Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists.

Détails

ID Serval
serval:BIB_83E81F84DC7C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists.
Périodique
Journal of thrombosis and haemostasis
Auteur(s)
Nagler M., Angelillo-Scherrer A., Méan M., Limacher A., Abbal C., Righini M., Beer J.H., Osterwalder J., Frauchiger B., Aschwanden M., Matter C.M., Kucher N., Cornuz J., Banyai M., Husmann M., Staub D., Mazzolai L., Hugli O., Rodondi N., Aujesky D.
ISSN
1538-7836 (Electronic)
ISSN-L
1538-7836
Statut éditorial
Publié
Date de publication
11/2017
Peer-reviewed
Oui
Volume
15
Numéro
11
Pages
2165-2175
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: ppublish
Résumé
Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only.
Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.
Mots-clé
Age Factors, Aged, Anticoagulants/adverse effects, Anticoagulants/therapeutic use, Blood Coagulation/drug effects, Cytochrome P-450 CYP2C9/genetics, Cytochrome P-450 CYP2C9/metabolism, Female, Hemorrhage/chemically induced, Humans, Male, Pharmacogenetics, Pharmacogenomic Variants, Prospective Studies, Recurrence, Risk Factors, Switzerland, Time Factors, Treatment Outcome, Venous Thromboembolism/blood, Venous Thromboembolism/drug therapy, Venous Thromboembolism/genetics, Venous Thromboembolism/mortality, Vitamin K/antagonists & inhibitors, Vitamin K Epoxide Reductases/genetics, Vitamin K Epoxide Reductases/metabolism, anticoagulants, cytochrome P-450 CYP2C9, mortality, phenprocoumon, venous thromboembolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/11/2017 19:10
Dernière modification de la notice
08/05/2019 21:17
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