Epidemiology and burden of atrial fibrillation and associated stroke Module 1

Epidemiology of atrial fibrillation

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

Prevalence of AF predicted to more than double by 2050 8 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

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

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 7.5 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: http://www.decisionresources.com; accessed Feb 2010; 2. Friberg J et al. Epidemiology 2003;14:666–72

Epidemiology of stroke in patients with atrial fibrillation

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 http://cme.medscape.com; accessed Feb 2010; 5. Hannon N et al. Cerebrovasc Dis 2010;29:43–9; 6. Atrial fibrillation; available at http://www.americanheart.org/presenter.jhtml?identifier=4451; accessed 17 Feb 2010

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

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 75 126 men in the Danish National Registry of Patients 10 Frost L et al. Neuroepidemiology 2007;28:109–15 10

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; 2. Flaker GC et al. Am Heart J 2005;149:657–63

Risk factors for stroke in patients with AF

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

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

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

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

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

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

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

Summary

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

The burden and costs of atrial fibrillation

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: 350 000 hospitalizations 276 000 emergency department visits 234 000 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

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

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

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

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

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

The burden of stroke associated with atrial fibrillation

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

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

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

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

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

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

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

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

Costs of stroke associated with atrial fibrillation

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

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

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

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

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

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

Summary

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