What to Believe about Pharmacogenetic Testing for Warfarin Dosing?

It is all very confusing. The Food and Drug Administration (FDA) recommends pharmacogenetic testing to determine the correct dose of Warfarin. However, two recent large studies comparing pharmacogenetic testing against standard dosing have come to different conclusions.

Warfarin is the most common drug prescribed in the UK to prevent blood clots. It works by interfering with Vitamin K production. Before doctors prescribe Warfarin, patients take a blood test to calculate their International Normalised Ratio (INR). This shows how long it takes for their blood to clot. Other factors such as the patients’ age, sex and weight are also taken into consideration before the correct dose is determined.

Some patients do not respond to the drug well though. This is because they may have a difference in the CYP2C9 and VKORC1 genes which account for 55% of the variability in patients’ drug response. So by testing patients for these genes the correct dose can be determined.

The first study called the EU Pharmacogenetics of Anticoagulant Therapy (EU-PACT) Warfarin Study showed that after 12 weeks genotyped guided patients spent a longer time in the recommended INR range than non-genotyped patients. So, genotyped patients benefited from pharmacogenetic testing.

In contrast, a second study called the Clarification of Optimal Anticoagulation Through Genetics (COAG) Study showed that after 4 weeks there was no difference in the time spent in the recommended INR range between genotyped and non-genotyped patients. This contradicts the findings of the EU-PACT study though. So what should we believe about pharmacogenetic testing in the case of Warfarin?

Well, both studies are quite different so it may not be possible to compare the findings. Firstly, the COAG study is a double blind study whereas the EU-PACT study is not. Secondly the EU-PACT study recruited European patients whereas; the COAG study recruited African-American patients. So, there may be differences in gene variants between different ethnic groups. Finally, the COAG study was performed over a shorter time period so the results may be different if it was performed up to12 weeks like the EU-PACT study.

More studies should be carried out to determine if pharmacogenetic testing should be performed over standard dosing of Warfarin.

What do you think?

By Sarah Hoang

References:

1. Pirmohamed, M., Burnside, G., Eriksson, N. et al. (2013) A Randomized Trial of Genotype-Guided Dosing of Warfarin. N. Engl. J. Med. 369. 2294-2303.

2. Kimmel, S. E., French, B., Kasner, S. E. et al. (2013) A Pharmacogenetic Versus a Clinical Algorithm for Warfarin Dosing. N. Engl. J. Med. 369. 2283-2293.