The patient must be a new start on warfarin requiring long-term oral anticoagulation therapy and at least 65 years old. For other inclusion and exclusion criteria, see study enrollment.

The genetics of all enrollees will be determined, Some of those enrolled into the study will receive genetic testing and information on their genotype. Others-but most will receive only dosing recommendations. Once their study participation is completed the genetic information will be available to all enrollees.  

CYP2C9: The CYP2C9 gene (also known as P4502C9) encodes a member of the cytochrome (CYP) P450 super-family of enzymes, responsible for catalyzing many reactions involved in overall drug metabolism. Specifically, the CYP2C9 gene provides instruction for a liver enzyme (CYP2C9) that metabolizes the more active isomer of warfarin (S-warfarin) to inactive products. Two genetic variants are associated with decreased metabolic efficiency of the CYP2C9 enzyme and increased risk of bleeding.

VKORC1: The VKORC1 gene encodes a member of the vitamin K cycle, a necessary component in the production of key coagulation factors. Warfarin targets blood coagulation by interfering with the metabolism of vitamin K, and the reduction of available vitamin K creates an anticoagulant effect. Individuals carrying one or two variant copies of VKORC1 G>A are more sensitive to warfarin therapy and at increased risk of bleeding.

Variants in both CYP2C9 and VKORC1 are associated with lower dose requirements for warfarin.

The test requires a small (less than or equal to 4 mL) amount of blood. A blood sample will be sent to Iverson Genetic Diagnostics, where the DNA is isolated and tested using the Warfarin GenoSTAT Test to determine the subject's genotype for CYP2C9 and VKORC1. The turnaround time for test results is 24 hours from receipt at Iverson Genetic Diagnostics.

As part of the Iverson Genetic Diagnostics procedure, the patient's subject's clinical information and genetic test results are entered into the website www.warfarindosing.org. The website uses an algorithm, validated by Dr. Brian Gage at Washington University, to determine the recommended dose of warfarin. For the randomized subjects, Somehalf participants will get a dose recommendation using the genetic information and clinical factors and the other half will get a dose recommendation using clinical factors only. No one will know which group a participant is in.

The algorithm includes clinical factors such as age, sex, weight, height, smoking, liver disease, indication, as well as concomitant medication use such as Amiodarone, Statins, and Azoles.

The study participants will be followed either 30 or 90 days after their first dose of warfarin. The length of participation will depend on which group the enrollee is assigned to.  

The study will last long enough to achieve the necessary sample sizes for appropriate power. We predict this will take at least 18 months.

Yes, half of the randomized participants will receive dosing recommendations obtained using a standard clinical algorithm only (control group). Participants will be randomly assigned to either the study or control group; the physician and patient will be blinded as to which group the patient has been assigned.

All patients subjects will receive standard of care, but the study group will have their dose determined using genetic factors as well as standard practices. The patient subject will be required to give one small blood sample. All patients participants enrolled will be scheduled to be prescribed warfarin whether in the study or not.