Safety of direct oral anticoagulants in patients with advanced liver disease.
Liver Int
; 41(9): 2159-2170, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34152697
ABSTRACT
BACKGROUND & AIMS:
While direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.METHODS:
Liver disease patients receiving DOAC treatment (ACLD n = 104; vascular liver disease n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD n = 45; vascular n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients.RESULTS:
Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months 36.9% vs CPS-A 15.9%, subdistribution hazard ratio [SHR] 3.23 [95% CI 1.59-6.58], P < .001), as were major bleedings (at 12 months 22.0% vs 5.0%, SHR 5.82 [95% CI 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR 4.12 [91% CI 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI 169-395] vs CPS-A 137 [95% CI 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.CONCLUSIONS:
Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Heparina de Baixo Peso Molecular
/
Hepatopatias
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Áustria