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Sökning: WFRF:(Williamson Peter R) > (2010-2014) > A Randomized Trial ...

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FältnamnIndikatorerMetadata
00004016naa a2200481 4500
001oai:DiVA.org:uu-216750
003SwePub
008140124s2013 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2167502 URI
0247 a https://doi.org/10.1056/NEJMoa13113862 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Pirmohamed, Munir4 aut
2451 0a A Randomized Trial of Genotype-Guided Dosing of Warfarin
264 1c 2013
338 a print2 rdacarrier
500 a Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.
520 a Background: The 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.Methods: We 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.Results: A 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).Conclusions: Pharmacogenetic-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. 
7001 a Burnside, Girvan4 aut
7001 a Eriksson, Niclasu Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)nieri103
7001 a Jorgensen, Andrea L.4 aut
7001 a Toh, Cheng Hock4 aut
7001 a Nicholson, Toby4 aut
7001 a Kesteven, Patrick4 aut
7001 a Christersson, Christinau Uppsala universitet,Institutionen för medicinska vetenskaper4 aut0 (Swepub:uu)chchr086
7001 a Wahlström, Bengtu Uppsala universitet,Institutionen för medicinska vetenskaper4 aut
7001 a Stafberg, Christina4 aut
7001 a Zhang, J. Eunice4 aut
7001 a Leathart, Julian B.4 aut
7001 a Kohnke, Hugo4 aut
7001 a Maitland-van der Zee, Anke H.4 aut
7001 a Williamson, Paula R.4 aut
7001 a Daly, Ann K.4 aut
7001 a Avery, Peter4 aut
7001 a Kamali, Farhad4 aut
7001 a Wadelius, Miau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)miawadel
7102 a Uppsala universitetb Institutionen för medicinska vetenskaper4 org
7730 t New England Journal of Medicineg 369:24, s. 2294-2303q 369:24<2294-2303x 0028-4793x 1533-4406
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-216750
8564 8u https://doi.org/10.1056/NEJMoa1311386

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