Warfarin-Associated Adverse Events Reduced by Genotype-Guided Dosing

Genotype-guided warfarin dosing reduced the risk of major bleeding and other medication-related adverse events among older patients undergoing elective hip or knee arthroplasty, according to a recent study.

In the randomized clinical trial, the researchers genotyped 1650 patients who were initiating warfarin prior to elective hip or knee arthroplasty (mean age 72.1 years). A total of 831 patients were randomly assigned to genotype-guided warfarin dosing and 819 patients were randomly assigned to clinically guided warfarin dosing for 11 days and to a target international normalized ratio (INR) of either 1.8 or 2.5. In addition, patients underwent screening of lower-extremity duplex ultrasound about 1 month after surgery.
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The composite of major bleeding, INR of 4 or more, venous thromboembolism or death was assessed as the primary endpoint.

Overall, 1597 (96.8%) patients completed the trial, with 808 patients in the genotype-guided group and 789 patients in the clinically guided group.

At least 1 of the endpoints was observed in 87 patients (10.8%) in the genotype-guided group and 116 (14.7%) in the clinically guided group. Among those in the genotype-guided group, 2 patients experienced major bleeding, 56 had INR of 4 or more, and 33 had venous thromboembolism compared with 8 patients, 77 patients, and 38 patients in the clinical guided group, respectively. However, no patients died.

“Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death,” the researchers concluded. “Further research is needed to determine the cost-effectiveness of personalized warfarin dosing.”

—Melissa Weiss

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 [published online September 26, 2017]. JAMA. doi:10.1001/jama.2017.11469.