Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation

Approximately 250,000 Canadians are affected by atrial fibrillation (AF). Stroke is a complication of AF, and Canadians with AF are five times more likely to have a stroke and are twice as likely to die than individuals without AF. AF and stroke are more common among the elderly. Preventing thromboembolic events such as stroke is an important part of managing AF patients. Antithrombotic strategies for AF patients include anticoagulant drugs, notably the coumadin class of vitamin K antagonists (VKAs), such as warfarin, and antiplatelet agents, such as aspirin. VKAs reduce the risk of stroke in patients with AF by more than 60% when compared with no treatment, and by 30% to 40% when compared with low-dose aspirin. However, VKA use is associated with some drawbacks, including a need for laboratory monitoring, an increased risk of bleeding complications, and several food and drug interactions. An improved understanding of how the blood clotting cascade works has led to the development of new oral anticoagulants (NOACs) that exhibit more predictable pharmacokinetics and pharmacodynamics, thereby obviating the need for laboratory monitoring. The NOACs that have either been approved, or are under review by regulators, for the prevention of thromboembolic events in AF patients include dabigatran, a direct thrombin inhibitor, and the direct Factor Xa (FXa) inhibitors, rivaroxaban, apixaban, and edoxaban. Ximelagatran, a direct thrombin inhibitor, was the first NOAC to be approved for use, but was withdrawn from the market in 2006 because of safety concerns. While dabigatran, apixaban, and rivaroxaban have been demonstrated to be effective in preventing stroke/systemic embolism (SE) in AF patients, the relative effectiveness and associated bleeding risks of these NOACs, both among themselves and in comparison to warfarin, is not clear. Therefore, the aim of this project was to systematically review and analyze the safety and effectiveness of three NOACs – namely dabigatran, rivaroxaban, and apixaban – compared with warfarin in patients with non-valvular AF. In addition, the cost-effectiveness of the NOACs and warfarin was assessed using economic modelling.