New Guidelines and Therapy
for Atrial Fibrillation
Paul Dorian
St Michael’s Hospital
Director, Division of Cardiology
University of Toronto
Honoraria, consulting fees and research support from
sanofi-aventis, Boehriger-Ingleheim, Bayer, BMS, Servier , Pfizer
1
I see a patient with AF:
What Should I Do?
• Figure out why the patient has afib
Careful BP assessment
Physical
Echo (LV function, LA size)
( TSH, sleep study )
• Figure out extent of symptoms/disability
SAF class (0 – 4)
• Calculate stroke risk
CHADS2 score (0 – 5)
• Start with rate control
• Consider referral if pt still symptomatic/disabled
Traditional treatment goals in AF
Thromboembolism
prevention
Rate control
Rhythm control
Partially addressed by
anticoagulants and/or
Antiplatelets - underused
Adequate rate control defined as
achievement of arbitrary heart rate
target at rest and exrecise
AADs ( or ablation) efficacy
defined as “freedom from AF”
AAD: antiarrhythmic drug
Adapted from Fuster V, et al. Eur Heart J 2006;27:1979-2030.
New treatment goals in AF
Reduction of
cardiovascular
morbidity & mortality
Thromboembolism
prevention
Symptom control
Therapy to reduce major morbid
events ( CHF, ischemic events,
stroke, hospitalizations)
More consistent use
of Anticoagulants
Individualized treatmentpatient specific “therapeutic
contract”
History
Establish Severity (including impact on QoL)
Identify Etiology
Identify reversible causes (hyperthyroidism, ventricular pacing, SVT,
exercise)
Identify factors whose treatment could reduce recurrent AF or
improve overall prognosis (i.e. hypertension, sleep apnea, left
ventricular dysfunction)
Identify potential triggers (i.e. alcohol, intensive aerobic training)
Identify potentially heritable causes of AF (particularly in lone AF)
Determine thrombo-embolic risk (e.g. CHADS2 Score)
Determine bleeding risk to guide appropriate anti-thrombotic therapy
Review prior pharmacologic therapy for AF, for efficacy and adverse
effects
Atrial Fibrillation Guidelines
Establish Pattern of Atrial Fibrillation
Newly Diagnosed AF
Paroxysmal
Persistent
Permanent
Atrial Fibrillation Guidelines
Overview of AF Management
AF Detected
Management of
Arrhythmia
Assessment of
Thromboembolic
Risk (CHADS2)
ASA
OAC
Detection and
Treatment of
Precipitating Causes
Rate
Control
No antithrombotic may be appropriate in selected
young patients with no stroke risk factors
Atrial Fibrillation Guidelines
Rhythm
Control
Establish AF Severity
Use to Guide Therapeutic Approach
CCS
SAF Score
Impact on QOL
0
Asymptomatic
1
Minimal effect on QOL
2
Minor effect of QOL
3
Moderate effect on QOL
4
Severe effect on QOL
Dorian et al Can J Cardiol 2006;22:383-386
Atrial Fibrillation Guidelines
« AF control « is not indicative of symptom control
( defined as rate < 80 or rhythm controlled)
Symptom*
At least one symptom*
%
%
AF control
AF not controlled
68.4
55.7
48.5
42.8
41.9
34.5
32.6
27.6
14.6
15.9
17.6
14.0
1.6
AF
control
AF not
controlled
Palpitation
Dyspnea
Fatigue
Lightheadedness/
dizziness
Chest pain
2.3
Syncope
Steg, Alam, Chiang, et al. ESC 2010, Stockholm
*Symptoms last week including the day of the visit according to AF control
Rate or Rhythm Control?
•
•
•
•
How do you decide if you are going to pursue rate or
rhythm control for a patient with AF?
No right or wrong answer
Often, the two are simultaneous:
– Rhythm control requires good rate control when
patient goes back into AF
Need to continuously re-evaluate the strategy as the AF
progresses
– What may have been a good initial strategy may no
longer be warranted
Atrial Fibrillation Guidelines
Principles of Antiarrhythmic Drug
Therapy to Maintain Sinus Rhythm
1.
2.
3.
4.
5.
6.
Treatment is motivated by attempts to reduce AF-related symptoms
Efficacy of antiarrhythmic drugs to maintain sinus rhythm is modest
Clinically successful antiarrhythmic drug therapy may reduce rather than
eliminate recurrence of AF
If one antiarrhythmic drug ‘fails’ a clinically acceptable response may be
achieved with another agent
Drug-induced proarrhythmia or extra-cardiac side-effects are frequent
Safety rather than efficacy considerations should primarily guide the
choice of antiarrhythmic agent
Atrial Fibrillation Guidelines
Recommendations – Rx Goals
We recommend that the goals of ventricular rate
control should be to improve symptoms and
clinical outcomes which are attributable to
excessive ventricular rates
Strong
Recommendation
Low Quality
Evidence
We recommend that the goals of rhythm control
therapy should be to improve patient symptoms
and clinical outcomes, and that these do not
necessarily imply the elimination of all AF
Strong
Recommendation
Moderate Quality
Evidence
Values and Preferences
These recommendations place a high value on the decision of individual patients
to balance relief of symptoms and improvement in QOL and other clinical
outcomes with the potential greater adverse effects of Class I/III antiarrhythmic
drugs compared to rate control therapy.
Atrial Fibrillation Guidelines
CCS 2010 AF guidelines
We recommend that the goals of ventricular rate control
should be to improve symptoms and quality of life which are
attributable to excessive ventricular rates. (Strong
Recommendation, Low Quality Evidence)
We recommend that the goals of rhythm control therapy
should be to improve patient symptoms and clinical
outcomes, and that these do not necessarily imply the
elimination of all AF. (Strong Recommendation, Moderate
Quality Evidence)
Canadian Cardiovascular Society AF guidelines
Can J Cardiol Feb 2011
CCS 2010 AF guidelines
We recommend a rhythm control strategy for patients
with AF or AFL who remain symptomatic with rate
control therapy or in whom rate control therapy is
unlikely to control symptoms. (Strong Recommendation,
Moderate Quality Evidence)
We recommend use of maintenance oral anti-arrhythmic
therapy as first-line treatment for patients with recurrent
AF in whom long-term rhythm control is desired.
(Strong Recommendation, Moderate Quality Evidence)
Canadian Cardiovascular Society AF guidelines
Can J Cardiol Feb 2011
Antiarrhythmic Drug Choices
Normal Ventricular Function
Dronedarone
Flecainide*
Propafenone*
Sotalol
Catheter Ablation
Amiodarone
* Class I agents should be AVOIDED in CAD
They should be combined with an AV-nodal blocking agents
07/12/2011
Canadian Cardiovascular Society AF guidelines
Can J Cardiol in Press Feb 2011
Antiarrhythmic Drug Choices
Abnormal Left Ventricular Function
EF > 35%
EF ≤ 35%
Amiodarone
Amiodarone
Dronedarone**
Sotalol*
Catheter Ablation
* Sotalol should be used with caution with EF 35-40%
Contra-indicated in women >65 yrs taking diuretics
07/12/2011
Canadian Cardiovascular Society
AF guidelines
Can J Cardiol Feb 2011
** Dronedarone increases mortality in permanent AF with CHF
Heart Rate Control in AF Does Not
Predict Clinical Outcomes
AFFIRM Prospective Sub-study (N=680)
Percent of Patients with
CV Hospitalisation
p=0.29
55%
45%
44%
Q3: 79–87
(n=159)
Q4: 88–148
(n=167)
39%
Q1: 44–69
(n=172)
Q2: 70–78
(n=182)
Achieved Heart Rate at Rest (bpm)
Cooper HA, et al. Am J Cardiol. 2004;93:1247-1253.
07/12/2011
Lenient versus strict rate control in patients
with atrial fibrillation: RACE II
Methods:
• 614 patients with permanent AF
• Resting heart rate < 110 bpm (lenient) or < 80 bpm (strict)
• Primary outcome composite of death from all CV causes,
hospitalization for HF, and stroke, systemic
embolism,
bleeding, and life threatening arrhythmic events
Conclusions:
In patients with permanent AF, lenient rate control is as
effective as strict rate control and is easier to achieve.
__________________________________________________________________________________________________________
Van Gelder I, et al. N Engl J Med 2010;10.1056/NEJMoa1001337
Practical Tips
• Aggressive treatment of hypertension may
prevent or reduce recurrences
• Choice of antihypertensive therapy should
favor rate controlling drugs e.g. β-blockers/
CCBs and inhibitors of renin angiotensin
system vs dihydropyridine Ca2+ channel
blockers
• Identify and treat OSA
Atrial Fibrillation Guidelines
Predictive Index for Stroke
CHADS2
Risk Factor
Score
Patients
(n = 1733)
Adjusted Stroke
Rate (%/yr) 95% CI
CHADS2
Score
120
1.9 (1.2 to 3.0)
0
Congestive Heart
Failure
1
Hypertension
1
463
2.8 (2.0 to 3.8)
1
Age ≥ 75
1
523
4.0 (3.1 to 5.1)
2
Diabetes Mellitus
1
337
5.9 (4.6 to 7.3)
3
Stroke/TIA/
Thromboembolism
2
220
8.5 (6.3 to 11.1)
4
65
12.5 (8.2 to 17.5)
5
Maximum Score
6
5
18.2 (10.5 to 27.4)
6
Atrial Fibrillation Guidelines
RCTs of Warfarin for stroke prevention
RRR = 64%
Hart Ann Int Med 1999;131:492
Atrial Fibrillation Guidelines
In theory, theory is as
good as practice.
In practice, it isn’t
Yogi Berra
ACTIVE-W
Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial
Fibrillation Depends on the Quality of International Normalized Ratio
Control Achieved by Centers and Countries as Measured by Time in
Therapeutic Range
Stroke Outcome; TTR= time in therapeutic range
Connolly et al. Circulation 2008; 118:2029-37
New antithrombotic drugs in Phase III trials for
SPAF
Tissue Factor
Collagen
Aspirin
Plasma Clotting
Cascade
Apixaban
Rivaroxaban
DU 176b
ADP
Thromboxane A2
Clopidogrel
Prothrombin
Idraparinux
AT
Dabigatran
Factor
Xa
Conformational
Activation of GPIIb/IIIa
Thrombin
Fibrinogen
Platelet Aggregation
Fibrin
Thrombus
Anticoagulant Therapy for Stroke Prevention
We recommend that patients at low risk of
stroke (CHADS2 = 1) should receive OAC
therapy (either warfarin [INR 2 – 3] or
dabigatran).
Strong
Recommendation
High Quality
Evidence
We suggest, based on individual risk/benefit
considerations, that aspirin is a reasonable
alternative for some.
Conditional
Recommendation
Moderate Quality
Evidence
We recommend that patients at moderate
risk of stroke (CHADS2 ≥ 2) should receive
OAC therapy (either warfarin [INR 2 – 3] or
dabigatran).
Strong
Recommendation
High Quality
Evidence
Values and preferences: These recommendations place relatively greater
weight on the absolute reduction of stroke risk with both warfarin and
dabigatran compared to aspirin and less weight on the absolute increased
risk for major hemorrhage with an oral anticoagulant compared to aspirin.
Atrial Fibrillation Guidelines
Dabigatran vs Warfarin
We suggest, that when OAC therapy is
indicated, most patients should receive
dabigatran in preference to warfarin. In
general, the dose of dabigatran 150 mg po
bid is preferable to a dose of 110 mg po
Conditional
Recommendation
High Quality
Evidence
Values and preferences: This recommendation places a relatively high
value on the greater efficacy of dabigatran over a relatively short time of
follow-up, particularly among patients who have not previously received
an oral anticoagulant, the lower incidence of intracranial hemorrhage and
its ease of use, and less value on the long safety experience with
warfarin.
Atrial Fibrillation Guidelines
ASA for Stroke Prevention
We recommend that patients at very low risk Strong
of stroke (CHADS2 = 0) should receive aspirin Recommendation
(75-325 mg/day).
High Quality
Evidence
We suggest that some young persons with
no standard risk factors for stroke may not
require any antithrombotic therapy.
Strong
Recommendation
High Quality
Evidence
Atrial Fibrillation Guidelines
I see a patient with AF:
What Should I Do?
• Figure out why the patient has afib
Careful BP assessment
Physical
Echo (LV function, LA size)
( TSH, sleep study )
• Figure out extent of symptoms/disability
SAF class (0 – 4)
• Calculate stroke risk
CHADS2 score (0 – 5)
• Start with rate control
• Consider referral if pt still symptomatic/disabled
RATE vs RHYTHM control
SYMPTOM + DISEASE control
Treat the Patient. Not the ECG.