AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management

1
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management

• Purpose
• To compare the effects of rhythm control and
  rate control on mortality in patients with atrial
  fibrillation and high risk of stroke or death
• Reference
• The AFFIRM Investigators. A comparison of rate
  control and rhythm control in patients with
  atrial fibrillation. N Engl J Med
  2002347182533.

2
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- TRIAL DESIGN
-

• 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 gt1 rate-controlling drugs, plus
  anticoagulant, or
• Rhythm control gt1 antiarrhythmics, plus
  cardioversion as necessary anticoagulant
  encouraged but could be discontinued
• Nonpharmacological therapies and changes in
  pharmacological therapy, including crossover
  between groups, were permitted

3
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- TRIAL DESIGN
continued -
Baseline characteristics
Overall
(n4060)
a
Age (years)
70
Female ()
39
Predominant cardiac diagnosis ()
Coronary artery disease
26
Cardiomyopathy
5
Hypertension
51
Valvular disease
5
Other
1
No apparent heart disease
12
History of congestive
23
heart failure ()
a
Mean
AFFIRM Investigators.
N Engl J Med
2002
347
1825

33.
4
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- TRIAL DESIGN
continued -
a
Drugs used in rate and rhythm control groups
Rate control
Rhythm control
Used drug for
Used drug
Used drug for
Used drug
initial therapy
at any time
initial therapy
at any time
No.
()
No.
()
No.
()
No.
()
Rate control
data available
1957
2027
1266
2033
Digoxin
949
(48.5)
1432
(70.6)
417
(32.9)
1106
(54.4)
Beta-blocker
915
(46.8)
1380
(68.1)
276
(21.8)
1008
(49.6)
Diltiazem
583
(29.8)
935
(46.1)
198
(15.6)
610
(30.0)
Verapamil
187
(9.6)
340
(16.8)
56
(4.4)
204
(10.0)
Rhythm control
data available
1265
2027
1960
2033
b
Amiodarone
2
(0.2)
207
(10.2)
735
(37.2)
1277
(62.8)
b
Sotalol
1
(0.1)
84
(4.1)
612
(31.2)
841
(41.4)
a
A few patients in the rate and a significant
number in the rhythm control groups received
other antiarrhythmics
AFFIRM Investigators.
N Engl J Med
2002
347
1825

33.
5
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- RESULTS -

• No significant difference between rate control
  and rhythm control groups in
• all-cause mortality (25.9 vs. 26.7, P0.08)
• 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
  all-cause 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
  Plt0.001)

6
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- RESULTS
continued -
All-cause mortality
Cumulative
30
mortality
()
25
20
15
P0.08
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.
7
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- RESULTS
continued -
Primary and selected secondary endpoints
Rhythm control
Rate control
Overall
(n2033)
P
(n2027)
(n4060)
No.
()
No.
()
No.
()
Primary endpoint
all-cause mortality
0.08
310
(25.9)
356
(26.7)
666
(26.3)
Secondary endpoint
0.33
416
(32.7)
445
(32.0)
861
(32.3)
death, disabling stroke,
disabling
encephalopathy, major
bleeding, and cardiac arrest
CNS eventa
0.93
105
(7.4)
106
(8.9)
211
(8.2)
Hospitalization
lt0.001
1220
(73.0)
1374
(80.1)
2594
(76.6)
a Ischemic stroke, or primary intracerebral or
subdural/subarachonoid hemorrhage
AFFIRM Investigators.
N Engl J Med
2002
347
1825

33.
8
AFFIRM Atrial Fibrillation Follow-up
Investigation of Rhythm Management- SUMMARY -

• In 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