Genotype-Based Guidance of Warfarin Dosing Has No Benefit

In the Clarification of Optimal Anticoagulation through Genetics (COAG) trial, 1015 U.S. adults were randomized to receive warfarin therapy guided for the first 5 days of dosing either by a genotype-based algorithm in addition to clinical variables or by a control protocol based only on clinical variables. Genotype data were available for 45% of participants before the first warfarin dose and for 94% before the second dose (point-of-care testing was not used). Patients and clinicians were blind to the actual dose of warfarin administered during the first 4 weeks of treatment.

By 4 weeks, the mean percentage of time spent within the therapeutic International Normalized Ratio (INR) range of 2.0 to 3.0 was similar the two groups (about 45%). The two groups also did not differ significantly in mean percentages of time spent below and above the therapeutic INR range or in the elapsed time to first therapeutic INR. Findings persisted regardless of patient sex, number of genetic variants, or predicted daily warfarin dose (<1.0 mg vs. ≥1.0 mg). However, among black patients, the mean percentage of time within the therapeutic INR range was significantly lower in the genotype-guided group than in the control group (35.2% vs. 43.5%). The two groups did not differ significantly in the incidence of adverse events or in time to any INR ≥4.0, major bleeding, or thromboembolism.