In adults undergoing hip or knee arthroplasty, is genotype-guided perioperative warfarin dosing superior to clinically guided algorithm dosing?

Genotype-guided perioperative warfarin dosing was superior to clinically guided algorithm dosing in reducing the composite outcome of major bleeding, death, venous thrombotic events, and an international normalized ratio (INR) of 4 or greater. However, the only component of the composite outcome that was significantly reduced alone was the disease-oriented outcome of the INR. The rates of occurrence of the patient-oriented outcomes (major bleeding, symptomatic deep vein thrombosis [DVT], or pulmonary embolism) were not significantly different between the 2 dosing methods. (LOE = 1b)

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.  [PMID:28973620]

Randomized controlled trial (single-blinded)

Government

Concealed

Inpatient (any location) with outpatient follow-up

Prior evidence has shown no benefit of adding genetic information to a validated clinical algorithm for warfarin management (Kimmel SE et al. NEJM 2013;369(24):2283-93). These investigators identified adults (N = 1650), 65 years or older, undergoing hip or knee arthroplasty at one of 6 US medical centers. Patients randomly received (concealed allocation assignment) either genotype-guided or clinically guided dosing of warfarin on days 1 through 11 of therapy. Warfarin dosing was guided by an online application (WarfarinDosing.org) that incorporates a standard clinical algorithm based on age, race, smoking status, body surface area, and amiodarone use. The genotype-guided algorithm added the presence or absence of specific genes affecting warfarin metabolism and sensitivity, as well as vitamin K metabolism. Individuals masked to treatment group assignment assessed the outcomes. Complete follow-up occurred for 99.9% of participants at 30 days. Using intention-to-treat analysis, the primary outcome of the composite of major bleeding, death, an INR of 4 or greater within 30 days, and a venous thrombotic event within 60 days, occurred significantly less in the genotype-guided group than in the clinically guided dosing group (10.8% vs 14.7%, respectively; number needed to treat = 25.4; 95% CI 13.8 - 150.6). However, rate differences for individual adverse events were not significant for any of the subgroups with the exception of the INR measurement. In addition, the rate of symptomatic major adverse events (major bleeding, symptomatic DVT, or pulmonary embolism) was not significantly different between the 2 treatment groups.