Atrial fibrillation (AF) is the most common arrhythmia encountered by generalists and cardiologists alike. Much of the attendant morbidity from AF arises from systemic embolic complications which are effectively reduced with utilization of anti-platelet and/or anticoagulant therapy. The systemic embolic complications of AF and the medical therapy to attenuate these risks are very well established. Through the course of this review, we aim to highlight the complex relationship between AF and other, “non-embolic” outcomes. The presence of AF has been demonstrated to be associated with a 1.5 to 2-fold increase in mortality across numerous observational cohorts. Still further, AF frequently coexists with heart failure, whether as a causative factor or a consequence of underlying structural heart disease or neurohumoral derangement, where its presence is associated with worse clinical outcomes. Whether AF is an independent risk factor for acute coronary syndromes (ACS) remains controversial, though its occurrence in patients with ACS has been shown to be associated with adverse outcomes both in observational cohorts as well as clinical trial populations. Individuals with AF have a 1.5 to 3-fold increase in the rate of hospitalization and are at elevated risk for other arrhythmic disorders including both bradyarrhythmias as well as tachyarrhythmias. AF leads to considerable morbidity and mortality for patients and exacts a tremendous financial toll on the healthcare system—estimated to range from $6.0 to $26.0 billion. Given the current demographic transition in developed countries, the prevalence of AF will continue to increase and the need for refined approaches to risk stratification and pharmacotherapeutic interventions to attenuate the burden on patients will only become more important.

N.R. Desai and R.P. Giugliano received an honorarium through an educational grant from Sanofi Aventis for their time and expertise spent writing this article. R.P. Giugliano has also received research grant support and honoraria for CME lectures/consulting services from Daiichi-Sankyo, Merck. He has also received honoraria for CME lectures from Bristol Myers Squibb.