Although large clinical 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 the drug to. Real-world data, as collected in the Clinical Practice Research Database, can offer valuable insight into the benefits and risks of new drugs used outside of a well-controlled clinical trial setting. Direct Oral Anticoagulants (DOACs) are a new type of blood thinners that prevent the occurrence of blood clots. An important side effect of these medicines is the risk of bleeding. Although we do have information from the clinical trials about the benefits and risks, more research is needed to determine the benefit-risk balance of these medicines in a real-world setting. Additionally, it is still unclear if the benefit- risk balance would be different for specific subgroups, such as patients with an impaired kidney function or with an older age. With the current study we would like to understand the prescribing and use of DOACs in a real-world setting as well as assessing the risk of major bleeding in DOAC users to further establish the benefit-risk balance.
Since the introduction of the direct oral anticoagulants (DOACs) there are still some uncertainties around the effectiveness and safety compared to vitamin K antagonists (VKAs), especially with the respect to bleeding within specific subgroups. This study is undertaken to 1) assess the safety of the DOACs compared to VKAs in (subgroups of) patients with non-valvular atrial fibrillation (NVAF) in a real-world setting, 2) describe the utilization of DOACs in the EU for treatment of NVAF, and 3) describe prescribers' compliance with recommendations made in the summary of product characteristic for each DOAC. Methods The base population will consist of all (D)OAC users between 2008-2015. Three studies will be conducted to answer the research questions listed under objectives. One retrospective cohort study (objective 1) and two descriptive studies (objective 2&3). For the descriptive studies number of patients and percentages will be reported. Baseline characteristics will be summarized as means and standard deviations or proportions where appropriate. Crude incidence rates of outcomes per 1,000 person years will be estimated, stratified by sex and age groups. Cox proportional hazard regression analysis will be applied to estimate bleeding risk (adjusted hazard ratios, HR) of (D)OAC treatment.
Incidence of major bleeding; Duration of use; Persistence; Switching; Drug-interactions.
Helga Gardarsdottir - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Hendrika van den Ham - Collaborator - Utrecht University
Olaf Klungel - Collaborator - Utrecht University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation