Atrial fibrillation (AF) is defined in the most recent combined American College of Cardiology (ACC) / American Heart Association (AHA) / European Society of Cardiology (ESC) clinical guidelines as “a supraventricular tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of mechanical function.”1 It is the most common sustained cardiac arrhythmia encountered in clinical practice.1,2 Up to 1% of the general population experiences AF.1 The prevalence is highly age-dependent, with an 8% prevalence among patients aged ≥80 years. AF is more common in men than in women (1.1% versus 0.8%; P<.001).3 Risk factors for AF include thromboembolism, hypertension, valvular heart disease, and heart failure.1,2 At the same time, AF contributes significantly to patient morbidity and mortality; it is estimated that up to 15% of all strokes are caused by underlying AF.2 References: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2006;48:854-906. Roy D, Kerr CR. Canadian Cardiovascular Society Consensus Conference 2004: Atrial Fibrillation. Available at: http://www.ccs.ca/download/ consensus_conference/consensus_conference_archives/2004_Atrial_Fib_full.pdf. Accessed March 4, 2010. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults – national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370-2375.

In this analysis by Humphries et al, International Classification of Diseases (ninth revision) codes for admissions to acute care hospitals in Canada were used to estimate the prevalence of hospitalization for AF between 1997/1998 and 1999/2000, and subsequent readmissions for stroke in all 10 provinces and overall in Canada. The results showed that the rate of hospitalization with AF is increasing in Canada and contributes significantly to healthcare costs. Reference: 1. Humphries KH et al. Population rates of hospitalization for atrial fibrillation/flutter in Canada. Can J Cardiol. 2004;20:869-876.

AF can worsen pre-existing heart failure (HF) and can rarely lead on its own to HF. According to Maisel and Stevenson, the prevalence of AF in HF increases from <10% in patients with New York Heart Association functional class I to 50% in functional class IV. Furthermore, these 2 disorders share common risk factors and cardiovascular effects. Reference: 1. Maisel WH, Stevenson LW. Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol. 2003;91(suppl):2D-8D. 3

AF is associated with a great variability in presentation AF is associated with a great variability in presentation. The most common presenting symptoms include lightheadedness, palpitations, syncope, dyspnea, fatigue, and chest pain.1 However, AF may be asymptomatic in as many as one-third of patients.2 Page et al determined that asymptomatic episodes are up to 12 times more frequent than symptomatic episodes.3 Furthermore, previously symptomatic AF may become asymptomatic over time, particularly among elderly patients.1 References: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2006;48:854-906. Savelieva I, Camm AJ. Silent atrial fibrillation – another Pandora's box. Pacing Clin Electrophysiol. 2000;23:145-148. Page RL, Tilsch TW, Connolly SJ, et al; Azimilide Supraventricular Arrhythmia Program (ASAP) Investigators. Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide. Circulation. 2003;107(8):1141-1145.

The CHADS2 score system was designed to simplify the determination of stroke risk in general practice. This scheme amalgamates the individual risk factors: congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack (TIA). The first 4 risk factors are assigned 1 point each, and prior stroke/TIA is allotted 2 points (hence, the subscript "2"). Using this system, the stroke rate per 100 patient-years without antithrombotic therapy is expected to increase by a factor of 1.5 for each 1-point increase, from 1.9 for a score of 0, to 18.2 for the highest score of 6. Reference: 1. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864-2870.

The ACC/AHA/ESC guidelines outline 3 management objectives: rate control, prevention of thromboembolism, and correction of the rhythm disturbance. The authors add that these are not mutually exclusive goals.1 Several recent authors have stressed the importance of expanding the scope of management to greater reductions in cardiovascular (CV) morbidity and mortality.2-5 References: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2006;48:854-906. Singh SN, Tang XC, Singh BN, et al; SAFE-T Investigators. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy. J Am Coll Cardiol. 2006;48:721-730. Hohnloser SH, Crijns HJ, van Eickels M, et al; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678. Prystowsky EN. Assessment of rhythm and rate control in patients with atrial fibrillation. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10. Camm AJ, Reiffel JA. Defining endpoints in clinical trials on atrial fibrillation. European Heart Journal Supplements. 2008;10(suppl. H):H55-H78. 6

Data from recent trials – notably the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM),1 where “better” rate control did not result in superior outcomes – support the perspective that the therapeutic goals for AF could be re-examined, and the traditional goal of reducing AF burden could be supplemented by an emphasis on the reduction of CV morbidity, hospitalizations, and prevention of thromboembolism, as well as careful attention to mortality outcomes in AF. This “new paradigm” in AF care would then evolve from the concept of “rate versus rhythm control” to a concept of “symptom and disease control,” emphasizing patient well-being, and de-emphasizing electrocardiographic recurrences of AF, particularly if these are associated with minimal or no symptoms. Reference: Cooper HA, Bloomfield DA, Bush DE, et al; AFFIRM Investigators. Relation between achieved heart rate and outcomes in patients with atrial fibrillation (from the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] Study). Am J Cardiol. 2004;93(10):1247-1253.

This slide provides a comparison of the benefits and risks of the approved (as of 2008) antiarrhythmic drugs.1 Since this analysis by Savelieva and Camm was published in 2008, Health Canada has approved the use of dronedarone for the treatment of AF to reduce the risk of AF-related CV hospitalization.2 Health Canada approval was based on the results of ATHENA (A Placebo-Controlled, Double-Blind, Parallel-Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter).3 References: Savelieva I, Camm J. Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches. Europace. 2008;10:647-665. Sanofi-aventis Canada Inc. Multaq™ (dronedarone) product monograph. July 31, 2009. Hohnloser SH, Crijns HJ, van Eickels M, et al; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.

In ATHENA, 4600 patients with paroxysmal or persistent AF or flutter and risk factors for vascular and stroke events were randomized to dronedarone or placebo. Compared with placebo, dronedarone decreased the incidence of CV hospitalization or death (primary outcome) by 24% (31.9% incidence in dronedarone group versus 39.4% in control group; hazard ratio [HR] 0.76; 95% confidence interval [CI], 0.69 to 0.84; P<0.001). CV deaths and deaths due to cardiac arrhythmia were also significantly reduced with dronedarone use (HR 0.71; P=0.03 for CV death and HR 0.55; P=0.01 for arrhythmia death). Reference: Hohnloser SH, Crijns HJ, van Eickels M, et al; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.

Warfarin is the current gold standard for the prevention of stroke in AF patients; however, it is associated with a number of significant limitations, most notably bleeding, but also including a slow onset of action, significant genetic variation in patient response, drug resistance, and multiple food and drug interactions.1 A number of new antithrombotic strategies are under active investigation as potential alternatives to warfarin to prevent AF-related stroke. The Randomized Evaluation of Long-term anticoagulation therapY (RE-LY)2 compared the benefit of dabigatran to warfarin in 18,113 AF patients who had an elevated risk of stroke. Though designed as a noninferiority trial, dabigatran 150 mg bid was found to be significantly superior to warfarin in the prevention of stroke or systemic embolism (1.11% versus 1.69%; relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001). The annual rate of major bleeding was 3.36% in the warfarin group, as compared with 3.11% in the high-dose (150 mg) dabigatran group (P=0.31) and 2.71% in the low-dose (110 mg) group (P=0.003). References: Lin PJ. Reviewing the reality: why we need to change. Eur Heart J Suppl. 2005;7(suppl E):E15-E20. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.

The treatment of AF in the emergency room (ER) is somewhat controversial, since there are no large randomized, controlled trials to help the clinician decide on the preferred strategy. This slide indicates some of the essential aspects of AF management in the ER. In the absence of specific directed guidelines, clinicians must carefully assess the potential causes of the AF, identify the underlying heart disease, and pay special attention to controlling symptoms and preventing stroke, as well as arranging for timely follow-up with respect to long-term management of the arrhythmia.