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Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults with a current prevalence estimated at 1.5% to 2% of the general population. With the aging population in the United States, AF prevalence is projected to increase steadily from approximately 6 million cases in 2010 to 15.9 million by 2050.1 AF is a major cause of stroke, being responsible for 15% of all strokes and 30% of strokes in patients over age 80.2 Unfortunately, stroke is the leading cause of long-term disability and the fourth leading cause of death in the United States.3,4 The presence of AF is associated with a 4- to 5-fold risk of ischemic stroke,5 and the incidence increases significantly with advancing age. Moreover, strokes associated with AF are more severe; AF-related stroke victims have a 50% greater likelihood of becoming disabled or handicapped and a >50% likelihood of death.6,7 Accordingly, stroke prevention with anticoagulation is one of the main pillars of AF management, and guidelines for anticoagulation have become more stringent recently. The Canadian Cardiovascular Society had lowered their threshold for recommending oral anticoagulation (OAC) for CHADS2 (congestive heart failure, hypertension, age 75 years, diabetes mellitus, stroke) score ≥1, the European Society of Cardiology (ESC) for CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) score ≥1, and the American College of Cardiology (ACC) for CHA2DS2-VASc score ≥2.1,8-10

Anticoagulation for AF and Limitations

Several randomized placebo-controlled trials have demonstrated that OAC is highly effective in preventing thromboembolism with AF, and landmark meta-analysis with warfarin demonstrated a 64% relative stroke reduction and 26% relative mortality reduction.11,12 Although OAC is the current gold standard for AF stroke prevention, a significant proportion (30%-50%) of eligible patients do not receive therapy due to absolute contraindications or perceived risks of bleeding.13,14 Furthermore, OAC increases the incidence of major bleeding despite the use of novel OAC (NOAC); a recent meta-analysis of all 4 NOAC trials showed major bleeding rates of 6.2% with warfarin and 5.3% with NOAC.15 Even though the risk of intracranial hemorrhage is consistently lower with NOAC, overall major bleeding is not diminished with dabigatran or rivaroxaban compared with warfarin.16,17 Apixaban and edoxaban were the only 2 agents that lowered major bleeding compared to warfarin.18,19

There are also other concerns with OAC therapy, including patients with renal and liver dysfunction (excluding use with NOAC), high risk of falls, noncompliance, and patients requiring dual antiplatelet therapy after stent placement. For warfarin, there are additional issues with drug and diet interaction, the need for anticoagulation monitoring, and narrow therapeutic window, with time in therapeutic range of only 50% to 60% in community practices.20,21...

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