New frontiers for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia, affects over 2.5 million people in the USA and is responsible for one fifth of the 700,000 ischemic strokes per year. For the last 50 years, long-term anticoagulation with warfarin has been the most effective therapy for preventing stroke in patients with AF and other risk factors. However, many AF patients are poor candidates for this treatment, and management of the drug can be challenging. Such challenges include the need for frequent monitoring, interactions with food and other medications, variability in metabolism and a delayed onset of action. Antiplatelet therapy has also been evaluated, and though it is not as effective at preventing ischemic strokes, it may provide some benefit for patients who cannot tolerate warfarin. Recent clinical trials have tested pharmacologic alternatives to warfarin, and new treatment options have emerged. Of these alternatives, the direct oral thrombin inhibitor dabigatran and the oral factor Xa inhibitor rivaroxaban, which have minimal interactions and require no INR monitoring, have already been approved by the FDA. The field may soon be further expanded as the oral factor Xa inhibitor apixaban has shown promise in its recent phase 3 trial and is under consideration for FDA approval. Nonpharmacologic approaches to stroke prevention in AF are under development as well. These approaches focus on occlusion or ligation of the left atrial appendage, which is frequently the location of thrombus formation. While such procedures have been done often during other cardiac surgeries, newer methods have focused on percutaneous techniques, including ones that may not require anticoagulation afterwards. In addition, new diagnostic modalities may detect paroxysmal AF with more sensitivity, potentially expanding the population to be treated and the potential impact of stroke preventive strategies on the population. This review provides a practical guide to current treatment and diagnostic options and focuses on emerging therapies.