THE IMPORTANCE

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THE IMPORTANCE OF RATE CONTROL IN ATRIAL
FIBRILLATION
L. Brent Mitchell, M.D.
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ATRIAL FIBRILLATION - EPIDEMIOLOGY
The Wave of the Future
US Pop
Feinberg et al Arch Intern Med 155 469, 1995
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ATRIAL FIBRILLATION
Epidemiology Life-Time AF Risk by Age Group
Framingham Heart Study 3997 men / 4726 women
followed 1968 - 2000
Wong et al. Circulation 2002106II-456
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ATRIAL FIBRILLATION
Consequences of Rapid Ventricular Rate

• palpitations
• hemodynamic compromise (dyspnea, angina, others)
• effort intolerance
• de novo congestive cardiomyopathy

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ATRIAL FIBRILLATION - TREATMENT

• Treatment Goals
• identify and correct reversible causes of atrial
  fibrillation
• optimize treatment of cause / underlying
  structural heart disease
• appropriate anticoagulation / antithrombotic
  therapy
• slow ventricular response rate
• consider establishment / maintenance of sinus
  rhythm

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Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM)
AFFIRM Investigators N Engl J Med
20023471825-33
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Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM)
Primary Endpoint - Total Mortality
Rhythm
2033
1932
1807
1316
780
255
Rate
2027
1925
1825
1328
774
236
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RATE CONTROL VS RHYTHM CONTROL IN AF
Completed Trials
Pharmacological Intervention in Atrial
Fibrillation (PIAF) N 252, primary outcome
symptoms RAte Control Versus Electrical
Cardioversion for Persistent Atrial Fibrillation
(RACE) N 531, primary outcome adverse CV
events / bleeding Strategies of Treatment
of Atrial Fibrillation (STAF) N 200, primary
outcome death, arrest, thromboembolism
Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM) N 4060,
all-cause mortality
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Combined Results of PIAF, RACE, STAF, and AFFIRM
Comparing Rate Control versus 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
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ATRIAL FIBRILLATION - TREATMENT

• Therapy to control ventricular response rate
• pharmacological options
• digoxin
• beta adrenoceptor blockers
• centrally-acting calcium antagonists - diltiazem,
  verapamil
• amiodarone
• ablate and pace therapy
• re-establish / maintain normal sinus rhythm

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ATRIAL FIBRILLATION RATE CONTROL
Digoxin for Rate-Control

• advantages
• simple to use
• usually well-tolerated
• once daily therapy
• disadvantages
• ineffective for many at rest
• ineffective for most with exercise

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ATRIAL FIBRILLATION RATE CONTROL
Effectiveness of digoxin therapy
Effectiveness of digoxin therapy not!
12 patients in NSR and 12 patients in AF no,
low, high digoxin levels
AF vs NSR
Controlled vs NSR
beats / min
Although heart rate is reduced...by digoxin,
the heart rate with exercise is not
adequately controlled by any...concentration of
digoxin
The resting heart rate is not a reliable guide
to whether the treatment is adequate.
Beasley et al. BMJ 19852909-11
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ATRIAL FIBRILLATION RATE CONTROL
Beta-Blocker for Rate-Control

• advantages
• usually simple to use
• often well-tolerated
• once daily therapy
• is effective
• disadvantages
• relative-contraindications to beta-blockade
• may decrease exercise tolerance

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ATRIAL FIBRILLATION RATE CONTROL
Effectiveness of nadolol therapy
double-blind crossover comparison of placebo vs
nadolol (N 17)
p lt 0.001 favoring nad
p lt 0.001 favoring nad
p lt 0.01 favoring plac
DiBianco et al. Am Heart J 19841081121-7
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ATRIAL FIBRILLATION RATE CONTROL
Calcium Channel Blocker for Rate-Control

• advantages
• usually simple to use
• often well-tolerated
• once daily therapy
• is effective
• does not decrease exercise tolerance
• disadvantages
• relative-contraindications to calcium blocker
  use

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ATRIAL FIBRILLATION RATE CONTROL
My illegal meta-analysis of placebo-controlled
trials
10 calcium antagonist, 12 beta-blocker, and 8
digoxin trials
p 0.07 favoring CA
p 0.02 disfavoring DIG
p 0.03 favoring CA
with apologies to Segal et al. J Fam Pract
20004947-59
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Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM)
Rate Control Arm
Patients ()
DIG
BB
CA
gt1
AVJAP
CONTROL
AFFIRM Investigators N Engl J Med
20023471825-33
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ATRIAL FIBRILLATION RATE CONTROL
Abate-and-Pace for Rate-Control

• advantages
• essentially always successful
• can discontinue rate-slowing drugs
• does not decrease exercise tolerance
• disadvantages
• requires pacemaker
• relative or absolute pacemaker dependence
• still need anticoagulation / antithrombotic Rx
• risk of torsade de pointes VT if pacemaker
  fails
• small (lt1) mortality?

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ATRIAL FIBRILLATION ABLATE AND PACE
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ATRIAL FIBRILLATION ABLATE AND PACE
A-PACE
HIS
ABLATE
V-PACE
30 RAO
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ATRIAL FIBRILLATION ABLATE AND PACE
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ATRIAL FIBRILLATION ABLATE AND PACE
Mortality Associated with Ablate and Pace
Expected
Mayo Clinic database age-sex matched pop 350 AF
pts with AVJAP 350 AF pts with drugs
N Engl J Med 20013441043-51
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The Three Faces of Atrial Fibrillation
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Happy Face A. Fib Patient

• relatively or absolutely asymptomatic
• tend to be older, sedentary
• usually no hemodynamic compromise

Strategy anticoagulation / antithrombotic
therapy control rate control if necessary - AV
node ablation / pacemaker
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Sad Face A. Fib Patient

• moderate to severely symptomatic
• tend to be younger, more active
• often hemodynamic compromise

Strategy anticoagulation / antithrombotic
therapy informed consent rate-control versus
rhythm control if necessary ablate and pace
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Angry Face A. Fib Patient

• usually severely symptomatic
• tend to be young / no SHD
• often no hemodynamic compromise

Strategy anticoagulation / antithrombotic
therapy informed consent rate-control versus
rhythm control if necessary AF focus ablation
or ablate and pace
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ATRIAL FIBRILLATION RATE CONTROL
Conclusions

• rate-control is a necessary adjunctive
  treatment for A. Fib
• rate-control is a viable primary treatment
  option for A. Fib
• evaluation of rate control requires an exercise
  assessment
• rate control options are digoxin, beta-blocker,
  calcium-blocker
• digoxin is usually ineffective
• beta-blocker best if another indication for
  beta-blockade
• calcium-blocker best if not
• combination therapy is frequently required
• ablate-and-pace approach usually reserved for
  drug failures

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Rate Control Versus Rhythm Control
Reported Randomized Comparisons
Pharmacological Intervention in Atrial
Fibrillation (PIAF) Pilot Study N 252
primary outcome improved symptoms 61 rate
control, 55 rhythm control (p ns) no
difference in quality of life measures rhythm
control - ? 6 minute walk distance, ?
hospitalizations, ? drug AEs Strategies of
Treatment of Atrial Fibrillation (STAF) Pilot
Study N 200 primary outcome cluster of
death, systemic TE, cardiac arrest 10 rate
control, 9 rhythm control (p ns) no
difference in quality of life measures rhythm
control - ? hospitalizations RAte Control versus
Electrical Cardioversion (RACE) N 531 CV
death, CHF hospital, systemic TE, PM, severe
bleed or AE 17 rate control, 23 rhythm control
(p ns) rhythm control - ? CHF, ? bleeding, ?
hospitalizations