Using genetics to guide warfarin dosing after hip, knee replacement

September 26, 2017

Among patients undergoing hip or knee replacement and treated with the blood thinner warfarin, customizing dosing to a patient's genetic and clinical profile resulted in the prevention of more adverse outcomes than clinically-guided dosing, according to a study published by JAMA.

For at least the last 10 years, warfarin use has accounted for more medication-related emergency department visits among older patients than any other drug. Warfarin dose requirements vary widely among individuals because of common genetic variants. Because knowledge of a patient's genotype should lead to more accurate warfarin initiation and a reduction in adverse events, the product label for warfarin (Coumadin and others) has encouraged genotype-guided dosing since 2007. However, multicenter studies of genotype-guided dosing of oral vitamin K antagonists have had mixed results. Thus, it was unclear whether genotype-guided dosing could improve the safety of warfarin initiation.

Brian F. Gage, M.D., M.Sc., of Washington University in St. Louis, and colleagues randomly assigned patients ages 65 years or older initiating warfarin for elective hip or knee replacement to genotype-guided or clinically-guided warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. Patients were genotyped for certain genetic variants.

Among 1,650 randomized patients, 97 percent received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically-guided group). A total of 87 patients (10.8 percent) in the genotype-guided group vs 116 patients (14.7 percent) in the clinically guided warfarin dosing group met at least one of the end points (major bleeding, INR of 4 or greater, venous thromboembolism or death). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding, 56 vs 77 for INR of 4 or greater, and 33 vs 38 for venous thromboembolism; there were no deaths.

The study notes some limitations, including that the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.

"Further research is needed to determine the cost-effectiveness of personalized warfarin dosing," the authors write.
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For more details and to read the full study, please visit the For The Media website.

(doi:10.1001/jama.2017.11463)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

The JAMA Network Journals

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