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Title: Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: A randomized controlled trial
Authors: Syn N.L.
Wong A.L.-A. 
Lee S.-C. 
Teoh H.-L. 
Yip J.W.L. 
Seet R.C.S. 
Yeo W.T. 
Kristanto W.
Bee P.-C.
Poon L.M. 
Marban P. 
Wu T.S.
Winther M.D.
Brunham L.R.
Soong R. 
Tai B.-C.
Goh B.-C. 
Keywords: Anticoagulants
Cytochrome P450
Precision medicine
Issue Date: 10-Jul-2018
Publisher: BioMed Central Ltd.
Citation: Syn N.L., Wong A.L.-A., Lee S.-C., Teoh H.-L., Yip J.W.L., Seet R.C.S., Yeo W.T., Kristanto W., Bee P.-C., Poon L.M., Marban P., Wu T.S., Winther M.D., Brunham L.R., Soong R., Tai B.-C., Goh B.-C. (2018-07-10). Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: A randomized controlled trial. BMC Medicine 16 (1) : 104. ScholarBank@NUS Repository.
Abstract: Background: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. Methods: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90days. The primary efficacy measure was the number of dose titrations within the first 2weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14days of therapy. Results: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P<0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P=0.001), but not frequency of INR measurements, was lower at 1, 2, and 3months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R 2 =42.4% (P<0.001) and mean percentage error of -7.4%. Conclusions: Among Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients. © 2018 The Author(s).
Source Title: BMC Medicine
ISSN: 1741-7015
DOI: 10.1186/s12916-018-1093-8
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