May 2010: Volume 36, Number 5
Warfarin Sensitivity Testing Cuts Hospitalization Rates
In the first large-scale prospective study designed to determine the clinical effectiveness of genotype testing for warfarin sensitivity, researchers from Mayo Clinic and Medco Research Institute found that the incidence of hospitalizations dropped nearly one-third when clinicians had access to patients’ test results. Some 2 million individuals start warfarin therapy each year in the U.S., but incorrect dosing sends as many as 20% to the hospital for adverse events within 6 months of initiating the anticoagulation therapy.
The study involved 896 participants with an average age of 65 who were members of prescription benefit plans managed by Medco. Hospitalization rates for this group were matched against a historical control group of 2,688 individuals. Researchers collected DNA from either blood or buccal cells and determined patients’ genotypes for the CYP2C9 and VKORC genetic variants. Mutations in the CYP2C9 gene have been associated with decreased warfarin metabolism, while mutations in the VKORC1 gene are associated with warfarin sensitivity. Based on each individual’s genotype, clinicians used a dosing algorithm to determine that person’s initial dose. The study followed patients for 6 months after the start of their treatment. Compared with the control group, the genotyped patients had 31% fewer hospitalizations overall and 28% fewer hospitalizations for bleeding or thromboembolism during the follow-up period.
|
Snapshot
Warfarin Sensitivity |
| |
Allelic Frequencies |
| |
Caucasian |
Asian |
African
American |
VKORC1
(1639G>A) |
42% |
89% |
8% |
CYP2C9
(430C>T) |
8–13% |
2–6% |
<1% |
CYP2C9
(1079A>C) |
6–10% |
<1% |
1–4% |
| Source: ARUP Laboratories |
The research team concluded that genotyping before determining warfarin dosage can reduce the risk of consequent hospitalizations. Robert Epstein, MD, president of Medco Research Institute and lead author of the study, stated in a press release, “These results show that we can greatly reduce hospitalizations, and their significant costs, by making genetic testing routine early in a patient's therapy with warfarin.”
The study results were first reported at the American College of Cardiology’s annual meeting in March and are now available online: J Am Coll Cardiol (doi:10.1016/j.jacc.2010.03.009).