Current RCT methodology often leads to recruitment of highly selected participants with less diversity than the clinical population, and challenges with enrolment and retention of patients. New RCT approaches are needed that can realise the value of the world-leading data quality and infrastructure of the NHS. AF is the most common heart rhythm abnormality, expected to double in prevalence in the next few decades, and leads to a considerable burden for patients and society at-large.  In particular, the impact of stroke, cognitive decline and vascular dementia are all major public health concerns.

DaRe2THINK will test the hypothesis that DOACs are effective and cost-effective in patients with AF at low or intermediate risk of stroke by using an ambitious and innovative data-enabled approach through the Clinical Practice Research Datalink (CPRD) in Primary Care General Practices across England.

Exclusion Criteria (Continued):

• Prior major bleeding requiring hospitalisation in the last 3 years.
• Condition that poses a significant risk for bleeding (within 12 months) including gastrointestinal ulceration, brain/spinal/ophthalmic injury or surgery, arteriovenous malformations or vascular aneurysms, major intraspinal or intracerebral vascular abnormalities, hepatic disease associated with coagulopathy, known or suspected oesophageal varices, and cancers with high bleeding risk.
• Estimated glomerular filtration rate <30 mL/min/1.73m2 measured within the last 12 months.
  Patients receiving systemic treatment with azole-antimycotics within the last 3 months (ketoconazole, itraconazole, voriconazole and posaconazole).
• Documented diagnosis of dementia.
• Hypersensitivity or known intolerance to direct oral anticoagulants