Real-time genotype-based warfarin dosing feasible, but not linked to fewer out-of-range INRs

November 7, 2007

Real-time pharmacogenetic-guided dosing of warfarin does not lead to a reduction in prothrombin time international normalized ratios (INRs) out of the therapeutic range compared with standard warfarin dosing, although it did lead to smaller and less frequent warfarin dosing changes, reported Jeffrey L. Anderson, MD.

Real-time pharmacogenetic-guided dosing of warfarin does not lead to a reduction in prothrombin timeinternational normalized ratios (INRs) out of the therapeutic range compared with standard warfarindosing, although it did lead to smaller and less frequent warfarin dosing changes, reported JeffreyL. Anderson, MD.

Previous research identified variants in CYP2C9 and VKORC1 genes that partly influence the variationin response to warfarin.

The 206 warfarin recipients in this study were randomized in a double-blind fashion to genotype-basedwarfarin dose initiation and maintenance or to a standard, empiric dosing algorithm.

DNA was extracted from a buccal swab to identify polymorphisms in the CYP2CP*2 and *3 and the VKORC1genes, using rapid profiling.

The study showed that rapid genotyping to guide anticoagulation therapy in "real time" was feasible.Pharmacogenetic-guided dosing resulted in more stable dosing (P P=.002) and fewer (P=.06) dose changes compared with empiric dosing.

However, the out-of-range INRs, which was the primary endpoint of the study, did not differsignificantly between the two arms (pharmacogenetic = 30.7%; standard = 33.1%).

In a subset analysis of the primary endpoint, the percentage of INRs out of range was significantlyless (P =.03) when confined to the patients with wild-type or multiple variant carriers(pharmacogenetic = 29.3%; standard 39.1%).

According to Dr Anderson, associate chief of cardiology at LDS Hospital, University of Utah, SaltLake City, rapid genotyping still holds promise as a means to deliver personalized medicine, but theprecise setting and patient groups in which it will be most helpful still need to beidentified.

He said that outcomes were better than expected in the standard dosing arm because the majority ofthis group had careful management of dosing by a dedicated anticoagulation service, with initialdaily INR measurement common.

The study was published simultaneously to Dr Anderson's presentation at the American HeartAssociation Scientific Sessions in Circulation.