Genetics failed to take the guesswork out of warfarin dosing
American Heart Association Late-Breaking Clinical Trial Report LBCT 5/Abstract: 19535 (Hall E)
- Genetic testing did not prove useful in improving blood thinning control in patients on warfarin.
- Both the group undergoing genetic testing and the standard dosing group were within the appropriate therapeutic range — meaning that the blood thinning was within the desired level — 45 percent of the time.
DALLAS, Nov. 19, 2013 — Genetics did not prove useful in predicting optimal doses of warfarin for patients in a late-breaking clinical trial presented at the American Heart Association’s Scientific Sessions 2013.
In the Clarification of Optimal Anticoagulation through Genetics (COAG) trial, researchers divided 1,015 patients with histories of stroke, venous thrombosis and atrial fibrillation, who took the common blood-thinning drug warfarin into two groups. Clinical information, such as age, weight, and smoking status, was used for one group to measure how much warfarin they would need while the second group used similar clinical information plus genetics.
During this multi-center, randomized, double-blinded, controlled study, all patients received warfarin, but one group received therapy based on clinical information, while the other group received therapy guided by their genetic information. Each group received an initial warfarin dose, and then four to five days later, adjustments were made to their doses based on either genetic information or standard clinical information.
Patients were followed for up to six months from 2009-2013.
Regardless of whether or not genetic information was used, the two groups of patients showed no significant differences in outcomes; both groups were within the appropriate therapeutic range — meaning that the blood thinning was within the desired range — 45 percent of the time over the first four weeks. In an additional finding among African Americans, those receiving therapy based on genetics didn’t do as well as those who did not use genetics.
Patients’ average age was 57 years; 51 percent were male; 27 percent were African American; 22 percent had atrial fibrillation, and 58 percent had deep vein thrombosis in the legs or lungs.
“This study demonstrates that until you do a clinical trial, you really don't know what the answer is going to be," said Stephen Kimmel, M.D., lead study author and a professor of medicine and epidemiology at the University of Pennsylvania School of Medicine. "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.”
Predicting the right dose of warfarin for the individual patient can be tricky; too much can lead to internal bleeding and too little can lead to blood clots, some of which can be life-threatening. Patients taking warfarin have to undergo frequent monitoring to see whether their doses need to be changed. Identifying certain genetic markers from a patient's blood sample is suggested to help improve the initial dosing of warfarin and smooth out the many dose changes often required during monitoring.
One gene is responsible for how warfarin is metabolized by the liver. The other gene is about how the body responds to warfarin. Identifying one or both of these two genes in a patient's blood sample has been suggested to help physicians prescribe more specific warfarin doses that better align with the patient's unique biological makeup.
Co-authors are Benjamin French Ph.D.; Scott E. Kasner, M.D.,M.S.C.E.; Julie A. Johnson, Pharm.D.; Jeffrey L. Anderson, M.D.; Brian F. Gage, M.D., M.Sc.; Yves D. Rosenberg, M.D., M.P.H.; Charles S. Eby, M.D., Ph.D.; Rosemary A. Madigan, R.N., M.P.H.; Robert B. McBane, M.D.; Sherif Z. Abdel-Rahman, Ph.D.; Scott M. Stevens, M.D.; Steven Yale, M.D.; Emile R. Mohler, III, M.D.; Margaret C. Fang, M.D., M.P.H.; Vinay Shah, M.D.; Richard B. Horenstein, M.D.; Nita A. Limdi, Pharm.D., Ph.D., M.S.P.H.; James A. S. Muldowney, III, M.D.; Jaspal Gujral, M.B.B.S.; Patrice Delafontaine, M.D.; Robert J. Desnick, M.D., Ph.D.; Thomas L. Ortel, M.D., Ph.D.; Henny H. Billett, M.D., M.Sc.; Robert C. Pendleton, M.D.; Nancy L. Geller, Ph.D.; Jonathan L. Halperin, M.D.; Samuel Z. Goldhaber, M.D.; Michael D. Caldwell, M.D., Ph.D.; Robert M. Califf, M.D. and Jonas H. Ellenberg, Ph.D., Disclosures
The National Heart, Lung, and Blood Institute funded the study. GenMark Diagnostics and AutoGenomics Inc. loaned genotype platforms to the study and Bristol-Meyers Squibb donated the study drug.
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Note: Actual presentation is 11:17 a.m. CT/12:17 p.m. ET, Tuesday, Nov. 19, 2013 in Hall E.
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