Personalized Warfarin Dosing Reduces Risk of Adverse Events

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Patients were genotyped with hip or knee arthroplasty.
Patients were genotyped with hip or knee arthroplasty.

HealthDay News — Genotype-guided warfarin dosing is associated with reduced risk of adverse events compared with clinically-guided dosing among patients undergoing elective hip or knee arthroplasty, according to a study published in the Journal of the American Medical Association.

Brian F. Gage, MD, from Washington University in St. Louis, and colleagues genotyped patients initiating warfarin for elective hip or knee arthroplasty for polymorphisms (VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M). Participants were randomly allocated to genotype-guided (831 patients) or clinically-guided (819 patients) warfarin dosing on days 1 through 11 of therapy. Overall, 808 and 789 patients in the genotype-guided and clinically-guided groups, respectively, completed the trial.

The researchers found that 10.8% and 14.7% of the genotype-guided and clinically-guided groups, respectively, met at least 1 of the end points (composite of major bleeding, international normalized ratio [INR] of ≥ 4, venous thromboembolism, or death; relative rate [RR] 0.73; 95% CI, 0.56-0.95). In the genotype-guided versus clinically-guided group, the number of individual events was 2 vs 4 for major bleeding (RR 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of ≥ 4 (RR 0.71; 95% CI, 0.51-0.99), and 33 vs 38 for venous thromboembolism (RR 0.85; 95% CI, 0.54-1.34); there were no deaths.

"Further research is needed to determine the cost-effectiveness of personalized warfarin dosing," the authors write.

Several authors disclosed financial ties to the pharmaceutical and publishing industries; GenMarkDx loaned the eSensor genotyping platform to the central genotyping laboratory.

Reference

Gage BF, Bass AR, Lin H, et al. Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: the GIFT randomized clinical trial. JAMA. 2017:318(12):1115-1124.



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