Edoxaban Versus Warfarin in Patients With Atrial Fibrillation and History of Liver Disease.
J Am Coll Cardiol
; 74(2): 179-189, 2019 07 16.
Article
em En
| MEDLINE
| ID: mdl-31296289
ABSTRACT
BACKGROUND:
Patients with liver disease have increased risk of thrombosis and bleeding but are typically excluded from trials of direct oral anticoagulant agents.OBJECTIVES:
This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy and safety of edoxaban versus warfarin in patients with atrial fibrillation (AF) and history of liver disease.METHODS:
ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction Study 48) was a randomized, double-blind trial comparing edoxaban with warfarin in patients with AF followed for 2.8 years. History of liver disease was defined as investigator-reported liver disease or >2-fold transaminase elevation at randomization. The primary efficacy and safety endpoints of stroke or systemic embolic event (SSEE) and major bleeding were assessed stratified by history of liver disease. PK/PD assessments of edoxaban included endogenous and extrinsic factor Xa activity and edoxaban concentration.RESULTS:
Among 21,105 patients, 1,083 (5.1%) had a history of liver disease; they had a higher prevalence of many comorbidities. The adjusted risks of SSEE were similar (adjusted hazard ratio [HRadj] 0.90; 95% confidence interval [CI] 0.67 to 1.22; p = 0.50), but major bleeding was more common in patients with liver disease (HRadj 1.38; 95% CI 1.10 to 1.74; p = 0.005). There were no significant differences in PK/PD assessment of edoxaban in patients with versus without liver disease. The HRs for higher-dose edoxaban versus warfarin for SSEE were 0.86 (95% CI 0.73 to 1.01) in patients without and 1.11 (95% CI 0.54 to 2.30) with liver disease (p for interaction [pint] = 0.47), major bleeding 0.80 (95% CI 0.70 to 0.91) in patients without and 0.91 (95% CI 0.56 to 1.47) with liver disease (pint = 0.63). There were no significant differences in hepatic adverse events between the 2 treatment groups.CONCLUSIONS:
Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease. A history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin. Hepatic adverse events were similar between edoxaban and warfarin.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Fibrilação Atrial
/
Tiazóis
/
Varfarina
/
Acidente Vascular Cerebral
/
Embolia
/
Inibidores do Fator Xa
/
Hepatopatias
/
Anticoagulantes
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article