Scientists Study Genes To Improve Warfarin Treatment

A team of international researchers, which included scientists from Liverpool and Newcastle University, developed a mathematical formula to understand how genetic information about a patient could help clinicians better predict the appropriate dosage of warfarin – one of the world’s most widely prescribed drugs.

Warfarin is used to prevent blood clots that lead to heart attacks, strokes and in extreme cases, death.  The drug is prescribed to one per cent of patients in the UK, but clinicians have found that the appropriate dose of the drug is difficult to predict because individual patients react differently to it.

Scientists developed a model based on administration of fixed drug dosages per day and standard clinical information about individual patients.  They combined this data with additional information on variations in two genes called, CYP2C9 and VKORC1, which differ slightly among individual patients and are known to influence the effectiveness of warfarin.  Researchers then compared their calculations with actual prescribed dosages, and found that by using the additional genetic information they could better predict the optimal warfarin dose for each patient.

Professor Munir Pirmohamed, from the University’s School of Biomedical Sciences, explains: “Warfarin is amongst the top three drugs responsible for hospital-related adverse drug reactions.  It is also, however, highly beneficial in preventing thrombosis and strokes, and we need to develop methods that improve the benefits and minimize the harms associated with the use of the drug.  The crucial issue is to identify the correct dose for each patient.”

Professor Farhad Kamali, from the University of Newcastle, added: “The way different patients respond to warfarin is notoriously unpredictable, particularly at the start of treatment. Now we know that certain genes can affect the way individual patients respond to warfarin, we can use this information to personalise therapy.”

Liverpool and Newcastle will join research centres across Europe in conducting randomised clinical trials of more than 2,000 new patients to better understand if the more precise, gene-based studies are the best option for patients starting drug treatment.  The trial, called EU-PACT, is due to start in October this year and patients will be recruited through doctors in the Liverpool and Newcastle region.

The warfarin studies are supported by the Department of Health. The EU-PACT trial is being supported by the EU FP7 Framework programme.