1. 1 Clinical Overview of Atrial Fibrillation Edward L.C. Pritchett, M.D. Consulting Professor of Medicine Divisions of Cardiology and Clinical Pharmacology Duke University Medical Center Durham, North Carolina

2. 2 Atrial Fibrillation Prevalence Most common sustained cardiac arrhythmia 1Most common sustained cardiac arrhythmia 1 Most common diagnosis for arrhythmia-related hospitalization 2Most common diagnosis for arrhythmia-related hospitalization 2 Estimated >2.3 million US adults have AF 3Estimated >2.3 million US adults have AF 3 Prevalence of AF increases with age and with an aging population 4Prevalence of AF increases with age and with an aging population 4 1 Bialy D et al. J Am Coll Cardiol 1992; 19-41A. 2 Fuster V et al. Circulation 2006; 114:e257-e354 3 Go AS et al. JAMA 2001; 285:2370-2375. 4 Chug SS et al. J Am Coll Cardiol 2001: 37:371-378

3. 3 Clinical Presentation of Atrial Fibrillation Atrial fibrillation is most commonly identified because patients have symptoms 1Atrial fibrillation is most commonly identified because patients have symptoms 1 The most appropriate use of antiarrhythmic drugs in patients with atrial fibrillation is for relief of symptoms 2,3The most appropriate use of antiarrhythmic drugs in patients with atrial fibrillation is for relief of symptoms 2,3 Symptoms closely associated with occurrence of atrial fibrillation are palpitations, dyspnea, chest pain, dizziness, asthenia, fatigue, nervousness, increased sweating 4Symptoms closely associated with occurrence of atrial fibrillation are palpitations, dyspnea, chest pain, dizziness, asthenia, fatigue, nervousness, increased sweating 4 1 Psaty BM et al. Circulation 1997;96:2455-2461. 2 Page RL. N Eng J Med 2004;351:2408-2416 3 Fuster V et al. Circulation 2006;114:e257-e354. 4 Bhandari AK et al. Am Heart J 1992;124:381-386.

4. 4 Symptomatic Arrhythmias as an Outcome in Antiarrhythmic Drug Approvals for Atrial Fibrillation and Other Supraventricular Arrhythmias 1986 verapamil PO IR - PSVT1986 verapamil PO IR - PSVT 1991 flecainide PO - PSVT, AF1991 flecainide PO - PSVT, AF 1996 ibutilide IV - AF1996 ibutilide IV - AF 1997 propafenone PO IR - PSVT, AF1997 propafenone PO IR - PSVT, AF 1999 dofetilide PO - AF1999 dofetilide PO - AF 2000 d,l sotalol PO - AF2000 d,l sotalol PO - AF 2003 propafenone SR PO - AF2003 propafenone SR PO - AF Pritchett E, PACE, 1998;21:1457-1469.

5. 5 Limitations of Current Therapies Pharmacological Conversion with IV Antiarrhythmic Drugs Few choices of approved and labeled drugsFew choices of approved and labeled drugs Imperfect efficacyImperfect efficacy Adverse effects (ventricular arrhythmias)Adverse effects (ventricular arrhythmias) Electrical Cardioversion Requires conscious sedationRequires conscious sedation Complications (skin burns, aspiration, bradycardia, ventricular arrhythmia)Complications (skin burns, aspiration, bradycardia, ventricular arrhythmia) Inappropriate in some clinical situations (post-prandial, lung disease, recent cardiac surgery)Inappropriate in some clinical situations (post-prandial, lung disease, recent cardiac surgery)

6. 6 Desirable Characteristics of Pharmacologic Converting Agents Efficacy –High rate of restoring sinus rhythm with relief of symptoms –Rapid onset of action Safety –Low rate of adverse effects –Low incidence of drug interactions –Lack of interference with electrical cardioversion