Atrial fibrillation (AF) is a common type of supraventricular tachyarrhythmia. While a supraventricular tachyarrhythmia is a tachycardic rhythm originating above the ventricular tissue, AF is characterized by uncoordinated atrial activation with consequent deterioration of mechanical function. AF is the most common cardiac arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. The estimated prevalence of AF is 0.4% to1 % in the general adult population, occurring in about 2.2 million people in the U.S. The prevalence increases to about 6 % in people age 65 or older and to 10% in people age 80 or older. The burden of AF in the U.S. is increasing. It is estimated that by the year 2050 there will be 12.1 million Americans with AF, representing more than a twofold (240%) increase since 2000. However, this estimate assumes no further increase in the age-adjusted incidence of AF beyond 2000. If the incidence of AF increases at the same pace, then the projected number of adults with AF would be 15.9 million, a threefold increase from 2000. Although generally not as immediately life threatening as ventricular arrhythmias, AF is associated with significant morbidity and mortality. Patients with AF have increased risk of embolic stroke, heart failure, and cognitive impairment; reduced quality of life; and higher overall mortality. Patients with AF have a fivefold increased risk of stroke, and it is estimated that up to 25% of all strokes in the elderly are a consequence of AF.4 Furthermore, AF-related strokes are more severe, with patients twice as likely to be bedridden as patients with stroke from other etiologies, and are also more likely to result in death. Consistent with the nature of these events, AF-related stroke constitutes a significant economic burden, costing Medicare approximately $8 billion annually. Management of AF involves three distinct areas: rate control, rhythm control, and prevention of thromboembolic events. Strategies for preventing thromboembolic events can be categorized into (1) optimal risk stratification of patients and (2) prophylactic treatment of patients identified as being at risk. The KQs considered are as follows: KQ1: In patients with nonvalvular atrial fibrillation, what are the comparative diagnostic accuracy and impact on clinical decisionmaking (diagnostic thinking, therapeutic, and patient outcome efficacy) of available clinical and imaging tools for predicting thromboembolic risk? KQ2: In patients with nonvalvular atrial fibrillation, what are the comparative diagnostic accuracy and impact on clinical decisionmaking (diagnostic thinking, therapeutic, and patient outcome efficacy) of clinical tools and associated risk factors for predicting bleeding events? KQ3: What are the comparative safety and effectiveness of specific anticoagulation therapies, antiplatelet therapies, and procedural interventions for preventing thromboembolic events: a. In patients with nonvalvular atrial fibrillation? b. In specific subpopulations of patients with nonvalvular atrial fibrillation? KQ4: What are the comparative safety and effectiveness of available strategies for anticoagulation in patients with nonvalvular atrial fibrillation who are undergoing invasive procedures? KQ5: What are the comparative safety and effectiveness of available strategies for switching between warfarin and other, novel oral anticoagulants in patients with nonvalvular atrial fibrillation? KQ6: What are the comparative safety and effectiveness of available strategies for resuming anticoagulation therapy or performing a procedural intervention as a stroke prevention strategy following a hemorrhagic event (stroke, major bleed, or minor bleed) in patients with nonvalvular atrial fibrillation?