable adjustment, patients at increased risk of falling experienced more bone fractures caused by falling (adjusted hazard ratio [HRadj]: 1.88; 95% confidence interval [CI]: 1.49 to 2.38; p < 0.001), major bleeding (HRadj: 1.30; 95% CI: 1.04 to 1.64; p = 0.023), life-threatening bleeding (HRadj: 1.67; 95% CI: 1.11 to 2.50; p = 0.013), and all-cause death (HRadj: 1.45; 95% CI: 1.23 to 1.70; p < 0.001), but not ischemic events including stroke/systemic embolic event (HRadj: 1.16; 95% CI: 0.89 to 1.51; p = 0.27). No treatment interaction was observed between either dosing regimens of edoxaban and warfarin for the efficacy and safety outcomes. Treatment with edoxaban resulted in a greater absolute risk reduction in severe bleeding events and all-cause mortality compared with warfarin. CONCLUSIONS:Edoxaban is an attractive alternative to warfarin in patients at increased risk of falling, because it is associated with an even greater absolute reduction in severe bleeding events and mortality. (Effective aNticaoGulation with factor xA next Generation in Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391).
Authors: Thomas W Weiss; Miklos Rohla; Benjamin Dieplinger; Hans Domanovits; Dietmar Fries; Milan R Vosko; Thomas Gary; Cihan Ay Journal: Wien Med Wochenschr Date: 2017-02-24
Authors: Pamela L Lutsey; Faye L Norby; Kristine E Ensrud; Richard F MacLehose; Susan J Diem; Lin Y Chen; Alvaro Alonso Journal: JAMA Intern Med Date: 2020-02-01 Impact factor: 21.873