Cardiovascular- and Bleeding-Related Hospitalization Rates With Edoxaban Versus Warfarin in Patients With Atrial Fibrillation Based on Results of the ENGAGE AF-TIMI 48 Trial.

Abstract

Background The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations. Methods Detailed healthcare resource utilization data from ENGAGE AF-TIMI 48 for the 14 024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms. Results The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85-0.97], P=0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85-0.97], P=0.004), stroke (RR, 0.80 [95% CI, 0.72-0.88], P<0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81-0.99], P=0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54-0.68], P<0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke-related hospitalizations in vitamin K antagonist naive patients and patients with CHADS2 scores 4 to 6, previous stroke or transient ischemic attack, age ≥75, and no previous coronary artery disease. For nonstroke bleeding-related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS2 scores 4 to 6, and patients with moderate renal dysfunction. Conclusions Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular-related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.

• Authors: Katherine Vilain, Haiyan Li, Wingham J Kwong, Elliott M Antman, Christian T Ruff, Eugene Braunwald, David J Cohen, Robert P Giugliano, Elizabeth A Magnuson, ENGAGE AF-TIMI 48 Trial Investigators
• Journal: Circulation. Cardiovascular quality and outcomes (Circ Cardiovasc Qual Outcomes) Vol. 13 Issue 11 Pg. e006511 (11 2020) ISSN: 1941-7705 [Electronic] United States
• PMID: 33148013 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Pyridines
• Thiazoles
• Warfarin
• edoxaban

Topics

• Aged
• Anticoagulants (adverse effects)
• Atrial Fibrillation (diagnosis, drug therapy, epidemiology)
• Cardiovascular Diseases (diagnosis, epidemiology, prevention & control)
• Factor Xa Inhibitors (adverse effects)
• Female
• Hemorrhage (chemically induced, epidemiology, prevention & control)
• Hospitalization
• Humans
• Male
• Middle Aged
• Pyridines (adverse effects)
• Risk Assessment
• Risk Factors
• Thiazoles (adverse effects)
• Time Factors
• Treatment Outcome
• Warfarin (adverse effects)