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

Nagler, Michael; Angelillo, Anne; 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, Nicolas and Aujesky, Drahomir (2017). Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists. Journal of thrombosis and haemostasis, 15(11), pp. 2165-2175. Wiley-Blackwell 10.1111/jth.13810

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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 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 (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. While genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence. This article is protected by copyright. All rights reserved.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern

UniBE Contributor:

Nagler, Michael; Angelillo, Anne; Méan Pascual, Marie; Limacher, Andreas; Kucher, Nils; Rodondi, Nicolas and Aujesky, Drahomir

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1538-7836

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

29 Aug 2017 14:34

Last Modified:

24 Aug 2018 02:30

Publisher DOI:

10.1111/jth.13810

PubMed ID:

28834238

Uncontrolled Keywords:

Venous Thromboembolism anticoagulants cytochrome P-450 CYP2C9 mortality phenprocoumon / Angelillo-Scherrer Anne / Nagler Michael

BORIS DOI:

10.7892/boris.105164

URI:

https://boris.unibe.ch/id/eprint/105164

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