The Importance of Rate Control in Atrial Fibrillation

1
The Importance of Rate Control in Atrial
Fibrillation
Paul Dorian, MD St. Michaels Hospital, Toronto
2
Rate Control for AF When? Why? How?

• When is rate control (as contrasted to rhythm
  control) appropriate?
• Why is rate control needed?
• If rate control is selected, what therapies
  should be used?
• What are the appropriate endpoints to judge
  efficacy?

3
Which is better rhythm control or rate
control? Results of PIAF, RACE, STAF, and AFFIRM
Comparing Rate Control vs. Rhythm Control
1. Honloser et al. Lancet 3561789-94, 2000
2. Van Gelder et al. N Engl J
Med 3471834-00, 2002 3. Carlsson et al. J Am
Coll Cardiol 411690-6, 2003 4. AFFIRM
Investigators N Engl J Med 3471825-33, 2002
4
AFFIRM studyFunctional Status and Quality of
Life

• Exercise capacity
• 6-minute walk
• NYHA CHF class
• CCS angina class
• Quality of Life
• SF-36
• Symptom checklist
• Ladder of Life
• Quality of Life Index

No differences between rate and rhythm control
arms
5
Survival in AFFIRM Time dependent Analysis
Epstein et al, Circulation 20041091509
6
Why is rate control indicated?

• - In most patients, high ventricular rates cause
  symptoms
• - In some pts., continuous uninterrupted
  tachycardia leads to LV dysfunction
• - Multiple studies show that LV dysfunction in A
  Fib is reversible when NSR or rate slowing is
  achieved

7
Effect of Regularity and Rate on EF Before and
After AVN Ablation in Afib
RSA Rate Stabilization Algorithm
Verma et al. PACE 1997201057
8
Effect of IV Digoxin vs. IV Diltiazem in Acute
Atrial Fibrillation
Diltiazem 0.6 mg/kg 10 mg/hr
Digoxin 6.5 µg/kg
Heart Rate / min 133 18 111 26 87 26 91 29
Time (min) baseline 30 60 120
EF 39 10 44 16 54 12 50 11
Heart Rate / min 129 18 126 17 122 16 119
24
EF 38 8 36 10 43 9 51 17
Pinter et al., JCVPT 2003817
9
What therapies are available to control
ventricular rate ?

• Digoxin
• Beta Blockers
• Calcium channel blockers ( diltiazem, verapamil)
• AV node ablation and pacing

10
Rate Control Trials of Digoxin Versus Placebo for
Patients with Atrial Fibrillation
Segal J et al, J Fam Practice 200049(1)47
11
Circadian Distribution of Hourly Mean Ventricular
Rate in Patients with CAF, as Influenced by
Various Treatment Regimens
Farshi et al.,JACC 199933304
12
Effects of nadolol on the spontaneous and
exercise-provoked heart rate of patients with
chronic atrial fibrillation receiving stable
dosages of digoxinDiBianco, R., et al., Am.
Heart J. 1984 108 1121

• We conclude that nadolol is a safe and effective
  agent for the control of spontaneous and
  exercise-provoked heart rates in patients with
  chronic atrial fibrillation who are already
  receiving digoxin treatment.
• 20 pts with permanent AF on digoxin
• poorly controlled ventricular rate (average
  92/min)
• nadolol 40, 80, 120 mg titrated as tolerated
• 3 (15) dropped out for intolerable side effects

• No mention of well being or symptoms

13
Randomized Study of CCB vs. Placebo for Rate
Control in Atrial Fibrillation
All patients on Digoxin Placebo, Diltiazem (270
mg) or Verapamil (240 mg)
Placebo 88 14 127 39 179 13 76 21 19.1
0.3
Diltiazem 76 13 136 42 159 21 84 27 19.3
0.7
Verapamil 80 11 137 39 158 23 85 27 19.2
0.8
P value lt 0.001 lt 0.01 lt 0.05 ns
P value lt 0.01 lt 0.01 lt 0.01 ns
Mean 24 hour HR (bpm) Exer. Tolerance (W) HR at
Max. Exer. Work Load at Resp. Gas Exchange
Threshold (W) Max. Perceived Exertion
Borg Scale
Lundstrom T et al, JACC 19901686
14
Analysis of Pharmacological Rate Control Studies
Meta-Analysis By Segal et al., J Fam Prac 2000
No. of Trials 8 5 5 12
Total No. of Patients 389 88 219 197
Effect on HR during exercise Not ? in 4/4
trials ? in 5/5 trials ? in 2/2 trials ? in 9/9
trials
Effect on HR at rest ? in 7/8 trials ? in 5/5
trials ? in 2/2 trials ? in 7/12 trials
Effect on exercise tolerance ? in 2/4 trials ? in
3/4 trials ? in 2/2 trials ? in 3/9 trials
Drug Digoxin Verapamil Diltiazem ?-blockers
Boriani G et al, Drugs 200363(14)1489
15
PIAF Randomized Study of Rate vs. Rhythm
Control (n 252)
At baseline, 72 on Digoxin
RATE Diltiazem 18 - 270 mg / day

• daily Diltiazem doses 226 63 mg / d _at_ 3 mo.
• 234 64 mg / d _at_ 6 mo.
• 234 68 mg / d _at_ 9 mo.

• 5 / 125 received AVN ablation pacing

• 10 reverted to NSR

Any A/E 47 on diltiazem 15 edema, 14
discontinued due to A/E 64 on amiodarone 25
discontinued due to A/E
16
PIAF rate vs rhythm control in persistent AF
-Symptom Improvement with Diltiazem vs amiodarone
Hohnloser et al., Lancet 2000356(9244)1789
17
Improvement in CAEP Exercise Time with AF
Patients Randomized to Rate Control (MED) 82
CCB or AVJ Ablation (HBA)
Levy et al., Heart 200185171
18
How do we assess rate control?

• Resting HR is poorly correlated with activity HR
  and symptoms
• Most quality of life impairment relates to rapid
  rates on activity or exercise

19
Pt. A.F. Afib 24 hr. heart rates
20
AFFIRM Definition of Adequate Ventricular Rate
Control
1. Average heart rate at rest ? 80 beats / minute
AND
2. Either (a) or (b) (a) Heart rate maximum
during 6 min walk ? 110 bpm (b) Average heart
rate on 24hr Holter monitor ? 100
bpm, with no heart rate gt 110 maximum
predicted age-adjusted exercise heart
Olshansky et al.,2004 in press
21
US Trends in Medication Use in Atrial
Fibrillation
Fang MC et al., Arch Intern Med 200416455
22
CANADIAN CARDIOVASCULAR SOCIETY CONSENSUS
CONFERENCE2004ATRIAL FIBRILLATION
23
Pharmacological and Non-pharmacological Methods
for Rate ControlPaul DorianSean Connors
24
Pharmacological and Non-pharmacological Methods
for Rate Control

• Symptoms during AF are due to the rapid and
  irregular rate
• Sustained high rate may induce cardiomyopathy
• Rate control intended to improve symptoms and
  prevent rapid rate
• Rate control may be needed in persistent/permanent
  AF or paroxysmal AF
• Rate control often easy to achieve at rest but
  not with exercise and thus, exercise tolerance
  may not be improved

25
Pharmacological and Non-pharmacological Methods
for Rate ControlRecommendations

• Class I
• 1. Rate control should be undertaken for
  improvement of symptoms as well as control of
  ventricular rate. (C)
• 2. Administer nondihydropyridine calcium channel
  blocking agents (diltiazem, verapamil) or beta
  blocking agents as initial rate slowing therapy
  in active and younger patients. (B)
• 3. Administer beta blocking agents combined with
  digoxin to control ventricular rate in patients
  with heart failure. (C)

26
Pharmacological and Non-pharmacological Methods
for Rate ControlRecommendations

• Class I
• Consider pacemaker implantation and
  atrioventricular nodal ablation for patients with
  persisting symptoms due to rapid or irregular
  ventricular rate, in whom oral drug therapy is
  ineffective or not tolerated. (A)
• 5. In patients with a rapid ventricular rate
  associated with pre-excitation over an accessory
  bypass tract (Wolff-Parkinson-White Syndrome),
  administer intravenous procainamide or ibutilide
  or perform DC cardioversion if unstable. (B)

27
Pharmacological and Non-pharmacological Methods
for Rate ControlRecommendations

• Class IIa
• 1. Assess ventricular rate at rest and during
  exercise and modify target rates depending on
  patients symptoms. (Level of Evidence C)
• 2. Administer digoxin as initial therapy in
  elderly, inactive patients (Level of Evidence C)
  or as adjunctive therapy to calcium channel or
  beta blocking agents in younger and active
  patients. (Level of Evidence C)

28
Treatment Options for Rate Control Based on
Various Conditions
Boriani G et al, Drugs 200363(14)1489
29
Persistent AFIB Rate Control Desired Symptoms
caused by rapid rate
Rate Control Algorithm
Resting ECG
Ventricular Rate gt 80/min
Ventricular Rate lt 80/min
Start/Add Rate Control Therapy
Walk Test or 24 hr Holter
Activity HR gt110 or AVE HR gt100
Resting ECG
Rate gt 80/min
Rate lt 80/min
Start/Add Rate Control Therapy
Drugs to Control Ventricular Rate
Any of Diltiazem, Beta Blockers, Digoxin

• If patient has CAD, LV dysfunction beta
  blockers
• In younger active patients, consider starting
  with Ditiazem
• Use Digoxin as second line agent ADD to CB or
  BB if necessary
• Assess Adverse Effects Reduce dose if adverse
  effects - add/replace with alternate agent