Dosing of warfarin can be inconsistent for a variety of clinical reasons and may also be influenced by patient genotype. Significant interest exists in finding more effective ways to dose warfarin but previous studies of genotype dosing have shown varied results. The Genetic Informatics Trial (GIFT) of Warfarin to Prevent DVT seeks to determine whether genotype-guided dosing improves the safety of warfarin initiation, defined as days 1-11 of warfarin administration.
The study randomized 1650 patients aged 65 years or older starting warfarin for elective hip or knee arthroplasty to genotype-guided versus clinically guided dosing of warfarin. Compared to the standard clinically guided dosing group, the genotype-based dosing group showed a reduced rate from of major bleeding, INR of 4 or greater, venous thromboembolism, or death, (14.7% vs 10.8% for composite outcome; absolute risk difference of 3.9%, p = 0.02). Though the absolute number of events was generally small for all outcomes and there were no statistically significant differences in any individual adverse events. Use of genotype guided dosing also significantly increased the percentage of time in the therapeutic range, with the greatest increase seen in a high risk subgroup whose predicted warfarin dosing differed by 1mg or greater per day in the two treatment arms.
Genotype guided warfarin dosing had a greater reduction on adverse outcomes compared to clinically guided dosing in this study of adults 65 and older undergoing elective hip or knee arthroplasty treated with perioperative warfarin. However, the absolute reduction was primarily related to reduction in the frequency of INR values greater than 4; the reduction in major clinical events did not achieve statistical significance, which raises questions regarding the cost effectiveness of genotype-guided dosing, an aspect not examined in the current analysis.
Summarized by Elizabeth Kaplan1, James M. McCabe2
1Department of Medicine, University of Washington, Seattle, WA
2 Division of Cardiology, University of Washington, Seattle, WA
► Gage B, Bass A, Lin H, et al. Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty. JAMA. 2017;318(12):1115-1124.
Competing interests: None declared.