Clinical and Economic Consequences of Pharmacogenetic-guided Dosing of Warfarin

Talitha I Verhoef; Tom Schalekamp; William K Redekop; Anthonius de Boer; Anke-Hilse Maitland-van der Zee


Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(4):375-378. 

In This Article

Expert Commentary & Five-year View

Pharmacogenetic-guided dosing of warfarin and other coumarin derivatives seems to be a promising new method to improve the safety and efficacy of oral anticoagulant therapy. Currently, the response to warfarin treatment is evaluated by INR measurement after the first few days of therapy. The prescribed dose can then be adapted to the patient's needs, so the patient will receive a more individualized dose after this first INR measurement. However, in the first few days of therapy, no information on the patient's response is available, so all patients receive the same loading dose. If patients were to be genotyped before they started taking warfarin, the loading dose for the first few days could already be personalized. However, this would only be possible if the genotype results are available before warfarin initiation. Therefore, it is desirable to have a fast, reproducible and accurate method to genotype; for this purpose, point-of-care testing might be useful.

Meckley et al. have shown that pharmacogenetic-guided dosing could improve health at higher healthcare costs compared with standard care, but there is not enough information available yet on the effectiveness of this genotype-guided dosing method.[1] Moreover, as the study of You et al.[5] demonstrates, a low adverse event rate with warfarin therapy will make genotyping less cost effective. As a consequence, the cost–effectiveness of pharmacogenetic-guided warfarin dosing will differ between countries and will be particularly favorable in settings where warfarin therapy is complicated by a relatively high rate of bleedings and thromboembolic events. The upcoming use of direct thrombin inhibitors might also reduce the value of genotype-guided warfarin dosing in the future to some extent.

It is not yet fully known how to use the genetic information to adjust the prescribed warfarin dose. In the study of Meckley et al. it seemed that patients with a variant genotype were underdosed in the pharmacogenetic-guided dosing strategy.[1] Dosing algorithms, such as the dosing algorithm developed by the International Warfain Pharmacogenetics Consortium,[10] therefore need to be developed and tested widely to find the optimal way of adjusting the dose of warfarin or other coumarin derivatives according to the genetic information. It is also not yet clear whether the genetic information has any value for determining the right dose after the first few days of therapy, when the dose is also adjusted according to the INR values of the patients.

Within a few years, more data on this subject will become available, as several large clinical trials investigating the effectiveness of pharmacogenetic-guided dosing algorithms in treatment with warfarin and other coumarin derivatives are now underway.[11,101] Since the primary outcome of these studies is time within therapeutic INR range, a model like the one presented in this study of Meckley et al.[1] would be very useful to assess not only the effectiveness but also the cost–effectiveness of a pharmacogenetic-guided dosing strategy.


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