Genotyping Provides No Additional Benefit in Warfarin Dosing

A recent clinical study found that combining genetic data with clinical information to determine initial warfarin dosing was no more effective than using only clinical information, according to the Clarification of Optimal Anticoagulation through Genetics (COAG) trial presented today at the American Heart Association (AHA) Scientific Sessions. 

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The trial also found that anticoagulation control in African-Americans was lower in the genetics-based approach vs. the clinically-based method.

Proper warfarin dosing can be difficult due to its many drug-drug and drug-food interactions. 

Doctors often start with a standard dose and later adjust the dose based on certain clinical measures. These clinical measures include age, body size, smoking status, and use of certain medications. 

Warfarin activity is closely monitored through blood test and adjustments are made as needed.

Research has suggested that variants of CYP2C9 and VKORC1 may be important in selecting the dose of warfarin needed for individual patients. Pharmacogenetic dosing formulas have also been developed to integrate a patient's genetic profile and clinical characteristics to better predict an appropriate dose.

The COAG trial enrolled 1,015 patients initiating warfarin therapy and randomized them to one of two dosing strategies. During the first five days of therapy, patients had their dosages determined and adjusted by a clinical formula or a pharmacogenetic formula. The participants were monitored for another 23 days, and doses were adjusted using a standard approach.

Across all patients, both the clinical and pharmacogenetic groups were similar at 45.4% and 45.2% time in therapeutic range during the 28-day phase, respectively. 

Among the African-American participants (n=255), the pharmacogenetic formula group demonstrated only 35.2% time in therapeutic range vs. 43.5% for the clinical formula. Moreover, African-Americans in the pharmacogenetic group generally took longer to reach an ideal dose (70% at Day 14) compared to the clinical group (87%).

The study was published in the New England Journal of Medicine.

For more information call (301) 592-8573 or visit the NHLBI website.

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