Genetic Testing for Warfarin Sensitivity Reduced Hospitalizations

Genetic testing as part of initial management of patients going on warfarin reduced hospitalizations by nearly 30% compared with patients initiated on warfarin who were not tested, according to results of a large national study called the Medco-Mayo Warfarin Effectiveness Study (MM-WES) presented at the 59th Annual Scientific Session of the American College of Cardiology. Further, the sooner genetic test results were available upon warfarin initiation, the better the outcomes.

As a result of the genotyping test, physicians modified warfarin prescribing, and physician acceptance of genotyping was high, in the order of 75%, said Robert S Epstein, MD, who presented results of the MM-WES at a late-breaking clinical trials session during the 59th Annual Scientific Session of the American College of Cardiology. Epstein is Chief Medical Officer and President of the Medco Research Institute in Franklin Lakes, NJ.

“It is challenging to get patients on a stable dose of warfarin. Warfarin can cause drug-related morbidity and mortality. No study has looked at the effect of genotyping on outcomes, although a meta-analysis of three studies showed reduced bleeding with warfarin in patients who were genotyped. Our study looked at outcomes using a genetic test for two genes that account for the variance in warfarin dosing: cytochrome P450 2C9 [CYP2C9] and VKORC1,” Epstein told listeners.

The primary comparison of the study was based on 896 patients beginning warfarin therapy who were genotyped compared with 2688 patients starting warfarin without genotyping during the same time period. Subjects were recruited from prescription benefit plans managed by Medco Health Solutions in 49 states in the US. Patients were followed for six months.

Mean age of patients was 60.5 years. Both the intervention and the historical control groups had similar demographics, and no significant differences were observed for percentages of patients taking different concomitant cardiovascular medications and those with various medical conditions necessitating warfarin (ie, gastrointestinal bleed, atrial fibrillation, pulmonary embolism, deep vein thrombosis). Significantly more patients in the genotype test group had hypertension (54.2% versus 47%, respectively, P<.001).

Within 21 days of genotyping, 29% of patients were found to have below normal warfarin sensitivity, 25% to have moderate sensitivity, 4% to have high sensitivity, and 2.4% to have very high sensitivity. Warfarin doses were adjusted according to test results.

At six months, hospitalization rates were significantly reduced by 28% in the genotype group for all-cause hospitalizations (25.2% vs. 18.45% in the genotype group, P<.001); hospitalizations due to bleed or thromboembolism were also reduced by 27% with the use of genotyping (8.13% versus 5.97%, respectively). This was based on an Intent-to-Treat analysis, which included all patients assigned to genotyping whether or not they actually had the test, Epstein explained.

The study was sponsored by Medco and the Mayo Clinic Center for Individualized Therapy.