Atrial Fibrillation: A Clinical Review of the

Disease State and Treatment Options

DRO-042610004Approved: 5-6-10

Lori Arnold, Pharm.D.CV/Thrombosis Regional Medical Liaison

Sanofi

TAMRC # - DRO-042610004

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-042610004

Clinical Presentation of Atrial Fibrillation

• AF presents with a wide range of symptoms1

– May also be asymptomatic

• Impact of asymptomatic AF2

– 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 mortality3

PALPITATIONSLIGHT-HEADEDNESS

FATIGUE

DYSPNEASYNCOPE

CHEST PAIN

THROMBO-EMBOLISM

DEATH

1. Fuster V et al. Circulation. 2006;114:e257-e354. 2. Page RL et al. Circulation. 2003;107:1141-1145. 3. Stewart S et al. Am J Med. 2002;113:359-364.

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The ALFA StudyPrevalence of Symptoms

ALFA = Étude en Activité Libérale de la Fibrillation Auriculaire.Lévy S et al. Circulation. 1999;99:3028-3035.

54.1

10.1

44.4

10.414.3

0.9

11.4

0

10

20

30

40

50

60

Palpitations Chest Pain Dyspnea Syncope,Dizzy Spells

Fatigue Other None

Type of Symptoms

Perc

ent

Total Population(N=756)

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Burden of Atrial Fibrillation

Epidemiology and Clinical Impact

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TAMRC # - DRO-042610004Epidemiology of Atrial Fibrillation in the US:

Rising Prevalence of the Disease

• In 2010, 2.66 Million Americans have AF1

• Lifetime risk for developing AF is high2

– 1 in 4 for men and women aged 40 years

• Prevalence increases rapidly with age1

– 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 years1

Predicted Prevalence of AF3

Pro

jecte

d N

o.

of

Pers

on

sW

ith

AF (

million

s)

2000 2005201020152020202520302035204020452050

Year

16

14

12

10

6

8

2

4

0

Current age-adjusted incidence

Increased age-adjusted incidence

5.1 5.6 6.16.8

7.58.4

9.410.3

11.111.7 12.1

5.15.9

6.77.7

8.9

10.2

11.7

13.1

14.3

15.215.9

1. Go AS et al. JAMA. 2001;285:2370-2375.2. Lloyd-Jones DM et al. Circulation. 2004;110:1042-1046.3. Miyasaka Y et al. Circulation. 2006;114:119-125.

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19951985 2005

And These Hospitalization Rates Are Rising…

NHLBI = National Heart, Lung, and Blood Institute.

NHLBI. http://www.nhlbi.nih.gov/resources/docs/cht-book.htm. Accessed June 1, 2009.

Statistics From NHLBI (1982-2006)

Hospitalizations for AF by Primary and Secondary Diagnosis, USHospitalizations for AF by Age Group, US

1980

3000

Secondary diagnosis

Primary diagnosis

Hosp

italizati

on

s (

Th

ou

san

ds)

Year

2500

2000

1500

1000

500

1990 2000

Hosp

italizati

on

s/1

0,0

00

Pop

ula

tion

1982 1987 1992 1997 2000

100

80

60

40

20

0

Ages 45-64 years

Ages 65 years

Year

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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;36:1303-1309.

54

6871

68

59

70

85

7678

8892

81

0

20

40

60

80

100

GeneralHealth

PhysicalFunctioning

SocialFunctioning

Mental Health

Atrial fibrillation

Post-MI

Healthy subjects

‡‡

†‡

‡‡

‡

SF-3

6 S

core

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TAMRC # - DRO-042610004Independent Risk Factors for Atrial Fibrillation* Framingham Heart

Study

95% CI

Men 1.8-2.5 1.0-2.0 1.2-2.0 1.0-2.0 3.1-6.6 1.2-2.5

Women 1.9-2.6 1.1-1.2 1.1-1.8 0.8-1.8 4.2-8.4 2.5-4.5*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;271:840-844.

0

1

2

3

4

5

6

7

Age (per 10 y)

DM HTN MI CHF ValveDisease

OR

Men† (N=2090)

Women‡ (N=2641)

P0.0001

P0.05

P0.0001

P0.0001

P0.0001

P0.01 P0.01P0.05

P0.01P0.05

P0.0001

§

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Impact of Atrial Fibrillation on Mortality. . .Beyond Stroke

• Stroke– 3- to 5-fold in risk of stroke1,2

– Stroke severity is worse with AF than without AF3

• Hypertension – In the LIFE trial, patients with

hypertension and AF had higher rates of CV and all-cause mortality4

• 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 diabetes6

• Myocardial infarction – Several studies (eg, GISSI-3, TRACE)

have shown that post-MI mortality is higher in those with AF8,9

• Sudden cardiac death– AF is an independent risk factor for

sudden cardiac death1,10

CAD = coronary artery disease; CHF = congestive heart failure; CV = cardiovascular; LVH = left ventricular dysfunction.1. Benjamin EJ et al. Circulation. 1998;98:946-952. 2. Fuster V et al. Circulation. 2006;114:e257-e354. 3. Dulli DA et al. Neuroepidemiology. 2003;22:118-123. 4. Wachtell K et al. J Am Coll Cardiol. 2005;45:705-711. 5. Dries DL et al. J Am Coll Cardiol. 1998;32:695-703. 6. Movahed MR et al. Int J Cardiol. 2005;105:315-318. 7.Nichols GA et al. Diabetes Care. 2009;32:1851-1856. 8. Pizzetti F et al. Heart. 2001;86:527-532. 9. Pedersen OD et al. Eur Heart J. 1999;20:748-754. 10. Middlekauff HR et al. Circulation. 1991;84:40-48.

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Atrial Fibrillation is Linked to …• Dementia/Alzheimer’s1

– AF patients were 44% more likely to develop dementia

– Younger patients with AF are at higher risk of developing all types of dementia, particularly Alzheimer’s

– Patients with both AF and dementia were 61% more likely to die during study period than patients without AF

• Sleep Apnea2

– 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

• Obesity3

– 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: 433-437. 2. Mehra R et al. Arch Intern Med. 2009; 169: 1147-55.3. Tedrow et al. Journal of the American College of Cardiology. 2010; 55; 2319-2327. 3. Tedrow et al. 3.

TAMRC # - DRO-042610004Atrial 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;98:476-484 Benjamin EJ, et al. Circulation. 1998;98:946-952.

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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-042610004Economic Impact and Public Health Burden of Hospitalizations in Those With Atrial

Fibrillation

•Significant public health burden; total AF-attributable costs estimated at 6.65 billion1-5

•Annual cost per patient ~$47005

•Associated with more hospitalizations than any other arrhythmia6

– Approximately one third for cardiac rhythm disturbances1

– Increased hospitalizations impact quality of life and health care costs2,7

1. Fuster V et al. Circulation. 2006;114:e257-e354. 2. Le Heuzey J-Y et al. Am Heart J. 2004;147:121-126. 3. Coyne KS et al. Value Health. 2006;9:348-356. 4. Kim MH et al. Adv Ther. 2009;26:847-857. 5. Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18:628-633. 6. Singh SN et al. J Am Coll Cardiol. 2006;48:721-730. 7. Wattigney WA et al. Circulation. 2003;108:711-716.

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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;22:983-988; 2. Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; 3. Singh SN, et al. J Am Coll Cardiol. 2006;48:721-730; 4. Wolf PA, et al. Arch Intern Med. 1998;158:229-234.

AF management

Successful management of AF should also aim at further reducing CV morbidity, mortality, and hospitalization1-4

Prevention ofthrombo-embolism

Reduction of AF burden*

Reduction of morbidity

and mortality

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Significant Unmet Needs in the Treatment of Atrial Fibrillation

Summary of AF• Prevalence is rapidly

increasing1

• Significantly increases CV mortality2,3

• Driver of CV hospitalizations and other health care resource utilization4-6

• Successful therapy needs reduce both symptoms and AF burden7

AF Unmet Needs• Early restoration and

maintenance of sinus rhythm8

• Reduction in CV morbidity and mortality2

• Reduction in CV events and hospitalizations6

• Effective methods to maintain sinus rhythm with fewer side effects8

CV = cardiovascular.1. Miyasaka Y et al. Circulation. 2006;114:119-125. 2. Wolf PA et al. Arch Intern Med. 1998;158:229-234. 3. Haywood LJ et al. J Am Coll Cardiol. 2009;54:2023-2031. 4. Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18:628-633. 5. Kim MH et al. Adv Ther. 2009;26:847-857. 6. Wattigney WA. Circulation. 2003;108:711-716. 7. Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10. 8. Fuster V et al. Circulation. 2006;114:e257-e354.

TAMRC # - DRO-042610004

Atrial Fibrillation is a Progressive Cardiovascular

Disease

The Need for Early Intervention

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What Can Cause Atrial Fibrillation?• Alcohol1

• Psychological stress/Anxiety1

• 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 muscle2

1. Shea, J. A Patient’s Guide to Living with Atrial Fibrillation. Circulation. 2008; 117e340-e343. Available at http://circ.ahajournals.org/cgi/content/full/117/20/e340. Last accessed July 3, 2008.2. Fuster, V. 2011 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-042610004

1. http://www.mahalo.com/Atrial_Fibrillation. Accessed August 13, 2009. 2. http://www.nlm.nih.gov/medlineplus/ency/article/000184.htm. Accessed February 5, 2010. 3. Fuster V et al. Circulation. 2006;114:e257-e354.

In AF, the heart rate may reach 100 to 175 bpm2, and the ventricular rate may accelerate excessively during exercise even when well-

controlled at rest3

11

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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;350:943-950. 2. Fuster V et al. Circulation. 2006;114:e257-e354. 3. Chen SA et al. Circulation. 1999;100:1879-1886.

Multiple Wavelets1,2

CSOCSO

IVCIVC

RAFRAFWW

RAARAA LAALAA

LAFWLAFW

PPVV

SSNN

IIA A SS

Focal Triggers2,3

SVCSVC

CTCT

TAMRC # - DRO-042610004Classification 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

Cardioversion failed or

not attempted

May be recurrent†Paroxysmal

(self-terminating)Persistent

(not self-terminating)

Permanent

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AF Disease Progression Can Lead to Cardiac Remodeling

1. Allessie M, et al. Cardiovasc Res. 2002;54:230-246; 2. Prystowsky EN, et al. Circulation. 1996;93:1262-1277; 3. Hobbs WJC, et al. Circulation. 2000;101:1145-1151; 4. Thijssen VLJL, et al. Cardiovasc Pathol. 2000;9:17-28; 5. Sanfilippo AJ, et al. Circulation. 1990;82:792-797; 6. Fuster V, et al. Circulation. 2006;114:e257-e354.

• Shortening of atrial refractory periods2

• Loss of normal adaptation of atrial refractoriness to heart rate3

• Reduced atrial contractility4

• Histologic changes4

• Left atrium and LA appendage enlargement5

• Decrease in cardiac output6

Contractile1 Structural1

Electrical1

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Paroxysmal AFAF episodes ≤7days

Spontaneous termination

Persistent AFAF episodes >7 days

No spontaneous termination

Permanent AFAF that cannot be converted to SR

The Chronic Progressive Nature of AF

1. Kirchhof P, et al. Europace. 2007;9:1006-1023. 2. The State of AFib in America Survey. March-April 2009. http://www.afstat.com/AF_Stat_Resources/Out_of_Sync_Survey.aspx

The AF Continuum of Disease1

AF episodeSinus rhythm (SR)

Diagnosis

It takes an average of 1.7 years before patients are diagnosed, leaving patients vulnerable2

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Atrial Fibrillation in theCardiovascular Continuum

RAAS can impact the progression of AF,and inhibition of RAAS can have some beneficial

effects3,4HF = heart failure; LVH = left ventricular hypertrophy; MI = myocardial infarction; RAAS = renin-angiotensin-aldosterone system.1. Fuster V et al. Circulation. 2006;114:e257-e354. 2. Benjamin EJ et al. JAMA. 1994;271:840-844. 3. Krahn AD et al. Am J Med. 1995;98:476-484. 4. Nakashima H et al. Circulation. 2000;101:2612-2617. 5. Tsai CT et al. Circulation. 2004;109:1640-1646.

Remodeling

MI

Risk factors(diabetes,

hypertension)

LVH and atherosclerosis

Ventriculardilatation

HF

End-stage microvascular and

heart disease

Death

AF1,2

TAMRC # - DRO-042610004Patients Who Convert to Sinus Rhythm

Within 3 Months of Atrial Fibrillation Onset Are More Likely to Remain in Sinus Rhythm

0

10

20

30

40

50

60

70

80

90

Initial 1 month 6 months

Sin

us

Rhyt

hm

, %

<3 months 3-12 months >12 months

Dittrich HC et al. Am J Cardiol. 1989;63:193-197.

82%

36%

P<0.02

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Adopt Protocol-Driven AF Management Utilizing

2011 ACCF/AHA/HRS Guidelines

•Ventricular Rate Control•Early Restoration of Sinus Rhythm

•Stroke & Thromboembolism Prevention

TAMRC # - DRO-042610004

AF Treatment Options

Rate Control

Rhythm Control

StrokePrevention

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• Rate control usually targets heart rate of 60-80 bpm at rest and 90-115 bpm during moderate exercise.

• New Recommendations for Rate Control During Atrial Fibrillation:– Treatment to achieve strict rate control of heart rate (<80

bpm at rest or <110 bpm during a 6-minute walk) is not beneficial compared to achieving a resting heart rate of <110 bpm in patients with persistent AF who have stable ventricular function (left ventricular ejection fraction >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;123:1144-1150.

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Rhythm Control

• Used to maintain sinus rhythm, suppress symptoms, improve exercise capacity and hemodynamic function, and prevent tachycardia-induced cardiomyopathy due to AF1

• Restoration of sinus rhythm may prevent AF progression2

• 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 period3

1. Fuster V, et al. Circulation 2006;114:257-354.2. Bunch TJ, Gersh BJ. J Gen Intern Med 2011; May;26(5):531-73. Naccarelli GV, et al. Am J Cardiol 2003;91(suppl):15D-26D.

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2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial

Fibrillation

No (or minimal)heart disease

AmiodaroneDofetilide

Amiodarone

Yes

Maintenance of Sinus Rhythm

Substantial LVH

No

Catheterablation

Catheterablation

Amiodarone Catheterablation

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.

DofetilideDronedarone

Sotalol

DronedaroneFlecainide

PropafenoneSotalol

Hypertension Coronary ArteryDisease Heart Failure

AmiodaroneDofetilide

AmiodaroneDofetilide

Catheterablation

DronedaroneFlecainide

PropafenoneSotalol

Catheterablation

Wann LS, et al. Circulation 2011;123:104-23.

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“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: 566-569.

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Atrial Fibrillation and Stroke

1. Fuster V, et al. Circulation 2006;114:e257-e354. 2. Benjamin EJ, et al. Circulation 1998;98:946-52.3. Dulli DA, et al. Neuroepidemiology 2003;22:118-23. 4. Page RL, et al. Circulation 2003;107:1141-5.

• Stroke is the most common and devastating complication of AF1,2

Incidence of all-cause stroke in patients with AF is 5%1

• AF is an independent risk factor for stroke2

Approximately 15% of all strokes in the U.S. are caused by AF1

Risk for stroke increases with age1

• Ischemic stroke associated with AF is often more severe than stroke from other etiology3

• Stroke risk persists even in asymptomatic AF4

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TAMRC # - DRO-042610004CHADS2 Stroke Risk Stratification Scheme

for Patients With Nonvalvular AF

Relationship between CHADS2 score and annual risk of stroke

Risk factors Score

C Recent congestive heart failure 1

H Hypertension 1

A Age ≥75 yrs 1

D Diabetes mellitus 1

S2 History of stroke or transient ischemic attack 2

Adapted from Hersi A, et al. Curr Probl Cardiol. 2005;30:175–234.

1.9 2.84.0

5.98.5

12.5

18.2

0.0

5.0

10.0

15.0

20.0

0 1 2 3 4 5 6

CHADS2 Score

Str

ok

e R

ate

(%

)

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Antithrombotic Therapy for AFRisk Factors1 Recommended Therapy*

No risk factors Aspirin, 81 to 325 mg daily

1 moderate-risk factorAspirin, 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-e354.

2. Wann LS, et al. Circulation. 2011;123:1144-1150.

3. 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

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TAMRC # - DRO-042610004Thrombotic 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.

IIIIIbIIaI

B

A

C

TAMRC # - DRO-042610004

AF Treatment Options

Rate Control

RhythmControl

StrokePrevention

Optimal Management Encompasses All

Three Components

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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;123:104-23.

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Defining Success With Management of Atrial

Fibrillation

Early Intervention and Long-Term Commitment Are Required

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Defining Success With Management of Atrial Fibrillation

• Current common measures of success1,2

– 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– Mortality1

– Cardiovascular hospitalization2

– Quality of life3

Frequency of

episodes

Frequency of

episodes

Duration of

episodes

Duration of

episodes

Symptomsduring

episodes

Symptomsduring

episodes

1. Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10. 2. Fuster V et al. Circulation. 2006;114:e257-e354. 3. Wyse DG et al. Heart Rhythm. 2004;1:531-537. 4. Dorian P et al. J Am Coll Cardiol. 2000;36:1303-1309.

TAMRC # - DRO-042610004

Conclusion

Summary of AF• Prevalence is rapidly

increasing1

• Significantly increases CV mortality2,3

• Driver of CV hospitalizations and other health care resource utilization4-6

AF Unmet Needs• Early restoration and

maintenance of sinus rhythm7

• Reduction in CV morbidity and mortality2

• Reduction in CV events and hospitalizations6

CV = cardiovascular.1. Miyasaka Y et al. Circulation. 2006;114:119-125. 2. Wolf PA et al. Arch Intern Med. 1998;158:229-234. 3. Haywood LJ et al. J Am Coll Cardiol. 2009;54:2023-2031. 4. Reynolds MR et al. J Cardiovasc Electrophysiol. 2007;18:628-633. 5. Kim MH et al. Adv Ther. 2009;26:847-857. 6. Wattigney WA. Circulation. 2003;108:711-716. 7. Fuster V, et al. Circulation. 2006;114:e257-e354.

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