Stroke Prevention in Atrial Fibrillation: A Clinical Perspective on Trials of the Novel Oral Anticoagulants

Atrial fibrillation (AF) is a common heart rhythm disturbance; its incidence increases with age, and it is also an independent risk factor for stroke. Anticoagulation has been proven as the most effective way to reduce the risk of stroke in patients with AF, and vitamin K antagonists have been used for decades as the gold standard treatment. Vitamin K antagonists have a narrow therapeutic window in addition to variable pharmacokinetics and pharmacodynamics, and they frequently interact with food and other drugs, requiring coagulation monitoring to ensure balance between safety and efficacy. The novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban selectively target either thrombin or Factor Xa and have predictable pharmacologic profiles, removing the need for routine coagulation monitoring. This article summarizes phase III data in patient subtypes and discusses controversies surrounding AF management with these agents. Results indicate that NOACs in non-valvular AF have an overall improved efficacy–safety profile compared with warfarin. Significantly fewer fatal bleeding events were observed in patients randomized to rivaroxaban, apixaban, or edoxaban compared with those on warfarin, and significant reductions in the incidence of life-threatening bleeding were observed in patients randomized to dabigatran. All four pivotal trials testing the NOACs against warfarin showed significantly lower rates of intracranial bleeding in patients administered NOACs. These results suggest that wider use of NOACs has the potential to improve outcomes for most patients with AF.