Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

Shaw, Kaitlyn; Amstutz, Ursula; Kim, Richard B; Lesko, Lawrence J; Turgeon, Jacques; Michaud, Veronique; Hwang, Soomi; Ito, Shinya; Ross, Colin; Carleton, Bruce C (2015). Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy. Therapeutic drug monitoring, 37(4), pp. 428-436. Lippincott Williams & Wilkins 10.1097/FTD.0000000000000192

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OBJECTIVE To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. RESULTS Testing of VKORC1 (-1639G>A), CYP2C9*2, and CYP2C9*3 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C9*5, *6, *8, or *11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. SIGNIFICANCE This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Amstutz, Ursula

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0163-4356

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Ursula Amstutz

Date Deposited:

10 Aug 2015 15:48

Last Modified:

01 Sep 2016 02:30

Publisher DOI:

10.1097/FTD.0000000000000192

PubMed ID:

26186657

BORIS DOI:

10.7892/boris.70720

URI:

https://boris.unibe.ch/id/eprint/70720

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