1. Epidemiology and burden of atrial fibrillation and associated stroke
Module 1

2. Epidemiology of atrial fibrillation

3. AF is a common disorder
AF is an arrhythmia responsible for one-third of all hospitalizations for cardiac rhythm disturbances1
Estimated prevalence rates for AF:
Europe: 4.5 million1
USA: 5.1 million2
Approximately 2.5% of the US population are affected by AF2
Nearly one in four people at age 55 years will go on to develop AF (24% of men and 22% of women)3
1. ACC/AHA/ESC guidelines: Fuster V et al. Circulation 2006;114:e257–354 & Eur Heart J 2006;27:1979–2030; 2. Miyasaka Y et al. Circulation 2006;114:119–25; 3. Heeringa J et al. Eur Heart J 2006;27:949–53

4. Prevalence of AF predicted to more than double by 20508 10 12 16
2050
People with AF in the US (millions)
Year
2000
2010
2020
2030
2040 6 4 2 14
Figure reproduced with permission: ©2009, American College of Cardiology, Inc
Projected incidence of AF assuming a continued increase in age-adjusted incidence as evident in 1980–2000
Projected incidence of AF assuming no further increase in age-adjusted incidence
Miyasaka Y et al. Circulation 2006;114:119–25

5. Prevalence of AF increases with age
Age (yrs)
Prevalence (%) 5 10 15 20
55–59
60–64
65–69
70–74
75–79
80–84
>85
Women (n=4053)
Men (n=2590)
Prevalence at baseline assessed in 6808 participants in a European population-based study
Data from Heeringa J et al. Eur Heart J 2006;27:949–53

6. AF is an increasingly common disorder
The overall prevalence of AF is increasing, driven by:
Ageing of populations worldwide
Rising prevalence of chronic heart disease
Rising prevalence of AF risk factors, e.g. diabetes mellitus
The number of people with diagnosed AF in industrialized countries (US, Japan, Germany, Italy, France, UK and Spain) is expected to rise from 6.3 million in 2007 to million in 20171
Hospital admissions for AF have increased by 60% over the past 20 years2
1. Benyoucef S et al. Atrial fibrillation. 2008; available at: accessed Feb 2010; 2. Friberg J et al. Epidemiology 2003;14:666–72

7. Epidemiology of stroke in patients with atrial fibrillation

8. Stroke is a frequent complication of AF
Stroke is the leading complication of AF
AF is associated with a 5-fold higher stroke risk overall1
AF doubles the risk of stroke when adjusted for other risk factors2
Without preventive treatment, each year approximately 1 in 20 patients (5%) with AF will have a stroke3
When transient ischaemic attacks and clinically ‘silent’ strokes are considered, the rate of brain ischaemia associated with non-valvular AF exceeds 7% per year4
AF is responsible for nearly one-third of all strokes,5 and AF is the leading cause of embolic stroke6
1. Savelieva I et al. Ann Med 2007;39:371–91; 2. ACC/AHA/ESC guidelines: Fuster V et al. Circulation 2006;114:e257–354 & Eur Heart J 2006;27:1979–2030; 3. Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–57; 4. Carlson M. Medscape Cardiology. 2004;8; available at accessed Feb 2010; 5. Hannon N et al. Cerebrovasc Dis 2010;29:43–9; 6. Atrial fibrillation; available at accessed 17 Feb 2010

9. Stroke is a serious complication of AF
Stroke in AF is associated with a heavy burden of morbidity and mortality
AF stroke is usually more severe than stroke due to other causes1
Compared with other stroke patients, those with AF are more likely to:2
Have cortical deficit (e.g. aphasia)
Have severe limb weakness
Have diminished alertness
Be bedridden on admission
The mortality rate for patients with AF is double that in people with normal heart rhythm3
1. Savelieva I et al. Ann Med 2007;39:371–91; 2. Dulli DA et al. Neuroepidemiology 2003;22:118–23; 3. Benjamin EJ et al. Circulation 1998;98:946–52

10. Incidence of stroke in AF patients increases with age
Incidence of stroke after diagnosis of AF (men)
Incidence of stroke per 1000 person-years
Age (yrs) 45
40–44
85–89
45–49
50–54
55–59
60–64
65–69
70–74
75–79
80–84 40 35 30 25 20 15 10 5
22-year follow-up of men in the Danish National Registry of Patients 10
Frost L et al. Neuroepidemiology 2007;28:109–15 10

11. Stroke risk persists even in asymptomatic/paroxysmal AF
The risk of stroke with asymptomatic or paroxysmal AF is comparable to that with permanent AF1,2
Observed rate of ischaemic stroke1
Annual risk of stroke (%)
Stroke risk category
Low
Moderate
High 2 4 6 8 10 12 14
Intermittent AF
Sustained AF
1. Hart RG et al. J Am Coll Cardiol 2000;35:183–7; Flaker GC et al. Am Heart J 2005;149:657–63

12. Risk factors for stroke in patients with AF

13. The risk of stroke varies widely from patient to patient
Risk of stroke depends on a range of factors1
Annual stroke rates can vary 20-fold with no vs. multiple risk factors2
Increasing age*
Prior stroke or TIA
Relative risk of stroke
3.0
2.0
1.0
History of diabetes
History of hypertension
History of heart failure
Risk factor
*Relative risks are based on decades of age
1. Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–57;
2. Gage BF et al. JAMA 2001;285:2864–70

14. Framingham risk score: relation to 5-year stroke risk
5-yr risk of stroke (%)
Framingham risk score
100 80 60 40 20 35 5 10 15 25 30
Risk score based on:
Age
Gender
SBP
Diabetes
Prior stroke/TIA
SBP = systolic blood pressure; TIA = transient ischaemic attack
Data from Wang TJ et al. JAMA 2003;290:1049–56

15. Annual risk for stroke in AF
Stroke risk category
Low
Moderate
High (no prior stroke/TIA)
High (prior stroke/TIA)
Overall 2 4 6 8 10 12 14
Review of 13 randomized trials of antithrombotic therapy; TIA = transient ischaemic attack
Data from Hart RG et al. Neurology 1998;51:674–81

16. Importance of stroke risk assessment in patients with AF
Antithrombotic therapy reduces the risk of stroke in AF patients but also carries a risk of bleeding complications
Absolute reduction in stroke rates is greatest in patients at highest risk of stroke
High-risk patients benefit from intensive antithrombotic treatment
Risk of major bleeding as a complication of antithrombotic treatment is similar across stroke risk groups
Low-risk patients may not gain sufficient benefit from oral anticoagulant therapy to outweigh the risk of bleeding and need for close monitoring
van Walraven C et al. JAMA 2002;288:2441–8;
van Walraven C et al. Arch Intern Med 2003;163:936–43

17. Estimation of stroke risk in AF
Classification scheme
Patient population
Risk factors identified
Atrial Fibrillation Investigators1
Five randomized studies
N=1593, 106 strokes over a mean follow up 1.4 yrs
Age
Hypertension
Prior cerebral ischaemia
Diabetes
Stroke Prevention and Atrial Fibrillation (SPAF)2
Two randomized studies
N=854, 68 strokes over a mean follow up 2.3 yrs
Blood pressure >160 mmHg
Recent heart failure
Combination of age ≥75 yrs and female gender
Framingham Heart Study3
Recently identified AF
N=705
Female gender
1. Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–57; 2. SPAF. J Stroke Cerebrovasc Dis 1995;5:147–57; 3. Wang TJ et al. JAMA 2003;290:1049–56

18. Estimation of stroke risk in AF: CHADS2
Validated using the National Registry of Atrial Fibrillation (NRAF)
Most widely used to guide the choice of antithrombotic therapy
CHADS2 risk criteria
Score
Cardiac failure 1
Hypertension
Age ≥75 yrs
Diabetes mellitus
Stroke or TIA (previous history) 2
TIA = transient ischaemic attack
Gage BF et al. JAMA 2001;285:2864–70

19. Estimation of stroke risk in AF using CHADS2
Annual stroke rate (%)
CHADS2 score 30 2 3 4 5 6 10 15 20 25 1
Error bars around each point = 95% CI
Data from Gage BF et al. JAMA 2001;285:2864–70

20. Summary

21. Summary AF is the most common cardiac arrhythmia
Prevalence of AF is increasing
AF increases the risk of stroke 5-fold and is responsible for nearly one-third of all strokes
Risk of stroke persists in asymptomatic or paroxysmal AF
Factors increasing stroke risk include:
Previous stroke or transient ischaemic disease
Advancing age
Chronic heart disease
Rheumatic valvular disease or prosthetic valve
Hypertension
Diabetes mellitus
Assessment of stroke risk is important to guide antithrombotic therapy

22. The burden and costs of atrial fibrillation

23. AF is associated with substantial healthcare costs
Total annual medical costs of AF in the US estimated as US$6.65 billion (2001)
Healthcare resource utilization included:
hospitalizations
emergency department visits
outpatient visits
The bulk of costs related to direct and indirect inpatient care
23%
44% 4%
29%
Direct inpatient
Indirect inpatient
Drugs
Outpatient
Coyne KS et al. Value Health 2006;9:348–56

24. Costs to the EU economy
AF costs an estimated €6.2 billion across the EU each year (EuroHeart Study, 2003–2004 data)
Equates to €1500–3200 per patient each year
Greece
Italy
Poland
Spain
The Netherlands
Mean annual cost (€/patient)
1507
3225
1010
2315
2328
Total country costs (€ million)
272
3286
526
1545
554
Ringborg A et al. Europace 2008;10:403–11

25. Per patient costs of AF in the EU
Healthcare costs associated with AF are high across European countries
Annual per patient costs estimated as:
€3209 in France1
Cost drivers included hospitalizations (52%), drugs (23%) and consultations (9%)
€827 in Germany2
50% of total costs were incurred by 11% of patients and driven by AF-related hospitalizations (44%)
€680 in the UK3
Representing nearly 1% of the total budget of the National Health Service (2000 data)
1. Le Heuzey JY et al. Am Heart J 2004;147:121–6; 2. McBride D et al. Value Health 2008;12:293–301; 3. Stewart S et al. Heart 2004;90:286–92

26. Per patient costs of AF in the USA
Average annual per patient costs of US$4000–5000
Costs increase with the number of AF recurrences
3 (n=33)
Annual cost of AF-related medical care (US$)
Documented recurrences
0 (n=620)
12 000
10 000
8000
6000
4000
2000
Permanent AF (n=34)
1–2 (n=286)
Hospital costs
P<0.05
Outpatient costs
Drug costs
P<0.05
Reynolds MR et al. J Cardiovasc Electrophysiol 2007;18:628–33

27. AF also incurs a significant personal burden
In addition to societal costs, quality of life is worse in patients with AF versus other cardiac conditions
SF-36 quality-of-life scores
SF-36 score
General health
Physical functioning
Role physical
Vitality
Mental health
Role emotional
Social functioning
Bodily pain 20 40 60 80
100 AF
(n=152)
Post-MI
(n=69)
Healthy
subjects
(n=69)
MI = myocardial infarction; SF = Short Form
Data from Dorian P et al. J Am Coll Cardiol 2000;36:1303–9

28. AF has serious consequences
AF is associated with a number of serious and potentially life-threatening complications including stroke,1,2 heart failure2 and death2,3
Cardiovascular hospitalizations or death2
Age-adjusted event-free survival probability
1.0
Follow-up (yrs) 20
0.8
0.6
0.4
0.2
0.0 2 4 6 8 10 12 14 16 18
Women without AF
Men without AF
Men with AF
Women with AF
1. Wolf PA et al. Stroke 1991;22:983–8; 2. Stewart S et al. Am J Med 2002;113:259–64; 3. Benjamin E et al. Circulation 1998;98:946–52

29. The burden of stroke associated with atrial fibrillation

30. Stroke is more likely to be fatal in patients with AF
Stroke is more likely to be fatal in patients with AF (AF vs. non-AF: P=0.048)
Stroke severity
Proportion of patients (%) 5 10 15 20 25 30
None
Mild
Moderate
Severe
Fatal
AF (n=103)
Non-AF (n=398)
Lin HJ et al. Stroke 1996;27:1760–4

31. Stroke severity increases the length of hospital stay
Length of hospital stay for survivors according to stroke severity
Length of hospital stay (days)
120
Initial stroke severity*
100 80 60 40 20 55 5 10 15 25 30 35 45 50
More severe
Less severe
1197 acute stroke patients participating in the Copenhagen Stroke Study; *Scandinavian Neurological Stroke Score on admission
Jorgensen HS et al. Stroke 1997;28:1138–41

32. Clinical assessment scales in stroke
Scandinavian Stroke Scale (SSS):1
Consciousness − Eye movement
Motor power – arm, hand and leg − Orientation
Speech − Facial palsy
Gait
Barthel Index:2
Feeding − Bathing
Grooming − Dressing
Bowels − Bladder
Transfers (bed to chair and back) − Toilet use
Mobility (level surface) − Stairs
1. Scandinavian Stroke Study Group. Stroke 1985;16:885–90;
2. Mahoney FI, Barthel DW. Md State Med J 1965;14:61–5

33. Stroke survivors with AF have poorer outcomes
Outcome measure
Patients with AF
Patients without AF
Initial stroke severity (SSS score*) 30 38
Initial disability (BI score*) 35 52
Length of hospital stay (days) 50 40
Inhospital mortality (%) 33 17
Discharged to nursing home (%) 19 14
Neurological outcome (SSS score*) 46
Functional outcome (BI score*) 67 78
* Lower scores are associated with a poorer prognosis; SSS = Scandinavian Neurological Stroke Score (maximum long-term score = 48); BI = Barthel Index (maximum score = 100)
Jorgensen HS et al. Stroke 1996;27:1765–9

34. Increased risk of death after stroke in patients with AF persists for up to 8 years
Years post-stroke
Annual mortality rate (%) 10 20 30 40 50 60
Mortality 1 2 3 4 5 6 7 8
Patients with AF
Patients without AF
Population-based study of 3530 patients with ischaemic stroke
Marini C et al. Stroke 2005;36:1115–9

35. AF patients face an increased risk of recurrent stroke
Months after first stroke
Cumulative probability of recurrence (%) 10 12 8 6 4 2
Patients with AF
Patients without AF
P=0.0398
Marini C et al. Stroke 2005;36:1115–9

36. Stroke survivors face persistent disability
Proportion of patients (%) 50 40 30 20 10
Disability 6 months post-stroke (all types)
ADL (BI <60)
Unable to walk unassisted
Bladder
incontinence
Depression symptoms
Social
disability
Institutionalization
Poor subjective health
n=108; 22-year follow up of >5000 participants in the Framingham study, including patients with AF, cardiac failure, coronary heart disease and hypertension; ADL = activities of daily living; BI = Barthel Index
Kelly-Hayes M et al. J Stroke Cerebrovascular Dis 2003;12:119–26

37. AF is associated with poorer functional performance in survivors of ischaemic stroke
Time after ischaemic stroke
Proportion of patients (%) 10 20 30 40 50 60 70 80
Acute phase
3 months
6 months
12 months
Severe impairment of functional performance*
Patients with AF (n=30)
Patients without AF (n=120)
>40-year follow-up of 5070 participants in the Framingham study; *Barthel Index
Lin HJ et al. Stroke 1996;27:1760–4

38. Costs of stroke associated with atrial fibrillation

39. AF-related stroke is a costly medical event
AF-related stroke is more severe and associated with more disability than non-AF stroke
This translates into higher cost of care compared with stroke without AF
Direct medical costs are increased by approximately one third1
Acute hospital stays are longer2
Total inpatient care costs are higher3
1. Bruggenjurgen B et al. Value Health 2007;10:137–43; 2. Jorgensen HS et al. Stroke 1996;27:1765–9; 3. Ghatnekar O & Glader EL. Value Health 2008;11:862–8

40. Post-stroke costs are higher in the presence of AF
Presence of AF increased the cost of post-stroke care in Germany by approximately one third*
Total direct per patient costs up to 1-year post stroke (€1000)
Patients with AF (n=71)
Patients without AF (n=296) 2 4 6 8 10 12 14
P<0.001
*Data analyzed as part of the Berlin Acute Stroke Study
Data from Bruggenjurgen B et al. Value Health 2007;10:137–43

41. Acute hospitalization accounts for the bulk of AF stroke-related costs
Direct cost components up to 1-year post stroke (% of total direct costs)*
Acute hospitalization
46%
12%
Transport 5% 7%
10%
13%
Re-admission
Aids/home modifications
Medication
Inpatient rehabilitation
Visits to a healthcare professional
Outpatient rehabilitation
Nursing care
*Data analyzed as part of the Berlin Acute Stroke Study
Bruggenjurgen B et al. Value Health 2007;10:137–43

42. Inpatient care costs are higher following AF-related stroke
In Sweden, patients with AF had higher inpatient care costs over 3 years than patients without AF (€10192 vs. €9374; P<0.01)*
Time
post-stroke
Inpatient care costs (€)
P value
Patients with AF
Patients without AF
Year 1
€9012
€8447
<0.001
Year 2
€5817
€5893
0.179
Year 3
€5079
€4604
0.128
*Data analyzed as part of Risk-Stroke, the Swedish national quality assessment register for acute stroke
Ghatnekar O & Glader EL. Value Health 2008;11:862–8

43. Stroke severity increases costs
Mean cost per patient over 18 months (€1000)
Stroke severity*
Severe
0–1 2 3
4–5 5 10 15 20 25 30 35 40
Mild
34 809
18 281
Figure reproduced with permission: ©2002, S. Karger AG, Basel
12 323
10 530
Data for 494 consecutive stroke patients in France; *10-day modified Rankin Scale
Spieler JF et al. Cerebrovasc Dis 2002;13:132–41c

44. Stroke prevention in AF: a cost-effective strategy?
Without effective treatment to prevent formation of thrombi, each year nearly 1 in 20 patients with AF will suffer a stroke1
Dedicated intervention to prevent stroke in AF patients has the potential to significantly reduce care costs
Antithrombotic therapy with vitamin K antagonists can reduce the risk for stroke by 64%2
Drug therapies account for only a small proportion of the total costs of AF3
By reducing the risk of stroke, and hence the need for hospitalization, treatment to prevent stroke has the potential to reduce the overall costs of AF
1. Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–57; 2. Goldstein LB et al Circulation 2001;103:163–82; 3. Coyne KS et al. Value Health 2006; 9:348–56

45. Summary

46. Summary AF is a costly condition
Caring for patients with AF costs €6.2 billion in the EU
Stroke is likely to be more severe and more often fatal in patients with AF compared with those without
People with AF who survive stroke have poorer outcomes and increased and persistent disability
Consequently, AF-related stroke is more costly than non-AF stroke
Costs are increased by approximately 30% in AF patients
The main cost driver is inpatient care costs
Interventions to reduce the incidence of stroke in AF have the potential to improve outcomes and reduce total care costs