Transcript AF Rate vs. Rate Control - Tehran Arrhythmia Center

Atrial Fibrillation
Rate or Rhythm
Control
Saeed Oraii MD
Tehran Arrhythmia Clinic
April 2007
Shiraz
“Delirium Cordis”
• First described by Sir William
Harvey in 17th century:
observed chaotic motion of atria in open
chest animal
• Heart rhythm irregularity first
described in 1903 by Hering
• ECG findings described in
1909 by Sir Thomas Lewis:
“irregular or fibrillatory waves and irregular
ventricular response” or “absent atrial
activity with grossly irregular ventricular
response”
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Atrial fibrillation
accounts for 1/3 of all
patient discharges
with arrhythmia as
principal diagnosis
6%
PSVT
6%
PVCs
18%
Unspecified
4%
Atrial
Flutter
9%
SSS
34%
Atrial
Fibrillation
8%
Conduction
Disease
10% VT
3% SCD
Baily D. J Am Coll Cardiol. 1992;19(3):41A.
2% VF
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Incidence and Prevalence
• Prevalence increases with age
– 4.8 % in the 70-79 age group
• Increases to
– 8.8% in the 80-89 age group
• During the next 7-8 years, the number
of people over the age of 80 is
expected to quadruple
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Atrial Fibrillation Demographics by Age
U.S. population
x 1000
Population with AF
x 1000
Population with
atrial fibrillation
30,000
500
400
U.S. population
20,000
300
200
10,000
100
0
0
<5
5- 10- 15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85- 90- >95
9 14 19 24 29 34 39 44 49 54 59 64 69 74 79 84 89 94
Age, yr
Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.
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Projected AF Prevalence:
OLMSTED COUNTY DATA
12% observed increase in AF incidence
between 1980 and 2000
Miyasaka et al, Circulation 2005; 114:119
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Adults With AF (millions)
Projections of AF Prevalence
in the United States
7
5.6
6
4.3
5
5.2
5.4
3.8
4
3
4.8
2.3
2.4
2.7
2.9
3.3
2
1
0
Adapted from Go. JAMA. 2001;285:2370.
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Complications and Prognosis
• 5-fold increase in risk of stroke and
thromboembolism
• Strokes associated with AF are more
severe
• Death: OR 1.5 –1.9
• AF worsens diagnosis in CHD and HF
• Impairment in cognitive function
• Reduced exercise tolerance
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The 10,000 Foot View …
• The prevalence of AF is rapidly increasing
– Aging population
– True increase in incidence
– Lifetime risk of AF at age 40 is 25%
• AF is a progressive disorder
– Cardiac remodeling due to genetic factors, acquired
disease, atrial fibrillation itself
– Up to 25% of initially self-terminating AF will become
chronic in 5 years, > 50% at 10 years
• Associated with substantial risk of adverse outcomes beyond
immediate symptoms
– Stroke
– Congestive heart failure
– Death
• Associated with substantial increase in health care costs and
resource utilization
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Therapeutic Approaches to
Atrial Fibrillation
• Anticoagulation
• Rate Control (ventricular response)
–
Pharmacologic
–
Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
•
Catheter ablation
•
Surgery (maze)
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Thromboembolic prophylaxis
• Thromboembolic events do not just occur in
permanent AF
• Consider treatment for all patients with AF
• Clustering of events at the time of onset
• 62% RR reduction with adjusted dose
Warfarin
• 22% RR reduction with Aspirin
• 0.9% absolute risk increase of major
haemorrhage with Warfarin
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Risk Assessment Tools
• Do not apply to valvular heart disease
• Risk of thromboembolism depends on
other risk factors in patients with AF
• Various risk assessment tools available
• There are differences between CHAD2
and the tool favoured in the NICE
guidelines
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CHAD2 Score
CHAD2 risk assessment tool
C
H
A
D
2
Congestive heart failure
History of hypertension
Age > 75years
Diabetes
Prior stroke or TIA
CHAD 2
Score
1
1
1
1
2
Adjusted Annual
Stroke Rate (%)
NNT
0
1
1.9
2.8
80
55
2
3
4
5
6
4.0
5.9
8.5
12.5
18.2
38
26
18
12
8
PLEASE NOTE
The benefit of Warfarin
outweighs risk when
CHAD2 Score > 2
Risk of major bleed
(per 100 patient years)
Aspirin
Warfarin
1.5
2.2
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Therapeutic Approaches to
Atrial Fibrillation
• Anticoagulation
• Rate Control
–
Pharmacologic
–
Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
•
Catheter ablation
•
Surgery (maze)
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AF: Pharmacologic Rate Control
• Digitalis
• Beta Blockers
• Calcium Channel Blockers (verapamil,
diltiazem)
• Amiodarone (in special settings)
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Atrial Fibrillation: Rate Control
• Essential in all patients
• Persistent tachycardia rates can induce
cardiomyopathy and heart failure
• Occasional follow-up holter monitor to
ascertain rate control
• Target: 60-80 bpm rest
90-115 bpm with exercise
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Adequate Rate Control
• AFFIRM
– Average HR of ≤80 beats/min at rest and either a
maximum of ≤110 bpm during a 6-minute walk or an
average of <100 bpm on 24-hour Holter monitoring,
with the rate not exceeding 110% of maximum
predicted age-adjusted exercise rate.
• RACE
– Resting heart rate on a 12-lead ECG of ≤100
beats/min
• HOT CAFÉ
– A heart rate of 70–90 beats/min on a resting 12-lead
ECG and ≤140 beats/min during moderate exercise
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Digoxin: some words of caution
• Oldest and most commonly prescribed drug
for control of ventricular rate
• Predominant acute effect is mediated by the
autonomic nervous system
• An important slowing effect of the AV node
is mediated by enhanced vagal tone
• Not effective during periods of increased
sympathetic tone
• Not effective in paroxysmal atrial fibrillation
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AVN Ablation and PPM
• Paroxysmal AF –
DDDR pacing with
mode switch
• Permanent AF –
VVIR pacemaker
• Biventricular
devices may be
better in
preserving LV
function
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AVN Ablation and PPM
• Pros:
– Controls and regularizes ventricular rate
– Effective at improving symptoms, QOL and ? LV
function
• Cons:
– Permanent
– Detrimental effects of RV pacing, especially if
reduced LV function already
– Still have thromboembolic risk
– Continue to have loss of atrial contractile function
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Ablate and pace
• Suitable for
– AF with symptomatic rapid ventricular rate
unresponsive to drug Rx, or when drug Rx
not tolerated
– Curative AF ablation not suitable or not
possible
– Patients with a bradycardia indication for
pacing
– More suited to elderly (less requirement
for generator changes and lead revision)
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Therapeutic Approaches to
Atrial Fibrillation
• Anticoagulation
• Rate Control (ventricular response)
–
Pharmacologic
–
Catheter modification/ablation of AV node
• Rhythm Control
– Antiarrhythmic suppression
– Curative procedures
•
Catheter ablation
•
Surgery (maze)
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AF: Rhythm Control Options
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Antiarrhythmic Therapy for Atrial Fibrillation
• Advantages
• Disadvantages
• High efficacy for some
patients, at least
initially
(< 50% of all patients)
• High recurrence rate
• High long-term cost
• Non-curative
• Low initial cost
• Adverse effects
• Noninvasive
• Potential proarrhythmia
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Proarrhythmia
Drug-induced Torsade
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Rhythm vs Rate control Trials
• PIAF
– Lancet 2000
• AFFIRM
– NEJM 2002
• RACE
– NEJM 2002
• STAF
– JACC 2003
• Hot CAFÉ
– Chest 2004
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Rate vs. Rhythm control
• None of the RCTs found rate control inferior
in terms of mortality or quality of life.
• One study showed rate control reduced the
mortality in patients without Heart Failure, in
over 65s and in patients with CHD.
• Reduced rates of hospitalization and adverse
events with rate control
• No difference in the rate of thromboembolic
or hemorrhagic events
• Rate control is more cost effective.
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AFFIRM: Atrial Fibrillation Follow-up Investigation
of Rhythm Management
Design
Multicenter, randomized, open, parallel group
Patients
4060 patients who had atrial fibrillation that was likely to be
recurrent, with other risk factors for stroke or death. Patients with
contraindications for anticoagulant therapy were excluded
Follow up and primary endpoint
Primary endpoint: all-cause mortality. Mean 3.5 years follow up.
Treatment
• Rate control: >1 rate-controlling drugs, plus anticoagulant, or
• Rhythm control: >1 antiarrhythmics, plus cardioversion as
necessary; anticoagulant encouraged but could be discontinued
Nonpharmacological therapies and changes in pharmacological
therapy, including crossover between groups, were permitted.
The AFFIRM Investigators. A comparison of rate control and rhythm control in
patients with atrial fibrillation. N Engl J Med 2002;347:1825–33.
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AFFIRM
Baseline characteristics
Overall
(n=4060)
Rate control
(n=2027)
Rhythm control
(n=2033)
Age (years)a
70
70
70
Female (%)
39
41
38
Predominant cardiac diagnosis (%)
Coronary artery disease
Cardiomyopathy
Hypertension
Valvular disease
Other
No apparent heart disease
26
5
51
5
1
12
25
5
52
5
1
13
28
5
50
5
1
12
23
23
23
History of congestive
heart failure (%)
a
Mean
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
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AFFIRM
Drugs used in rate and rhythm control groupsa
Rate control
Used drug for
initial therapy
No.
(%)
Rhythm control
Used drug
at any time
No.
(%)
Rate control: data available
Digoxin
Beta-blocker
Diltiazem
Verapamil
1957
949
915
583
187
(48.5)
(46.8)
(29.8)
(9.6)
2027
1432
1380
935
340
Rhythm control: data available
Amiodarone
Sotalol
1265
2
1
(0.2)b
(0.1)b
2027
207
84
Used drug for
initial therapy
No.
(%)
(70.6)
(68.1)
(46.1)
(16.8)
1266
417
276
198
56
(10.2)
(4.1)
1960
735
612
Used drug
at any time
No.
(%)
(32.9)
(21.8)
(15.6)
(4.4)
2033
1106
1008
610
204
(54.4)
(49.6)
(30.0)
(10.0)
(37.2)
(31.2)
2033
1277
841
(62.8)
(41.4)
a A few patients in the rate and a significant number in the rhythm control groups received other antiarrhythmics
b These patients immediately crossed over to the rhythm control group, a protocol violation
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
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AFFIRM
Goals of AFFIRM
– Resting HR <80
– 24 hr Holter average <100 bpm. No HR above 110%
of age predicted maximum
– HR <110 on a six min walk
Anticoagulate:
-If over 48hrs of AF, must anticoag before
cardioversion.
-Warfarin (6-12wks), heparin, LMWH
-Aspirin
-If Lone AF aspirin or nothing
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AFFIRM
- RESULTS -
• No significant difference between rate control and
rhythm control groups in:
—all-cause mortality (25.9 vs. 26.7%, P=0.08)
—composite secondary endpoint (death, disabling
stroke or anoxic encephalopathy, major bleeding,
and cardiac arrest)
—total number of central nervous system events
(stroke or hemorrhage)
• Nonsignificant trends were towards reduction of allcause mortality and CNS events with rate control,
compared with rhythm control
• Significantly reduced hospitalization in rate control
group compared with rhythm control
• Fewer patients initially assigned to rate control crossed
over to rhythm control than crossed from rhythm to
rate control (15 vs. 38% at 5 years; P<0.001)
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AFFIRM
- RESULTS -
All-cause mortality
Cumulative
mortality
(%)
30
25
20
15
P=0.08
10
5
Rhythm control
Rate control
0
0
1
2
3
4
5
Years after randomization
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
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AFFIRM
- RESULTS -
Primary and selected secondary endpoints
Overall
(n=4060)
No.
(%)
Primary endpoint:
all-cause mortality
Rate control
(n=2027)
No.
(%)
Rhythm control
(n=2033)
No.
(%)
P
666
(26.3)
310
(25.9)
356
(26.7)
0.08
Secondary endpoint:
death, disabling stroke,
disabling
encephalopathy, major
bleeding, and cardiac arrest
861
(32.3)
416
(32.7)
445
(32.0)
0.33
CNS eventa
211
(8.2)
105
(7.4)
106
(8.9)
0.93
Hospitalization
2594 (76.6)
a Ischemic stroke, or primary intracerebral
or subdural/subarachonoid hemorrhage
1220 (73.0)
1374 (80.1)
<0.001
AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
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AFFIRM
- SUMMARYIn patients who had atrial fibrillation and were at high
risk for stroke or death, comparison of rate and rhythm
control showed:
• No significant difference in all-cause mortality, composite
secondary endpoint (death, disabling stroke, disabling
anoxic encephalopathy, major bleeding, cardiac arrest) or
ischemic stroke
• A nonsignificant trend to reduction of all-cause mortality
and stroke with rate control
• Reduced hospitalization with rate control
Crossover to the other control method was lower in the
rate control group
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RACE Trial
Rate Control vs. Electrical Cardioversion
• 522 patients with persistent atrial fibrillation or atrial
flutter (24 hours-1 year)
• 2 cardioversions within 1 year
• Rate control to HR < 100 bpm and no symptoms
• Rhythm control: Sotalol followed by Flecainide or
Propafenone followed by Amiodarone
• Primary endpoint: cardiovascular death, admission
or CHF, Thromboembolic events, severe bleeding,
pacemaker implantation or severe anti-arrhythmic
side effects
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RACE Study
522 Patients
256 patients – rate control
266 patients – cardioversion
Outcome
Rate
Rhythm
Death/Stroke
17.2%
22.6%
Mortality
7%
6.7%
CHF
3.5%
3.4%
Hypertension Subgroup: Combined Endpoints:
Mortality/thromboembolism/severe complication
Rate
Rhythm
19%
31%
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Rate vs. Pharmacologic Rhythm
control
Favor of rate control
• Persistent AF
• History of AF more than 1
•
•
•
•
•
•
•
year
Less symptomatic
> than 65 years of age
History of HTN
Previous AAD failure
LA > 60 mm
No history of CHF
Patient preference
Favor of rhythm control
•
•
•
•
•
•
•
•
•
Paroxysmal AF
First episode of AF
More Symptomatic
< than 65 years of age
No history HTN
No Previous AAD failure
LA < 60 mm
History CHF
Patient preference
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Who is under-represented in
AFFIRM?
• Young patients
• Paroxysmal atrial fibrillation
• CHF
• Reduced systolic function
• Isolated diastolic dysfunction
• Disabling symptoms of AF
What therapies are under-represented ?
Other (newer?) drugs
Non-pharmacologic therapies
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What AFFIRM Does Not Tell Us?
• Optimal management for patients with
moderate or severe disabling symptoms
related to atrial fibrillation
• Outcome if better tools to maintain sinus
rhythm were available
• Long-term implications of rate vs. rhythm
control (mean duration of follow-up only
3.5 years)
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Nonpharmacological Approaches
to
Atrial Fibrillation
1. Pacemaker therapy
2. Ablation
3. Surgery
Pulmonary Vein Triggers
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Segmental Ablation
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Segmental Ablation
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Circumferential Ablation
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Circumferential Ablation
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Circumferential Ablation
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Randomized Trials of Ablation for PAF
•
STABILE: EHJ 2006 27:216-221; prior
AAD failure; 1 episode/mo 6 mo
duration; included 32% persistent AF;
AAD given to ablation group;
PVI+MI+CTI; blanking 1 mo; HM + 3 mo
daily event montioring; endpoint 30 sec
AF
•
WANZI: JAMA 2005: 293:2634-2640); No
prior AAD; 1 episode/mo 3 mo duration;
PVAI; blanking 2 mo; HM + 1,3 mo event
monitoring; endpoint 15 sec AF. Pilot
study for RAAFT (400 pt trial)
•
JAIS: HRS Scientific Sessions 2006;
Prior AAD failure, 2 episodes/mo 6 mo
duration; PVI+CTI+lines; blanking 3 mo;
HM + symptom diaries; endpoint 3 min
AF or palpitations
ONE YEAR AF-FREE
STABILE (N=137)
WANZI (N=70)
JAIS (N=112)
PAPPONE (N=198)
0
20
40
60
80
100
•
AAD
ABL
PAPPONE: JACC 2006 in press, doi
10:1016. Limited prior AAD; 2 episodes
/mo 6 mo duration;CPVI+CTI+lines;
blanking 6 wks, daily event monitoring;
endpoint 30 sec AF
Major complications in 1-4% of ablation groups
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Can Ablation Improve Survival?
Pappone et al JACC 2003; 42:186-197
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Catheter ABlation Versus ANtiarhythmic
Drug Therapy for Atrial Fibrillation
(CABANA)
• Randomized trial comparing ablation to best drug therapy (rate
or rhythm control)
• Primary endpoint: mortality (powered for 30% mortality reduction
assuming 12% 3 yr mortality in drug group)
• Secondary endpoints:
– Composite (death, disabling stroke, serious bleeding, cardiac arrest)
– Freedom from AF recurrence (irrespective of symptoms)
– Health care costs and resource utilization
– Quality of life
• Planned 3000 pts, 120 enrolling centers
• Pilot phase approved starting late 2006, full study
pending approval
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Catheter ABlation Versus ANtiarhythmic Drug
Therapy for Atrial Fibrillation (CABANA)
•
Enrollment criteria

> age 65, or < 65 with > 1 risk factor for stroke

Eligible for both AF, and at least 2 membrane active drugs or 3
rate control drugs

Paroxysmal (at least 2 episodes in prior 3 mo), persistent or
chronic AF
•
Ablation technique to include PVI + additional procedures
(lines, CFAE, ganglionated plexi)
•
3 month blanking period in both groups (repeat ablation, or
change in AAD permitted). Crossover to ablation in drug
group strongly discouraged
•
Follow-up with holter monitor, daily TTM (2 wks every 6 mo),
and ILR (proposed 750 pt substudy)
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Curative AF ablation
Potential harm
 Death
 Stroke
 Exacerbation of
arrhythmia
(flutters)
 Tamponade /
PV stenosis
 Failure and redo
rate
Potential benefits
 Symptomatic
benefit
 No need for
AADs ?
 Thromboembolic
benefit ?
 Mortality benefit?
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Who Should be Offered Ablation
Here and Now?
Patients with symptomatic, drug refractory atrial fibrillation, should
be judged on an individual basis according to the Ablation Centre’s
experience
Ideally, the patient should satisfy the following criteria:
 A rhythm control strategy is preferred and other
therapeutic options are not as appropriate
 Attempts with at least 1 AAD have failed
 Preferably <70 (certainly <80!)
 Preferably normal heart or mild-moderate structural
heart disease (LVEF>45%?)
 Preferably not a very dilated left atrium
 Prepared to accept risk of stroke (based on patient
factors and institution’s results)
 Prepared to accept failure (based on institution’s
results)
 Prepared to accept need for a re-do procedure (based
on institution’s results)
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Points to remember:
Will need Warfarin 1 month before and
minimum 3 months after procedure
 May require ongoing AA drug Rx
 AFib and LA flutter often occur in first few
months after procedure. True success
should be assessed after 3-6 months
 Permanent AFib may be considered, but
~50% success rate

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Summing up the evidence
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Who could we offer rhythm control to?
P
?
O
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Key Messages
• All patients with AF need thromboembolic risk assessment.
• Rate control will benefit most of our patients but adequate
rate control is necessary.
• Digoxin is not first line drug for rate control
• The plethora of antiarrhythmic drugs currently
available for the treatment of AF is a reflection that
none is wholly satisfactory, each having limited
efficacy combined with poor safety and tolerability.
• Catheter ablation considered a Class 2a indication for
patients with symptomatic persistent or paroxysmal AF
after failure of an initial trial of AAD therapy (AHA/ACC/ESC
2006 Guidelines)
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