Anticoagulants otherwise known as 'blood thinning' agents are classes of drugs used for treating and preventing blood clots and stroke in patients with previous history of irregular heartbeats. Warfarin is the most popular drug for treating blood clots and preventing strokes. However, patients on warfarin require regular blood tests in addition to other side effects such as bleeding and vomiting which may result in hospitalisation. New anticoagulants (Dabigatran, Rivaroxaban, Apixaban and Edoxaban) that do not require regular blood tests with fewer side effects are now on the market. The marketing authorisation for each new anticoagulant differs and so also the reason for their prescription largely based on the result of clinical trials. Clinical trials however are conducted in patients that may be different from real-world settings. Real-world data studies are crucial to our understanding of the use of new anticoagulants outside clinical trials. The risk profile of patients given the new anticoagulants may have changed over time. The aim of this study is to utilise routinely collected primary care data to study how the use of the new anticoagulants have evolved over time and the characteristics of patients prescribed these drugs.
Warfarin is the mainstay of therapy to reduce thromboembolic stroke risk in patients with non-valvular atrial fibrillation (NVAF). Major limitations associated with the use of warfarin include; a narrow therapeutic window, regular monitoring requirement, multiple drug and food interactions and the risk of haemorrhage. Warfarin alternatives, New oral anticoagulants (NOACs; Dabigatran, Rivaroxaban, Apixaban and Edoxaban) are simpler to dose and do not require therapeutic monitoring. The marketing authorisations for each NOAC are subtlety different creating potential channelling biases which largely remain unaddressed. Clinicians require comparative data to make informed oral anticoagulant prescribing decisions. Real-world data studies are crucial to our understanding of OACs utilisation outside clinical trials. Clinical trial populations may not be universally representative of the general population who are prescribed OACs in routine clinical practice. In addition, the risk profile of patients given NOACs to warfarin may have changed over time. The aim of this study is to utilise real-world data available from the Clinical Practice Research Datalink (CPRD) to gain detail insight on the evolution of baseline characteristics of anticoagulated patients with atrial fibrillation, prescribed different OACs for the first time.
For the purpose of this analysis, the date of anticoagulation treatment initiation in the study period will determine exposure cohorts. The first prescription date for the following OACs: dabigatran, rivaroxaban, apixaban, edoxaban and warfarin will be considered as the index for assessing the baseline characteristics. For patients with multiple distinct period of exposure to any one of the OACs only the baseline characteristics at the first distinct period will be assessed. Covariates Demographic variables: Sex, age, ethnicity, year of AF diagnosis, time since diagnosis; Clinical variables: Body mass index (BMI), smoking history, alcohol consumption; Comorbidities include: congestive heart failure, hypertension, type II diabetes mellitus, vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), history of stroke/TIA/TE, history of major bleeding, chronic liver disease and chronic kidney disease (including most recent creatinine clearance); CHA2DS2-VASc, HAS-BLED and SAMe-TT2R2S scores In addition history of cardioversion and dyspepsia symptoms will be considered as comorbidities of interest, utilisation of acetylsalicylic acid (ASA), beta-blockers, amiodarone and verapamil.
Michael Marcus - Chief Investigator - University of Liverpool
Michael Marcus - Corresponding Applicant - University of Liverpool
Chris D Poole - Collaborator - Digital Health Labs Limited
Gregory Y H Lip - Collaborator - University of Birmingham
Naj Rotheram - Collaborator - Boehringer-Ingelheim - UK