Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Having a stroke can affect a patient's ability to speak, eat, walk, work, care for themselves, and interact with others. Not only can it ruin one's life, but it can also be fatal. A stroke occurs when blood flow to the brain is blocked by a clot, depriving brain cells of oxygen. In people with atrial fibrillation, blood flow is sluggish in the top chambers of the heart, and blood clots can form there. When a piece of a clot breaks off, it can travel to the brain and cause a stroke. That's where blood thinners come in. Blood thinners, or anticoagulants, decrease the chances of blood clots forming in the heart, reducing the risk of stroke. Studies show that blood thinners are highly effective at reducing the risk of stroke by up to 95%.
The conventional blood thinner is warfarin, taken by mouth. Warfarin requires regular blood tests to make sure a patient getting the correct dose. The patient also may have to avoid certain foods since the medication can interact with them. Newer blood thinners, known as direct-oral anticoagulants (DOACs) are available, which do not require regular blood tests and do not interact with foods. Two of the new blood thinners are called rivaroxaban and apixaban. Like warfarin, they can be taken by mouth, and studies have shown them to be as effective as warfarin.
Both rivaroxaban and apixaban have been approved for stroke prevention in AF by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF and patient values around bleeding highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.
The trial is to assess bleeding rates and superiority of using apixaban versus rivaroxaban in patients with non-valvular atrial fibrillation.
Age ≥ 18 years old
Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines
Creatinine clearance =<15 ml/min calculated using the Cockcroft-Gault formula
active bleeding
history of mechanical valve
other indication for anticoagulation (e.g. mechanical valves, venous thrombosis)
Parallel
Apixaban
DrugRefer to Apixaban group
Rivaroxaban
DrugRefer to Rivaroxaban group
The rate of adjudicated clinically relevant bleeding (CRB) events
CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events
Adjudicated Major Bleeding events
Major Bleeding includes clinically overt bleeding and is associated with: * Fatal bleeding, and/or * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or * A fall in hemoglobin of ≥20 g/L, or * Leading to transfusion of ≥2 units of whole blood or red cells.
Adjudicated Clinically Relevant Non-Major Bleeding events
Clinically relevant non-major bleeding will be defined as: • Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: * Requiring medical intervention by a healthcare professional * Leading to hospitalization or increased level of care * Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation
Adjudicated stroke/TIA events
Stroke is defined as non-traumatic focal neurologic deficit lasting ≥ 24 hours and confirmed on cerebral imaging (computed tomography or magnetic resonance imaging). Transient ischemic attack (TIA) is defined as a temporary loss of blood flow to a part of the brain with focal neurologic deficit lasting \< 24 hours without imaging evidence of acute infarction. Strokes are to be classified as ischemic, hemorrhagic stroke, or uncertain. Hemorrhagic strokes are considered and will be reported as both bleeding events as well as stroke endpoints. The location of the bleeding can be determined from the diagnostic imaging reports.
All-cause mortality
Using a binary outcome of an event or no event (Individual rates of death, all causes).
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Ottawa Hospital Research Institute
Lead sponsor
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
Collaborator
Canadian Institutes of Health Research (CIHR)
Collaborator
