Blood clots usually require treatment with blood thinners (anticoagulants). The clots often form in the veins and these may travel in the blood to the lungs. Blood clots can also form in the heart in atrial fibrillation, a condition that causes abnormal heart beats sometimes leading to small blood clots that travel in the blood vessels and get stuck in a smaller vessels such as those in the brain and cause a stroke.
Treatment with blood thinners is usually mandated for blood clots. The most commonly used blood thinners act by stopping a clotting factor (factor X (ten)) from thickening the blood. Because these blood thinners stop the blood from clotting normally, patients taking them can be at risk of severe and uncontrolled bleeding. The fear of major and uncontrolled bleeding from blood thinners could result in doctors avoiding blood thinners in patients who are likely to benefit from them.
We aim to estimate the risk of blood thinner-related severe bleeding and resulting complications. We also aim to estimate the healthcare resource use (this includes hospital stays, investigations, treatment and their costs) in patients with severe bleeding events depending on previous use of blood thinners.
This will help patients and clinicians to recognize who is at risk of bleeding and allow appropriate action to be taken, such as changing the risk factors and stopping blood thinners. This should help diminish the burden and cost of severe bleeding related to blood thinners.
This observational cohort study aims to (i) estimate the risk of major bleeding in patients treated with factor Xa inhibitors (FXai), and (ii) to estimate the risk of clinical outcomes and the healthcare resource utilization (HCRU) following major bleeding in FXai-treated patients and in patients without anticoagulant treatment. This study will utilise CPRD Aurum and linked HES, ONS and IMD data. The goal of this study is to support the safe and effective use of anticoagulants and the management of acute bleeds.
A cohort of patients with a first FXai prescription in therapeutic dose between January 2012 and October 2020 and a previous recording of a valid FXai indication will be defined. The outcome of interest will be major bleeding during the FXai treatment episode. Incidence rates of major bleeding will be calculated and risk factors for major bleeding on FXai will be identified by estimation of sub-distribution hazard ratios (SHRs) from multivariate Fine and Gray regression models accounting for the competing risk of mortality and adjusting for potential confounders.
FXai users with a major bleeding will also be followed after the bleeding event. The incidence of all-cause mortality, cardiovascular death, acute myocardial infarction, ischaemic stroke, acute kidney failure and acute liver failure up to 3 years after the major bleeding will be calculated. Risk factors for these clinical outcomes will be identified from multivariate Fine and Gray regression models. For the fatal outcomes Cox regression will be used. In addition, all HCRU and their related costs in the 3 years following the major bleeding will be determined. Furthermore, a cohort of patients with a major bleeding event without a previous anticoagulant recording will be defined and the same analyses as for the FXai users with a major bleeding event will be performed in this patient group.
Major bleeding; clinical outcomes following major bleeding (death from any cause, cardiovascular death, acute myocardial infarction, ischaemic stroke, acute kidney failure and acute liver failure); healthcare resource utilization following major bleeding.
He Gao - Chief Investigator - AstraZeneca Ltd - UK Headquarters
Carlos Martinez - Corresponding Applicant - Institute for Epidemiology, Statistics and Informatics GmbH (Pharma Epi)
Alexander Cohen - Collaborator - King's College London (KCL)
Chaozer Er - Collaborator - National University of Singapore
Christopher Wallenhorst - Collaborator - Institute for Epidemiology, Statistics and Informatics GmbH (Pharma Epi)
Jil Billy Mamza - Collaborator - AstraZeneca Ltd - UK Headquarters
Kamran Hussain - Collaborator - AstraZeneca Ltd - UK Headquarters
Nikki Stamp - Collaborator - AstraZeneca Ltd - UK Headquarters
Ruiqi Zhang - Collaborator - AstraZeneca Ltd - UK Headquarters
Satarupa Choudhuri - Collaborator - NHS England
Alexander Cohen - Collaborator - King's College London (KCL)
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation