Although large trials are carried out before registration of a new drug, the patients included in such trials are carefully selected and not necessarily representative for the patients that doctors initially prescribe it to.
Real-world data can offer valuable insight into the safety and effectiveness of new drugs used outside of a well-controlled clinical trial setting.
Patients with Atrial fibrillation (AF) are at increased risk of stroke. Warfarin or NOACs (Novel
Oral Anticoagulants) are prescribed to prevent stroke, and are associated with bleeding
complications. In addition, patients with diabetes are at increased risk for both stroke and
bleeding.
With this study we would like to estimate the risk of major bleeding and stroke in patients with AF and diabetes who are users of NOAC compared to warfarin in a real-world setting, to help establish the effectiveness of existing and future risk minimization measures.
Atrial fibrillation (AF) is associated with a five-fold risk of stroke. Type 2 diabetes (T2DM) is one of the most common comorbidities in AF patients, and a well-known risk factor for stroke. Additionally, T2DM patients have high prevalence of comorbidities predisposing to bleeding.
Objective: With this study we aim to compare the risk of stroke and major bleeding associated with NOACs compared to warfarin in patients with NVAF and T2DM in the Clinical Practice Research Datalink (CPRD)
Methods: A retrospective cohort study using the UK CPRD. Participants are patients with a registered diagnosis of AF and T2DM, who are 1-year naïve users of NOACs or Warfarin, followed from the date of first prescription until the end of follow-up period, death, discontinuation of treatment for more than 180 days, switching or an
outcome of interest, whichever came first.
Outcomes: HRs of stroke (ischaemic, non-specified and haemorrhagic stroke), myocardial
infarction, and major bleeding (gastrointestinal (GI), intracranial, and bleeding on other sites).
Statistical analysis: The number and percentage of users with comorbidity or concomitant medication at baseline will be calculated, as well as the crude incidence rates of outcomes within 1 year per 100 person-years. Cox proportional hazard regression analysis will be performed to estimate the HR adjusted for a history of comorbidities and drug use. The effect of continuous treatment will be considered in the analysis by taking discontinuation and switching events into account.
HRs of stroke (ischaemic, non-specified and haemorrhagic stroke), myocardial infarction, major bleeding (gastrointestinal (GI), intracranial, and bleeding on other sites).
Anthonius de Boer - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Fatima Rüstem Güllüoglu - Collaborator - Utrecht Institute for Pharmaceutical Sciences
Hendrika van den Ham - Collaborator - Utrecht University
Joris Komen - Collaborator - Utrecht Institute for Pharmaceutical Sciences