Presentation on theme: "Atrial Fibrillation: A Clinical Review of the Disease State and Treatment Options DRO-042610004 Approved: 5-6-10 Lori Arnold, Pharm.D. CV/Thrombosis Regional."— Presentation transcript:
Atrial Fibrillation: A Clinical Review of the Disease State and Treatment Options DRO Approved: Lori Arnold, Pharm.D. CV/Thrombosis Regional Medical Liaison Sanofi
TAMRC # - DRO Objectives Understand the economic impact and unmet needs of Atrial Fibrillation Define the Burden of Atrial Fibrillation Describe the mechanism of Atrial Remodeling and how this contributes to the progression of Atrial Fibrillation Provide therapeutic management and guideline options for the treatment of Atrial Fibrillation
TAMRC # - DRO Clinical Presentation of Atrial Fibrillation AF presents with a wide range of symptoms 1 –May also be asymptomatic Impact of asymptomatic AF 2 –Potential for underlying electrical and structural damage to atrial myocardium While AF symptoms alone may not always be severe, untreated disease can result in significant morbidity and mortality 3 PALPITATIONS LIGHT- HEADEDNESS FATIGUE DYSPNEA SYNCOPE CHEST PAIN THROMBO- EMBOLISM DEATH 1. Fuster V et al. Circulation. 2006;114:e257-e Page RL et al. Circulation. 2003;107: Stewart S et al. Am J Med. 2002;113:
TAMRC # - DRO The ALFA Study Prevalence of Symptoms ALFA = Étude en Activité Libérale de la Fibrillation Auriculaire. Lévy S et al. Circulation. 1999;99: Total Population (N=756)
TAMRC # - DRO Burden of Atrial Fibrillation Epidemiology and Clinical Impact DRO
TAMRC # - DRO Epidemiology of Atrial Fibrillation in the US: Rising Prevalence of the Disease In 2010, 2.66 Million Americans have AF 1 Lifetime risk for developing AF is high 2 –1 in 4 for men and women aged 40 years Prevalence increases rapidly with age 1 –3.8% for persons aged 60 years –9% for persons aged 80 years AF affects 1 in 25 adults aged >60 years and 1 in 10 adults >80 years 1 Predicted Prevalence of AF 3 Projected No. of Persons With AF (millions) Year Current age-adjusted incidence Increased age-adjusted incidence Go AS et al. JAMA. 2001;285: Lloyd-Jones DM et al. Circulation. 2004;110: Miyasaka Y et al. Circulation. 2006;114:
TAMRC # - DRO And These Hospitalization Rates Are Rising… NHLBI = National Heart, Lung, and Blood Institute. NHLBI. Accessed June 1, Statistics From NHLBI ( ) Hospitalizations for AF by Primary and Secondary Diagnosis, US Hospitalizations for AF by Age Group, US Secondary diagnosis Primary diagnosis Hospitalizations (Thousands) Year Hospitalizations/10,000 Population Ages years Ages 65 years Year DRO
TAMRC # - DRO Atrial Fibrillation Adversely Affects Quality of Life* SF-36 = 36-question Short-Form health survey. *Across all scales, both the disease specific and generic QoL was significantly worse in the AF patients compared with the controls (P<0.05 compared with AF patients); Values represent raw mean scores ± SD; P<0.001 compared with AF patients. Dorian P et al. J Am Coll Cardiol. 2000;36: SF-36 Score DRO
TAMRC # - DRO Independent Risk Factors for Atrial Fibrillation* Framingham Heart Study 95% CI Men Women *2-Year pooled logistic regression; AF was diagnosed in 226 men in 16,529 follow-up person-examinations; AF was diagnosed in 244 women in 23,763 follow-up person-examinations; § Valvular heart disease was a significantly more potent risk factor for the development of atrial fibrillation in women than in men. DM = diabetes mellitus; HTN = hypertension; MI = myocardial infarction; CHF = congestive heart failure. Benjamin EJ et al. JAMA. 1994;271: Men (N=2090) Women (N=2641) P P 0.05 P P 0.01 P 0.05 P 0.01 P 0.05 P §
TAMRC # - DRO Impact of Atrial Fibrillation on Mortality...Beyond Stroke Stroke –3- to 5-fold in risk of stroke 1,2 –Stroke severity is worse with AF than without AF 3 Hypertension –In the LIFE trial, patients with hypertension and AF had higher rates of CV and all-cause mortality 4 Heart failure –Those with AF had a significantly higher mortality than those without AF (SOLVD trial) 5 Diabetes –Diabetes is an independent risk factor for AF prevalence and incidence, 6,7 and LVH, CHF, and CAD were independently associated with diabetes 6 Myocardial infarction –Several studies (eg, GISSI-3, TRACE) have shown that post-MI mortality is higher in those with AF 8,9 Sudden cardiac death –AF is an independent risk factor for sudden cardiac death 1,10 CAD = coronary artery disease; CHF = congestive heart failure; CV = cardiovascular; LVH = left ventricular dysfunction. 1. Benjamin EJ et al. Circulation. 1998;98: Fuster V et al. Circulation. 2006;114:e257-e Dulli DA et al. Neuroepidemiology. 2003;22: Wachtell K et al. J Am Coll Cardiol. 2005;45: Dries DL et al. J Am Coll Cardiol. 1998;32: Movahed MR et al. Int J Cardiol. 2005;105: Nichols GA et al. Diabetes Care. 2009;32: Pizzetti F et al. Heart. 2001;86: Pedersen OD et al. Eur Heart J. 1999;20: Middlekauff HR et al. Circulation. 1991;84:40-48.
TAMRC # - DRO Atrial Fibrillation is Linked to … Dementia/Alzheimers 1 –AF patients were 44% more likely to develop dementia –Younger patients with AF are at higher risk of developing all types of dementia, particularly Alzheimers –Patients with both AF and dementia were 61% more likely to die during study period than patients without AF Sleep Apnea 2 –Arrhythmia risk of older men rises with severity of sleep apnea and other sleep-related breathing disorders –Men with the worst respiratory disturbance at night had 2x more nocturnal AF –Growing evidence for a link between cardiac health and sleep disorders Obesity 3 –BMI was associated with short- and long-term increase in AF risk –Women becoming obese in first 60 months of study had 41% increase in risk of developing AF –Short-term elevations in BMI resulted in 18.3% increase in AF incidence –Weight control may be a reasonable strategy for reducing the growing burden of AF 1. Bunch J et al. Heart Rhythm. 2010; 7: Mehra R et al. Arch Intern Med. 2009; 169: Tedrow et al. Journal of the American College of Cardiology. 2010; 55; Tedrow et al. 3.
TAMRC # - DRO Atrial Fibrillation / Flutter Is Associated with Increased Morbidity and Mortality Death: 2-fold in risk Thromboembolism / stroke: 4.5-fold in risk Tachycardia-induced worsening of associated myocardial ischemia or heart failure Adverse atrial and ventricular remodeling due to tachycardia-induced cardiomyopathy Cardiovascular hospitalization: 2 to 3-fold in risk Krahn AD, et al al. Am J Med. 1995;98: Benjamin EJ, et al. Circulation. 1998;98: DRO
TAMRC # - DRO AF-Attributable Utilization (Annual) of Key Health Care Resources Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds MR, Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health.2006;9:348–356.
TAMRC # - DRO Economic Impact and Public Health Burden of Hospitalizations in Those With Atrial Fibrillation Significant public health burden; total AF- attributable costs estimated at 6.65 billion 1-5 Annual cost per patient ~$ Associated with more hospitalizations than any other arrhythmia 6 –Approximately one third for cardiac rhythm disturbances 1 –Increased hospitalizations impact quality of life and health care costs 2,7 1. Fuster V et al. Circulation. 2006;114:e257-e Le Heuzey J-Y et al. Am Heart J. 2004;147: Coyne KS et al. Value Health. 2006;9: Kim MH et al. Adv Ther. 2009;26: Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18: Singh SN et al. J Am Coll Cardiol. 2006;48: Wattigney WA et al. Circulation. 2003;108:
TAMRC # - DRO Goals of AF Management and Treatment *Total percentage of time a patient has AF as determined by the number and duration of AF episodes. 1. Wolf PA, et al. Stroke. 1991;22: ; 2. Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; 3. Singh SN, et al. J Am Coll Cardiol. 2006;48: ; 4. Wolf PA, et al. Arch Intern Med. 1998;158: AF management Successful management of AF should also aim at further reducing CV morbidity, mortality, and hospitalization 1-4 Prevention of thrombo- embolism Reduction of AF burden* Reduction of morbidity and mortality DRO
TAMRC # - DRO Significant Unmet Needs in the Treatment of Atrial Fibrillation Summary of AF Prevalence is rapidly increasing 1 Significantly increases CV mortality 2,3 Driver of CV hospitalizations and other health care resource utilization 4-6 Successful therapy needs reduce both symptoms and AF burden 7 AF Unmet Needs Early restoration and maintenance of sinus rhythm 8 Reduction in CV morbidity and mortality 2 Reduction in CV events and hospitalizations 6 Effective methods to maintain sinus rhythm with fewer side effects 8 CV = cardiovascular. 1. Miyasaka Y et al. Circulation. 2006;114: Wolf PA et al. Arch Intern Med. 1998;158: Haywood LJ et al. J Am Coll Cardiol. 2009;54: Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18: Kim MH et al. Adv Ther. 2009;26: Wattigney WA. Circulation. 2003;108: Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S Fuster V et al. Circulation. 2006;114:e257-e354.
TAMRC # - DRO Atrial Fibrillation is a Progressive Cardiovascular Disease The Need for Early Intervention DRO
TAMRC # - DRO What Can Cause Atrial Fibrillation? Alcohol 1 Psychological stress/Anxiety 1 Heart stimulating agents: Caffeine, Cold Medications, etc. 1 Heart surgery Heart attacks Cardiomyopathy Heart valve disease (genetic, infectious, degeneration/calcification of the valves) Pericarditis (inflammation) Hyperthyroidism Pulmonary embolism Hypertension Atrial flutter Other heart conditions that stretch, scar or thicken the heart muscle 2 1. Shea, J. A Patients Guide to Living with Atrial Fibrillation. Circulation. 2008; 117e340-e343. Available at Last accessed July 3, Fuster, V ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123: e269-e367.
TAMRC # - DRO Accessed August 13, Accessed February 5, Fuster V et al. Circulation. 2006;114:e257-e354. In AF, the heart rate may reach 100 to 175 bpm 2, and the ventricular rate may accelerate excessively during exercise even when well-controlled at rest 3 11
TAMRC # - DRO Development of Atrial Fibrillation CSO = coronary sinus ostium; CT = crista terminalis; IAS = interatrial septum; IVC = inferior vena cava; LAFW = left atrial free wall; RAA/LAA = right/left atrial appendage; RAFW = right atrium free wall; SN = sinus node; SVC = superior vena cava. 1. Narayan SM et al. Lancet. 1997;350: Fuster V et al. Circulation. 2006;114:e257-e Chen SA et al. Circulation. 1999;100: Multiple Wavelets 1,2 CSO IVC RAFW RAA LAA LAFW PV SN IASIASIASIAS Focal Triggers 2,3 SVC CT
TAMRC # - DRO Classification and Patterns of Atrial Fibrillation ACC/AHA/ESC Guidelines *Lone AF generally applies to younger individuals (<60 years) without clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension; Recurrent AF defined as 2 episodes; termination with pharmacologic or direct-current cardioversion does not change designation. Adapted from Fuster V et al. Circulation. 2006;114:e257-e354. First detected* 7 d >7 d Cardioversion failed or not attempted May be recurrent Paroxysmal (self-terminating) Persistent (not self-terminating) Permanent DRO
TAMRC # - DRO AF Disease Progression Can Lead to Cardiac Remodeling 1. Allessie M, et al. Cardiovasc Res. 2002;54: ; 2. Prystowsky EN, et al. Circulation. 1996;93: ; 3. Hobbs WJC, et al. Circulation. 2000;101: ; 4. Thijssen VLJL, et al. Cardiovasc Pathol. 2000;9:17-28; 5. Sanfilippo AJ, et al. Circulation. 1990;82: ; 6. Fuster V, et al. Circulation. 2006;114:e257-e354. Shortening of atrial refractory periods 2 Loss of normal adaptation of atrial refractoriness to heart rate 3 Reduced atrial contractility 4 Histologic changes 4 Left atrium and LA appendage enlargement 5 Decrease in cardiac output 6 Contractile 1 Structural 1 Electrical 1 DRO
TAMRC # - DRO Paroxysmal AF AF episodes 7days Spontaneous termination Persistent AF AF episodes >7 days No spontaneous termination Permanent AF AF that cannot be converted to SR The Chronic Progressive Nature of AF 1. Kirchhof P, et al. Europace. 2007;9: The State of AFib in America Survey. March-April The AF Continuum of Disease 1 AF episodeSinus rhythm (SR) Diagnosis It takes an average of 1.7 years before patients are diagnosed, leaving patients vulnerable 2 DRO
TAMRC # - DRO Atrial Fibrillation in the Cardiovascular Continuum RAAS can impact the progression of AF, and inhibition of RAAS can have some beneficial effects 3,4 HF = heart failure; LVH = left ventricular hypertrophy; MI = myocardial infarction; RAAS = renin-angiotensin- aldosterone system. 1. Fuster V et al. Circulation. 2006;114:e257-e Benjamin EJ et al. JAMA. 1994;271: Krahn AD et al. Am J Med. 1995;98: Nakashima H et al. Circulation. 2000;101: Tsai CT et al. Circulation. 2004;109: Remodeling MI Risk factors (diabetes, hypertension) LVH and atherosclerosis Ventricular dilatation HF End-stage microvascular and heart disease Death AF 1,2
TAMRC # - DRO Patients Who Convert to Sinus Rhythm Within 3 Months of Atrial Fibrillation Onset Are More Likely to Remain in Sinus Rhythm Dittrich HC et al. Am J Cardiol. 1989;63: % 36% P<0.02 DRO
TAMRC # - DRO Adopt Protocol-Driven AF Management Utilizing 2011 ACCF/AHA/HRS Guidelines Ventricular Rate Control Early Restoration of Sinus Rhythm Stroke & Thromboembolism Prevention
TAMRC # - DRO AF Treatment Options Rate Control Rhythm Control Stroke Prevention DRO
TAMRC # - DRO Rate control usually targets heart rate of bpm at rest and bpm during moderate exercise. New Recommendations for Rate Control During Atrial Fibrillation: –Treatment to achieve strict rate control of heart rate ( 0.40) and no or acceptable symptoms related to the arrhythmia, though uncontrolled tachycardia may over time be associated with a reversible decline in ventricular performance. (Level of Evidence: B) Rate Control During Atrial Fibrillation Wann LS, et al. Circulation 2011;123: DRO
TAMRC # - DRO Rhythm Control Used to maintain sinus rhythm, suppress symptoms, improve exercise capacity and hemodynamic function, and prevent tachycardia-induced cardiomyopathy due to AF 1 Restoration of sinus rhythm may prevent AF progression 2 Common agents include amiodarone, dofetilide, dronedarone, flecainide, propafenone, and sotalol Most AADs have been shown to be 50-65% effective at maintaining sinus rhythm over a 6-12 month period 3 1. Fuster V, et al. Circulation 2006;114: Bunch TJ, Gersh BJ. J Gen Intern Med 2011; May;26(5): Naccarelli GV, et al. Am J Cardiol 2003;91(suppl):15D-26D. DRO
TAMRC # - DRO ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation No (or minimal) heart disease Amiodarone Dofetilide Amiodarone Yes Maintenance of Sinus Rhythm Substantial LVH No Catheter ablation Catheter ablation Amiodarone Catheter ablation Drugs are listed alphabetically and not in order of suggested use. The seriousness of heart disease progresses from left to right, and selection of therapy in patients with multiple conditions depends on the most serious condition present. LVH indicates left ventricular hypertrophy. Dofetilide Dronedarone Sotalol Dronedarone Flecainide Propafenone Sotalol Hypertension Coronary Artery Disease Heart Failure Amiodarone Dofetilide Amiodarone Dofetilide Catheter ablation Dronedarone Flecainide Propafenone Sotalol Catheter ablation Wann LS, et al. Circulation 2011;123: DRO
TAMRC # - DRO In…A Fib, what may matter most to patients is not the risk of stroke or bleeding but rather the risks of functional and cognitive disability. Fraenkel L, et al. Individualized Medical Decision Making. Arch Intern Med. 2010; 170:
TAMRC # - DRO Atrial Fibrillation and Stroke 1. Fuster V, et al. Circulation 2006;114:e257-e Benjamin EJ, et al. Circulation 1998;98: Dulli DA, et al. Neuroepidemiology 2003;22: Page RL, et al. Circulation 2003;107: Stroke is the most common and devastating complication of AF 1,2 Incidence of all-cause stroke in patients with AF is 5% 1 AF is an independent risk factor for stroke 2 Approximately 15% of all strokes in the U.S. are caused by AF 1 Risk for stroke increases with age 1 Ischemic stroke associated with AF is often more severe than stroke from other etiology 3 Stroke risk persists even in asymptomatic AF 4 DRO
TAMRC # - DRO CHADS 2 Stroke Risk Stratification Scheme for Patients With Nonvalvular AF Relationship between CHADS 2 score and annual risk of stroke Risk factorsScore CRecent congestive heart failure1 HHypertension1 AAge 75 yrs1 DDiabetes mellitus1 S2S2 History of stroke or transient ischemic attack2 Adapted from Hersi A, et al. Curr Probl Cardiol. 2005;30:175– CHADS 2 Score Stroke Rate (%) DRO
TAMRC # - DRO Antithrombotic Therapy for AF Risk Factors 1 Recommended Therapy* No risk factorsAspirin, 81 to 325 mg daily 1 moderate-risk factor Aspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5) Any high-risk factor or >1 moderate-risk factor Warfarin (INR 2.0 to 3.0, target 2.5) 1. Fuster V, et al. Circulation. 2006;114:e257-e Wann LS, et al. Circulation. 2011;123: Connolly SJ, et al. N Engl J Med. 2009;361:1139–1151. Dabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance < 15 mL/min), or advanced liver disease (impaired baseline clotting function). 2-3 Class 1, Level of evidence B *If mechanical valve, target INR >2.5 DRO
TAMRC # - DRO Thrombotic Risk Continues in High-Risk Patients Even When SR is Maintained Antithrombotic therapy is recommended for all patients with AF, except those with lone AF or contraindications Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF It is reasonable to select antithrombotic therapy using the same criteria irrespective of the pattern (ie, paroxysmal, persistent, or permanent) of AF In high-risk AF patients, therapeutic anticoagulation should be continued SR = sinus rhythm. Fuster V et al. Circulation. 2006;114:e257-e354. III IIbIIaI B A C
TAMRC # - DRO AF Treatment Options Rate Control Rhythm Control Stroke Prevention Optimal Management Encompasses All Three Components DRO
TAMRC # - DRO Selecting Agents Initial therapy may be anticoagulation and rate control, while the long-term goal is to restore sinus rhythm Restoration of sinus rhythm becomes clear goal when rate control offers inadequate symptomatic relief Traditional agents have not demonstrated benefits in patient focused outcomes. Currently published and/or ongoing trials are demonstrating beneficial outcomes in morbidity, mortality and hospitalizations Wann LS, et al. Circulation 2011;123: DRO
TAMRC # - DRO Defining Success With Management of Atrial Fibrillation Early Intervention and Long-Term Commitment Are Required DRO
TAMRC # - DRO Defining Success With Management of Atrial Fibrillation Current common measures of success 1,2 –Any AF recurrence –Time to first recurrence of AF –Reduction of AF burden Redefining the best measure of success: reduction in AF burden and symptoms –Mortality 1 –Cardiovascular hospitalization 2 –Quality of life 3 Frequency of episodes Duration of episodes Symptoms during episodes 1. Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S Fuster V et al. Circulation. 2006;114:e257-e Wyse DG et al. Heart Rhythm. 2004;1: Dorian P et al. J Am Coll Cardiol. 2000;36:
TAMRC # - DRO Conclusion Summary of AF Prevalence is rapidly increasing 1 Significantly increases CV mortality 2,3 Driver of CV hospitalizations and other health care resource utilization 4-6 AF Unmet Needs Early restoration and maintenance of sinus rhythm 7 Reduction in CV morbidity and mortality 2 Reduction in CV events and hospitalizations 6 CV = cardiovascular. 1. Miyasaka Y et al. Circulation. 2006;114: Wolf PA et al. Arch Intern Med. 1998;158: Haywood LJ et al. J Am Coll Cardiol. 2009;54: Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18: Kim MH et al. Adv Ther. 2009;26: Wattigney WA. Circulation. 2003;108: Fuster V, et al. Circulation. 2006;114:e257-e354. DRO