A Randomized Trial of Genotype-Guided Dosing of Warfarin

被引：636

作者：

Pirmohamed, Munir ^{[1
,2
]}

Burnside, Girvan ^{[1
]}

Eriksson, Niclas ^{[6
,7
]}

Jorgensen, Andrea L. ^{[1
]}

Toh, Cheng Hock ^{[1
,2
]}

Nicholson, Toby ^{[3
]}

Kesteven, Patrick ^{[4
]}

Christersson, Christina ^{[6
,8
]}

Wahlstrom, Bengt ^{[8
]}

Stafberg, Christina ^{[9
]}

Zhang, J. Eunice ^{[1
]}

Leathart, Julian B. ^{[5
]}

Kohnke, Hugo ^{[6
]}

Maitland-van der Zee, Anke H. ^{[10
]}

Williamson, Paula R. ^{[1
]}

Daly, Ann K. ^{[5
]}

Avery, Peter ^{[5
]}

Kamali, Farhad ^{[5
]}

Wadelius, Mia ^{[6
,8
]}

机构：

[1] Univ Liverpool, Liverpool L69 3GL, Merseyside, England

[2] Royal Liverpool & Broadgreen Univ Hosp Natl Hlth, Liverpool, Merseyside, England

[3] Whiston Hosp, Prescot, Merseyside, England

[4] Newcastle Upon Tyne NHS Trust, Newcastle Upon Tyne, Tyne & Wear, England

[5] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[6] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[7] Uppsala Clin Res Ctr, Uppsala, Sweden

[8] Univ Uppsala Hosp, Uppsala, Sweden

[9] Enkoping Hosp, Enkoping, Sweden

[10] Univ Utrecht, Utrecht, Netherlands

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 369卷 / 24期

基金：

瑞典研究理事会; 英国医学研究理事会;

关键词：

VKORC1; GENOTYPES; PHARMACOGENETICS; CYP2C9; THERAPY; FUTURE; RISK; CARE;

D O I：

10.1056/NEJMoa1311386

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. MethodsWe conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639GA) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. ResultsA total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). ConclusionsPharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.)

引用

页码：2294 / 2303

页数：10

共 30 条

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