Atrial Fibrillation: An Escalating Cardiovascular Disease With Significant Clinical and Economic Consequences

2

Projection for Prevalence of Atrial Fibrillation: 5.6 Million by 2050

Go AS et al. JAMA. 2001;285:2370-2375.

2.662.94

3.33

3.80

4.34

4.785.16

5.42 5.61

2.08

Ad

ult

s w

ith

atr

ial f

ibri

llati

on

in

mill

ion

s

1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050

0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Projected number of adults with atrial fibrillation in the United States between 1995 and 2050

Upper and lower curves represent the upper and lower scenarios based on sensitivity analyses.

Years

2.262.44

3

Atrial Fibrillation Is Associated With Increased Mortality

0

10

20

30

40

50

60

70

80 With atrial fibrillation Without atrial fibrillation

Cu

mu

lati

ve m

ort

alit

y o

ver

3 ye

ars

(%)

Men Women Men Women Men Women

65 to 74 years of age 75 to 84 years of age 85 to 89 years of age

38.6

30.2*34.0

25.4*

54.5

47.4* 47.5

36.1*

71.365.1*

62.4

51.0*

* Significantly different from patients with atrial fibrillation (P<.05).

Wolf PA et al. Arch Intern Med. 1998;158:229-234.

4

Atrial Fibrillation: Major Cause of Stroke in the United States

15% of all strokes attributable to atrial fibrillation

75,000 strokes per year attributable to atrial fibrillation

3- to 5-fold increase in risk of stroke in patients with atrial fibrillation

Stroke risk persists even in asymptomatic atrial fibrillation

Go AS et al. JAMA. 2001;285:2370-2375; Go AS. Am J Geriatr Cardiol. 2005;14:56-61; Wolf PA et al. Stroke. 1991;22:983-988; Benjamin EJ et al. Circulation. 1998;98:946-952; Page RL et al. Circulation. 2003;107:1141-1145.

5

Age (years) 85+ 35 to 5475 to 84 65 to 74 55 to 64

Pre

vale

nce

per

10,

000

per

son

sIncreasing Hospitalizations in the United States

When Atrial Fibrillation Is Principal Diagnosis(National Hospital Discharge Survey)

Wattigney WA et al. Circulation. 2003;108:711-716.

Year

1985 1987 1989 1991 1993 1995 1997 1999

0

20

40

60

80

100

120

140

6

Atrial Fibrillation Adversely Affects Quality of Life (QoL)

Lower scores = poorer QoL

Dorian P et al. J Am Coll Cardiol. 2000;36:1303-1309.

SF

-36

sco

re

54

68 71 68

59

70

85

7678

8892

81

0

20

40

60

80

100

120

General health Physicalfunction

Social function Mental health

Atrial fibrillation

Post myocardialinfarction

Controls

7

Hobbs WJC et al. Circulation. 2000;101:1145-1151; Sanfilippo AJ et al. Circulation. 1990;82:792-797; Thijssen VLJL et al. Cardiovasc Pathol. 2000;9:17-28; Van Gelder IC et al. Europace. 2006;8:943-949; Peters NS et al. Lancet. 2002;359:593-603.

Atrial Fibrillation Causes Several Types of Remodeling Over Time That Have Adverse Physiologic Consequences

Electrophysiologic changes – Shortening of atrial refractory periods– Loss of normal adaptation of atrial refractoriness

to heart rate

Contractile changes– Reduced atrial contractility

Structural changes– Left atrium and left atrial appendage enlargement– Decrease in cardiac output– Histologic changes

Prothrombotic changes (increased propensity for clot formation)– Atrial stasis– Increases prothrombotic factors

8

Myolysis

Connexin 40

Sinus rhythm Atrial fibrillation

Ausma J et al. Circulation. 1997;96:3157-3163; Van der Velden HMW et al. J Cardiovasc Electrophysiol. 1998;9:596-607.

Atrial Fibrillation Causes Histologic Remodeling of Atria as Early as 4 Months

Enlarged atrial cells Severe myolysis Glycogen accumulation

Reduction in connexin 40 expression

9

Patients Converted to Sinus Rhythm Within 3 Months of Onset Are More Likely to Remain in Sinus Rhythm

0

10

20

30

40

50

60

70

80

90 <3-month duration of atrial fibrillation prior to cardioversion

>12-month duration of atrial fibrillation prior to cardioversion

Pat

ien

ts in

sin

us

rhyt

hm

(%

)

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

67%

27%

The longer one waits to initiate a rhythm-control strategy, the harder it is to regain sinus rhythm

82%

36%

1 monthP<.02

6 monthsP<.07

11

Long-term Maintenance of Sinus Rhythm Improves Functional Capacity: AFFIRM Mean New York Heart Association functional

class (NYHA-FC) score significantly better at each visit in patients in sinus rhythm

Chung MK et al. J Am Coll Cardiol. 2005;46:1891-1899.

Months Years

0.50

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Mea

n N

YH

A-F

C s

core

(Lower NYHA-FC score = less symptomatic)Adjusted P<.0001

Initial 2 4 8 1 1⅓ 1⅔ 2 2⅓ 2⅔ 3 3⅓ 3⅔ 4 4⅓ 4⅔ 5

Current atrial fibrillation

No current atrial fibrillation

12

Decreasing Atrial Fibrillation Burden Is an Important Goal

As with heart failure or angina, success in managing atrial fibrillation is defined as a decrease in:

Decreasing atrial fibrillation burden offers potential to successfully treat atrial fibrillation by:– Decreasing mortality– Decreasing hospitalizations– Increasing QoL

Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; Wolf PA et al. Arch Intern Med. 1998;158:229-234.

Frequency of

episodes

Frequency of

episodes

Duration of

episodes

Duration of

episodes

Symptomsduring

episodes

Symptomsduring

episodes

13

Summary Atrial fibrillation is a chronic, cardiovascular disease with increasing

socioeconomic impact– Prevalence of atrial fibrillation is projected to be 5.6 million by 2050– Atrial fibrillation is associated with increased risk of mortality, risk of stroke, and

compromised QoL– Hospitalizations for atrial fibrillation have increased 2- to 3-fold and are projected to

continue rising

Early restoration and maintenance of sinus rhythm has an integral role in overall atrial fibrillation treatment strategy

– Atrial fibrillation causes several types of remodeling over time that have adverse physiologic consequences

• Atrial fibrillation causes histologic remodeling of the atria as early as 4 months– Sustaining sinus rhythm may be associated with decreased mortality

Decreasing atrial fibrillation burden offers potential to successfully treat atrial fibrillation

– As with other chronic cardiovascular diseases, successful management of atrial fibrillation includes an overall reduction in frequency and duration of episodes, while reducing symptoms during episodes

– A measure of success can be defined by decreased mortality, decreased hospitalizations, and increased QoL