Warfarin Dosing Based on Genotype May Reduce Adverse Events

Risk of composite of major bleeding, INR ≥4, VTE, death down for hip, knee arthroplasty patients
Risk of composite of major bleeding, INR ≥4, VTE, death down for hip, knee arthroplasty patients

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 September 26 issue of 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 one through 11 of therapy. Overall, 808 and 789 patients in the genotype-guided and clinically-guided groups, respectively, completed the trial. 

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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 or greater, venous thromboembolism, or death; relative rate [RR], 0.73; 95% confidence interval [CI], 0.56 to 0.95). In the genotype-guided versus clinically-guided group, the number of individual events was 2 versus 4 for major bleeding (RR, 0.24; 95% CI, 0.05 to 1.15), 56 versus 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51 to 0.99), and 33 versus 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54 to 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.

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