Scientists study genes to improve warfarin treatment

Scientists at the University of Liverpool have found that information about a patient¿s genes could help increase the effectiveness of drugs such as warfarin.

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 and the research is published in the New England Journal of Medicine. The EU-PACT trial is being supported by the EU FP7 Framework programme.

Notes to editors:

1. Information for patients:
“¢ If members of the public have any concerns about their medication they should seek advice from their GP, or from their anticoagulant clinic
“¢ Warfarin has known benefits, and therefore patients should not stop drugs of their own accord without advice from their doctor 
“¢ Regular monitoring and adherence to the prescribed dose, together with a regular diet, avoidance of excessive amounts of alcohol and interacting medications, can help in preventing problems with warfarin.

2. The University of Liverpool is developing a £10 million Centre for Personalised Medicines where scientists will work to pioneer a major initiative to establish a clinical evidence base for safe and effective medication based on a patient’s unique genetic make-up and other factors such as age, weight and diet.  The Centre will be housed in the former Liverpool Royal Infirmary which is being renovated following a substantial gift from The Wolfson Foundation. The University is also home to the country’s first and only NHS Chair in Pharmacogenetics – a position held by Professor Munir Pirmohamed, who leads a team of scientists in testing medication for illnesses such as epilepsy and asthma.

3. Scientists at the Universities of Liverpool and Manchester, supported by the Medical Research Council (MRC), have developed a Centre for Drug Safety aimed at reducing the risks of adverse drug effects.  Working with leading pharmaceutical companies, scientists aim to improve understanding of adverse drug reactions and investigate how to improve the design, tailoring and selection of drugs, with the aim of developing new medicines for the future. 

4. The University of Liverpool is a member of the Russell Group of leading research-intensive institutions in the UK. It attracts collaborative and contract research commissions from a wide range of national and international organisations valued at more than £93 million annually.

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