Understanding the use, benefit and harms of directly acting oral anticoagulants over the COVID-19 period: Protocol for National Health Service England Secure Data Environment study

<ns3:p>Individuals with atrial fibrillation (AF) are at increased risk of thromboembolic stroke due to blood stasis in the left atrium, which can lead to clot formation. Warfarin is effective in preventing stroke in these individuals but is associated with an increased risk of bleeding and requires frequent monitoring to maintain therapeutic control. Direct oral anticoagulants (DOACs) were developed to address some of these limitations and have been shown to be as effective as warfarin for stroke prevention, with a lower risk of bleeding complications and reduced need for monitoring. However, direct comparisons between individual DOACs in routine clinical practice remain limited. Here, we provide a protocol for a study aims to estimate the comparative effectiveness and safety of apixaban, edoxaban and rivaroxaban in individuals with AF. The study will emulate a hypothetical randomised controlled trial using routinely collected healthcare data from multiple sources, including primary care records, secondary care data, mortality records and drug dispensing data, covering the period from 1 November 2019 to 31 December 2024. The study population will include adults aged 18 years and over with AF who were dispensed apixaban, edoxaban or rivaroxaban. The primary effectiveness outcome will be ischaemic stroke and the primary safety outcome will be major bleeding events. The findings from this study will provide real-world evidence to inform clinical decision-making and support the optimal use of DOACs for stroke prevention in individuals with AF.</ns3:p>