BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

From Brigham and Women's Hospital and Harvard Medical School Boston

Komentář v

Nat Rev Cardiol. 2014 Feb;11(2):66. doi: 10.1038/nrcardio.2013.206. PubMed

Citace poskytuje Crossref.org

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia - One-Year Data From the Global ETNA-AF Program

Heterogeneity of outcomes within diabetic patients with atrial fibrillation on edoxaban: a sub-analysis from the ETNA-AF Europe registry

Outcomes of patients with atrial fibrillation on oral anticoagulation with and without heart failure: the ETNA-AF-Europe registry

The influence of atrial high-rate episodes on stroke and cardiovascular death: an update

Retrospective analysis of gastrointestinal bleedings with direct oral anticoagulants reported to EudraVigilance

Edoxaban for stroke prevention in atrial fibrillation and age-adjusted predictors of clinical outcomes in routine clinical care

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction: Main results from the PREFER in AF Prolongation Registry

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial

Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial

Uninterrupted administration of edoxaban vs vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation: Rationale and design of the ELIMINATE-AF study

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

Pharmacists' confidence when providing pharmaceutical care on anticoagulants, a multinational survey

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis From the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation)

Personalized approach to primary and secondary prevention of ischemic stroke

Zobrazit více v PubMed

ClinicalTrials.gov
NCT00781391