From the American College of Cardiology
Trial-and-Error Dosing Obsolete
NEW ORLEANS—Rapid, 1-hour genotype testing to guide the use of warfarin (Coumadin, Jantoven) therapy is clinically feasible and accurate, said Jeffrey L. Anderson, MD, at the American College of Cardiology annual meeting.
This rapid test should allow same-visit application of genotyping to determine the best dosage of warfarin, making the current trial-and-error method obsolete. To his knowledge, the rapid assay represents the first application of genetics to clinical practice in cardiovascular medicine.
Physicians may soon be able “to adjust the critical first loading dose of warfarin and subsequent doses based on ‘in-office’ genotyping,” said Dr Anderson, associate chief of cardiology at LDS Hospital, and professor of internal medicine, University of Utah, Salt Lake City.
Interindividual variability in the response to warfarin is partly influenced by polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes. The wide variation in response to warfarin means that, at present, physicians risk overanticoagulating patients until the appropriate dose is found. Appropriate dosing can be as little as 1 mg/day or as much as 15 mg/day.
In his clinic, 72% of patients have at least 1 of the 3 genetic variants known to influence warfarin response that requires modest reductions in warfarin dosing, Dr Anderson said.
Extracting DNA from a cheek swab, polymorphisms in the CYP2CP*2, CYP2CP*3, and VKORC1 genes were identified using rapid profiling (average turnaround time, 68 minutes). Results were compared with sequencing.
There was 100% concordance between rapid genotyping and sequencing for the VKORC1 gene variant in 139 samples, and 99% agreement between the 2 methods for variants in the CYP2C9 *2 and CYP2C9 *3 genes in 140 samples.
A large clinical study is needed to compare the effects of rapid genotyping with standard practice on the percentage of warfarin recipients who have an international normalized ratio outside of the therapeutic window.
The hope is that rapid genetic-driven dosing of medicines will usher in a new era of personalized medicine that is safer and more efficient.
Douglas P. Zipes, MD, emeritus director, cardiology division, Indiana University, Indianapolis, said the next 5 years should be an exciting time for genetic-driven cardiovascular medicine, acknowledging that many cardiac syndromes have a genetic basis, including the Brugada syndrome and long QT syndrome.
