Atrial Fibrillation 2013: clinical relevance, current and future treatment The New ESC Guidelines
Panos Vardas
Prof. of Cardiology, Heraklion University Hospital
Modest consultancy fees/honoraria from Bayer, Boehringer Ingelheim Bristol Myers Squibb Medtronic Menarini Servier
Complete and chaotic disruption of electrical and mechanical function and synchronization of atrial myofibrils for at least 30 sec
• 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
People with AF in the US (millions)
16 14 12 10 8 Projected incidence of AF assuming a continued increase in age-adjusted incidence as evident in 1980–2000
6 4
Projected incidence of AF assuming no further increase in age-adjusted incidence
2 0 2000
2010
2020
2030 Year
Miyasaka Y et al. Circulation 2006;114:119–25
2040
2050
20
Prevalence (%)
Women (n=4053) Men (n=2590)
15
10
5
0
55–59
60–64
65–69
70–74
75–79
80–84
>85
Age (yrs) Prevalence at baseline assessed in 6808 participants in a European population-based study
Heeringa J et al. Eur Heart J 2006;27:949–53
•
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; 2. Friberg J et al. Epidemiology 2003;14:666–72
European Society of Cardiology Guidelines for the Management of Atrial Fibrillation. Europace 2010;12:1360-420
The main cause responsible for the development of AF Microfibrosis
Fibrosis
Trigger activity
Heterogeneous AF Substrate
Atrial stretch Intrapulmonary venous pressure
AF
SR
AF Sirius red
collagen I
collagen III Boldt et al., Heart 2004
Kostin et al. Cardiovasc Research 2002;54:361-379.
• 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 year 4
• 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; 5. Hannon N et al. Cerebrovasc Dis 2010;29:43–9; 6. Atrial fibrillation; available at http://www.americanheart.org/presenter.jhtml?identifier=4451;
• 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 after diagnosis of AF (men)
40 35 30 25 20 15 10 5 9 85 –8
80 –8
4
9 75 –7
74 70 –
9 65 –6
4 60 –6
–5 9 55
–5 4 50
9 45 –4
4
0 40 –4
Incidence of stroke per 1000 person-years
45
Age (yrs) 22-year follow-up of 75 126 men in the Danish National Registry of Patients Frost L et al. Neuroepidemiology 2007;28:109–15
Annual risk of stroke (%)
14
Observed rate of ischaemic stroke1
12
Intermittent AF Sustained AF
10 8 6 4 2 0
Low
Moderate
High
Stroke risk category
The risk of stroke with asymptomatic or paroxysmal AF is comparable to that with permanent AF1,2 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
Relative risk of stroke
3.0
2.0
1.0
0
Prior stroke or TIA
History of diabetes
*Relative risks are based on decades of age
History of hypertension
History of heart failure
Increasing age*
Risk factor
Risk of stroke depends on a range of factors1 Annual stroke rates can vary 20-fold with no vs. multiple risk factors2 1. Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–57; 2. Gage BF et al. JAMA 2001;285:2864–70
Error bars around each point = 95% CI
Gage BF et al. JAMA 2001;285:2864–70
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
Anticoagulation risk stratification Use of novel oral anticoagulants (NOACs) Left atrial appendage occlusion/excision Pharmacological cardioversion (vernakalant) • Oral antiarrhythmic therapy (dronedarone, and short term therapy) • Left atrial catheter ablation • • • •
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
All patients with atrial fibrillation not treated with VKAs in Denmark 1997- 2006
Kaplan-Meier estimate of probability of remaining free of thromboembolism with CHADS2 score 0 and 1. Only patients with CHADS2 scores 0 and 1 were included, and patients were censored at death for causes other than thromboembolism
73 538 fulfilled the study inclusion criteria
Kaplan-Meier estimate of probability of remaining free of thromboembolism with CHA2DS2 score 0 and 1. Only patients with CHA2DS2 scores 0 and 1 were included, and patients were censored at death for causes other than thromboembolism
Olesen JB et al, BMJ 2011;342:d124
Congestive heart failure/ LV dysfunction Hypertension Age > 75 Diabetes mellitus Stroke/TIA/TE Vascular disease (CAD, AoD, PAD) Age 65-74 Sex category (female) Score 0
1 1 2 1 2 1 1 1 –9
Validated in 1084 NVAF patients not on OAC with known TE status at 1 year in Euro Heart Survey OR for stroke if: Female: 2.53 (1.08 – 5.92), p=0.029; Vascular disease: 2.27 (0.94 – 5.46), p=0.063
Lip GYH, et al. Chest 2009
Olesen JB et al. BMJ 2011;342:124
d = pending EMA/FDA approval – prescribing information is awaited European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
Connolly S et al NEJM 2009; Patel M et al NEJM 2011; Granger C et al NEJM 2011
Connolly S et al NEJM 2009; Patel M et al NEJM 2011; Granger C et al NEJM 2011
Connolly S et al NEJM 2009; Patel M et al NEJM 2011; Granger C et al NEJM 2011
ESC Update on the Management of AF: European Heart Journal/EP- Europace 2012
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
ESC Update on the Management of AF: European Heart Journal/EP- Europace 2012
Holmes DR, et al. Lancet 2009;374:534-42
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
* Includes rheumatic valvular AF, hypertrophic cardiomyopathy, etc. ** Antiplatelet therapy with aspirin plus clopidogrel, or – less effectively – aspirin only, may be considered in patients who refuse any OAC
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
• Patients unwilling to take warfarin • New Patients naive to oral anticoagulation • Those with unstable INR, or warfarin
** P≤0.0001 ** P≤0.0001
CRAFT: Dosing was 2+3 mg/kg; data represents % converted at 60 min post last dose; AF duration 3-72 hours ACT I, III & IV: AF <7 days ACT II: Post CABG and valvular AF study; AF duration 3-72 hours
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
Hohnloser SH et al. N Engl J Med. 2009;360:668-78
Connolly S et al. N Engl J Med. 2011;365:2268-76
September 2009 MULTAQ is indicated in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate (see section 5.1). September 2011 MULTAQ is indicated for the maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation (AF). Due to its safety profile (see sections 4.3 and 4.4), Multaq should only be prescribed after alternative treatment options have been considered. MULTAQ should not be given to patients with left ventricular systolic dysfunction or to patients with current or previous episodes of heart failure. Multaq (Dronedarone) SmPC Europe, September 2011
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
Haissaguerre et al.: NEJM 1998
Paroxysmal AF
Persistent AF
Sinus rhythm was present in 46.6% of patients after the initial procedure during a median follow-up period of 4.8 years. After 1.5 procedures stable sinus rhythm was achieved in 79.5% of patients and an additional 13.0% of patients experienced clinical improvement. Kuck KH et al, Circulation 2010
Arrhythmia-free survival rates after a single catheter ablation procedure were 40%, 37%, and 29% at 1, 2, and 5 years Arrhythmia-free survival following the multiple procedures was 87%, 81%, and 63% at 1, 2, and 5 years HaissaguerreM HaissaguerreM et al, JACC 2011
Acute Procedural Success
Acute procedural success is defined as electrical isolation of all pulmonary veins.
One Year Success
One year success is defined as freedom from AF/AFL/AT off antiarrhythmic drug therapy as assessed from the end of the 3 months blanking period to 12 months following the ablation procedure
Long Term Success
Long term success is defined as freedom from AF/AFL/AT recurrences following the 3-month blanking period through a minimum of 36 months follow-up from the date of the ablation procedure in the absence of Class I and III AAD therapy.
Recurrent AF /AFL/AT
is defined as AF/AFL/AT of at least 30 seconds’ duration that is documented by an ECG or device recording system and occurs following catheter ablation. Recurrent AF/AFL/AT may occur within or following the post ablation blanking period.
is defined as a recurrence of atrial fibrillation within three Early Recurrence of AF months of ablation. Episodes of atrial tachycardia or atrial flutter should also be classified as a “recurrence.”
Late recurrence of AF
is defined as a recurrence of atrial fibrillation 12 months or more after AF ablation. Episodes of atrial tachycardia or atrial flutter should also be classified as a “recurrence.”
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253
Circulation 2011;123:e269-367
Circulation 2011;123:e269-367
Calkins H, et al. Heart Rhythm 2007;4:816-61
European Heart Journal 2012 - doi:10.1093/eurheartj/ehs253