The PEP-WARF Study
Research type
Research Study
Full title
Developing Dosing Algorithms In Patients With Extreme Phenotypes Who Require Anticogaulation With Warfarin.
IRAS ID
151001
Contact name
Munir Pirmohamed
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
1 years, 11 months, 29 days
Research summary
Warfarin is the most widely used oral anticoagulant worldwide with overwhelming efficacy for its use in the management of thromboembolic disease. Warfarin is complicated by unpredictability in anticoagulation response due to its wide inter-individual dose variability. Adverse effects include thrombosis or bleeding caused by either under- or over-dosing respectively. This necessitates careful monitoring by measurement of the International Normalised Ratio (INR). Research has shown that 40% of individual dose variability can be explained by two genes (CYP2C9 and VKORC1). Several pharmacogenetic dosing algorithms have been developed with clinically superior results in terms of time spent within therapeutic range and a trend towards a reduction in major bleeding events.
Several new oral anticoagulants have been developed however, despite receiving approval from NICE the uptake of these new drugs has been slow. The effect of the new drugs can be affected by renal function, which is a major concern in the elderly. Another area where there is no evidence of the utility of the new anticoagulants is in patients with mechanical heart valves. These are two important patient cohorts requiring warfarin therapy we have termed ‘extreme phenotypes’. None of the current pharmacogenetic dosing algorithms have specifically focussed on elderly patients (over 75 years) with reduced renal function or patients with a mechanical heart valve who require a higher target INR (3.0-4.5).
The proposed study will be undertaken in the UK to develop two cohort-specific pharmacogenetic dosing algorithms. Cohort A will involve patients over 18 years with mechanical heart valves who require a target INR 3.0-4.5. Cohort B will involve patients over 75 years with reduced renal function (estimated Glomerular Filtration Rate <50ml/min) who are on warfarin for any other indication requiring a target INR 2-3. A single patient visit and blood sample will be required for DNA analysis.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
15/NW/0001
Date of REC Opinion
6 Mar 2015
REC opinion
Further Information Favourable Opinion