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
2002;347:1825–33.
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: >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
AFFIRM: Atrial Fibrillation Follow-up Investigation
of Rhythm Management
- TRIAL DESIGN continued -

Baseline characteristics

Overall Rate control Rhythm control

(n=4060) (n=2027) (n=2033)

Age (years)a 70 70 70
Female (%) 39 41 38
Predominant cardiac diagnosis (%)
Coronary artery disease 26 25 28
Cardiomyopathy 5 5 5
Hypertension 51 52 50
Valvular disease 5 5 5
Other 1 1 1
No apparent heart disease 12 13 12
History of congestive 23 23 23
heart failure (%)

a Mean AFFIRM Investigators. N Engl J Med 2002;347:1825–33.

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

Drugs used in rate and rhythm control groupsa

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
Amiodarone 2 (0.2)b 207 (10.2) 735 (37.2) 1277 (62.8)
Sotalol 1 (0.1)b 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
b These patients immediately crossed over to the rhythm control group, a protocol violation

AFFIRM Investigators. N Engl J Med 2002;347:1825–33.

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%, 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 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; P<0.001)
AFFIRM: Atrial Fibrillation Follow-up Investigation
of Rhythm Management
- RESULTS continued -

All-cause mortality

Cumulative 30
mortality
(%) 25

20

15

10 P=0.08

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.

 AFFIRM: Atrial Fibrillation Follow-up Investigation
of Rhythm Management
- RESULTS continued -

Primary and selected secondary endpoints

Overall Rate control Rhythm control

(n=4060) (n=2027) (n=2033) P
No. (%) No. (%) No. (%)

Primary endpoint:
all-cause mortality 666 (26.3) 310 (25.9) 356 (26.7) 0.08
Secondary endpoint: 861 (32.3) 416 (32.7) 445 (32.0) 0.33
death, disabling stroke,
disabling
encephalopathy, major
bleeding, and cardiac arrest
CNS eventa 211 (8.2) 105 (7.4) 106 (8.9) 0.93
Hospitalization 2594 (76.6) 1220 (73.0) 1374 (80.1) <0.001

a Ischemic stroke, or primary intracerebral

or subdural/subarachonoid hemorrhage AFFIRM Investigators. N Engl J Med 2002;347:1825–33.
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