Atrial Fibrillation (AF) is a heart condition in which patients have an irregular heartbeat. Patients with AF are at a higher risk of stroke and may be prescribed a type of medication called anticoagulants to reduce the risk of stroke.
Treatment guidelines for anticoagulants are based on the results of randomised clinical trials which have very strict entry criteria. This means that many people with AF who are prescribed these drugs by their GP could be quite different to patients studied in clinical trials. The types of patients who are usually not allowed to take part in clinical trials include people with existing medical conditions, people with no other stroke risk factors, and pregnant patients. Patients included in anticoagulant clinical trials may therefore not be representative of the patients who are prescribed these drugs in clinical practice.
In this study we will look at how well a specific anticoagulant medicine called apixaban works compared with another treatment called warfarin in people who would have been excluded from a landmark anticoagulant trial (the ARISTOTLE trial), in order to help improve treatment guidelines for these people. We will use information routinely collected by GPs and hospitals to assess the impact of apixaban and warfarin in preventing stroke and blood vessel blockage. First we will see how well these treatments work when prescribed to people that are similar to those included in the ARISTOTLE trial. Then we will see how well the treatments work when prescribed to patient groups excluded from this trial.
Patients with atrial fibrillation (AF) are at a greatly increased risk of stroke; prophylactic treatment with anticoagulation medication reduces this risk. In the last decade several direct oral anticoagulants (DOACs) have been approved providing an alternative to the standard treatment warfarin which has many drug and dietary interactions and requires onerous monitoring. Treatment guidelines for AF patients are based on the results from randomised controlled trials (RCT).
There is increasing interest in the effectiveness of medications in routine clinical practice to confirm trial results and estimate drug effectiveness in patient groups excluded from or underrepresented in clinical trials. There is however some uncertainty about the suitability of using non-interventional data to address questions about drug effectiveness and on the most suitable methods to be used. The aims of this study are to attempt to measure the association between anticoagulation treatments for stroke prevention in AF using electronic health records (EHRs) and to develop a methodological framework for using observational EHRs to answer questions about DOACs among patients excluded from or underrepresented in the RCTs.
This study will use individual patient data from ARISTOTLE1, a pivotal trial conducted 2006-2011 in 18,201 patients that demonstrated superiority of the DOAC apixaban compared with warfarin in prevention of stroke. The individual patient data will be used to match to UK NHS patients with anonymised routinely-collected EHRs from CPRD. Analysis of drug effectiveness in this cohort will help determine whether EHR data are suitable for this kind of research question. Selecting EHR patients similar to trial patients will remove much of the variability in baseline risk of the study outcomes between trial participants and EHR patients. If we can demonstrate replication of trial results in our ARISTOTLE-analogous cohort, the same methodology will be used to determine drug effectiveness in patient groups underrepresented in the trial.
Time to event: stroke, systemic embolism, myocardial infarction, all-cause death, major bleeding
Kevin Wing - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Emma Powell - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Anna Schultze - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Turki Bin Hammad - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Usha Gungabissoon - Collaborator - GSK
Yan-Ling Lu - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation