Non-valvular atrial fibrillation (NVAF) is a heart disorder, which affects the pumping of blood. This disturbance in blood flow can allow clots to form. These clots can cause blockages in blood vessels supplying the brain, resulting in stroke. NVAF patients are therefore often prescribed medicines that reduce blood clotting and lower the risk of stroke. However, these drugs can cause internal bleeding in the stomach and other organs. Internal bleeding can lead to disability and in the most severe cases, death. Prior medical research has shown that newer medicines may be just as effective as older treatments (warfarin) but might be less likely to cause serious bleeding. Research on the long term safety and effectiveness of these newer medications outside of a few medical studies is limited. This real world study is required in order to ensure that patients being prescribed these treatments in England are not placed at higher risk of bleeding or stroke in the long term, compared to using an older treatment. As well as investigating the safety of these medicines, we will investigate different approaches to estimating how long a patient is treated with warfarin, and see if this changes our findings regarding its safety and effectiveness.
Novel Oral Anticoagulants (NOACs) have at least equivalent effectiveness and improved safety in comparison to Vitamin K antagonists (VKA) such as warfarin in the clinical trial setting. It is important to ensure that the safety of patients treated with anticoagulation is also reflected in the long-term in the real-world setting. The primary aim of this study is to investigate the risk of bleeding in NVAF patients newly prescribed NOACs in England. An exploratory objective will be to investigate the effectiveness of NOACs in stroke prevention. A further exploratory objective will be to assess whether differing approaches to estimating days of supply of warfarin impact our findings on its comparative safety and effectiveness. We will use a retrospective cohort study design including patients with non-valvular atrial fibrillation (NVAF) who are newly prescribed NOACs in routine clinical practice in England. This study will utilise data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Propensity score matching will be used to create balanced treatment groups for pairwise comparisons, with warfarin serving as the reference group. Time from treatment to clinical events of interest will be summarised using Kaplan-Meier curves and modelled using Cox-regression analyses.
Major bleeding; Intracranial bleeding; Gastrointestinal bleeding; Clinically relevant non-major bleeding; Ischemic stroke; Ischemic stroke, unspecified stroke and systemic embolic events.
Robert Carroll - Chief Investigator - Bristol-Myers Squibb Pharmaceuticals Limited - UK ( BMS )
Cormac Sammon - Corresponding Applicant - PHMR Associates Limited ( UK )
Elaine Stamp - Collaborator - PHMR Associates Limited ( UK )
Megan Besford - Collaborator - PHMR Associates Limited ( UK )
Beth Nordstrom - Chief Investigator - Evidera, Inc
Sreeram Ramagopalan - Chief Investigator - London School Of Economics & Political Science
Robert Carroll - Corresponding Applicant - Bristol-Myers Squibb Pharmaceuticals Limited - UK ( BMS )
Robert Donaldson - Collaborator - Evidera Ltd - UK
Sophie Graham - Collaborator - Evidera, Inc
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation