Using genetic information to dose warfarin did not lead to better control of therapeutic levels, a study published online Nov. 19 in The New England Journal of Medicine found. The findings were simultaneously presented at the American Heart Association scientific session in Dallas.
In the Clarification of Optimal Anticoagulation through Genetics (COAG) trial, investigators randomized 1,015 patients starting warfarin between 2009 and 2013 at 18 centers in the U.S. to warfarin dosing based on clinical variables or clinical variables plus genetic information. The average follow-up time was six months. The primary endpoint was the percentage of time the international normalized ratio (INR) was therapeutic from day four or five through day 28.
Based on information from the FDA, labeling of warfarin was updated to suggest that variations in the CYP2C9 and VKORC1 gene be considered when dosing the drug; the authors performed genotype analysis to test for these variants.
The investigators, led by Stephen E. Kimmel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, found that at the 28-day mark, there was no significant difference between the two groups in terms of the primary outcome. The average percentage of time INR was therapeutic was 45.2 percent in the clinical variable-only group and 45.4 percent in the clinical variable plus genetic information group.
There was a significant difference between the groups with regard to race, however. The average time in the therapeutic range was lower in the clinical variable plus genetic information group among black patients, and the result was the opposite among non-black patients.
This race-related finding could be due to chance, the authors noted, but it could also be because of race-based differences in the response to warfarin.
Despite the findings, Kimmel said the research is still valuable.
“This study demonstrates that until you do a clinical trial, you really don’t know what the answer is going to be,” he said in a release. “There’s a lot of debate about when to bring genetics into clinical practice, and whether or not you need clinical trials before widely using genetics. For a drug as complex as warfarin, the COAG trial demonstrates the utility of performing such trials.”