AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management

Purpose To compare the rhythm-control and rate-control strategies for reducing overall mortality in patients with atrial fibrillation. Reference The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:18251833.

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

Design Randomized, multicentre comparison of rate-control and rhythmcontrol treatment strategies. Patients 4060 patients who were aged 65 years old or who had other risk factors for stroke or death. Of these, 70.8% were hypertensive, and 38.2% had coronary heart disease. Follow-up and primary endpoint The primary endpoint was overall mortality, and the mean follow-up was 3.5 years.

AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management - TRIAL DESIGN continued Treatment Patients were assigned to either the rhythm-control or rate-control strategy groups and were allowed to switch groups if necessary. Rhythm-control strategy group Antiarrhythmic drugs as prescribed by the physician, with cardioversion if required. Continuous anticoagulation therapy with warfarin was encouraged but could be stopped after sinus rhythm was maintained for at least 4 days. Rate-control strategy group Beta-blockers, calcium channel blockers (verapamil and diltiazem), or a combination of these drugs, with continuous anticoagulation therapy with warfarin. Other therapeutic considerations If both treatment strategies failed, patients were considered for nonpharmacological therapy.

AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management - TRIAL DESIGN continued Baseline characteristics
Rate control (n=2027) Mean age years Female sex no. (%) Predominant cardiac diagnosis no. (%) Coronary artery disease Hypertension History of congestive heart failure no. (%) Duration of qualifying atrial fibrillation 2 days no. (%) Any pre-randomization failure of an antiarrhythmic drug no. (%) 69.8 823 (40.6) 497 (24.5) 1045 (51.6) 475 (23.4) 1406 (69.4) 364 (18.0) Rhythm control (n=2033) 69.7 771 (37.9) 562 (27.6) 1018 (50.1) 464 (22.8) 1402 (69.0) 349 (17.2)

The AFFIRM Investigators. N Eng J Med 2002;347:18251833.

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

Primary endpoint More deaths occurred in the rhythm-control group than in the rate-control group (hazard ratio, 1.18; 95% confidence interval, 0.991.41; p=0.07). There was no significant statistical difference in mortality rates between the groups. Rate of crossover between groups 549 patients in the rhythm-control group switched to the rate-control group. Of these, a further 61 crossed back to the rhythm-control group by the end of the study. Morality rates in patient sub-populations In comparison with the rate-control strategy, the rhythm-control strategy was associated with higher rates of death in patients who were older, in patients who had coronary artery disease, and in patients without congestive heart failure.

AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management - RESULTS continued Cumulative mortality from any cause in the rhythm-control and rate-control groups
30 25 Cumulative mortality (%) 20 15 p=0.08 10 Rhythm control 5 0 0 1 2 Years No. of deaths Rhythm control Rate control 0 0 80 (4) 78 (4) Number (percent) 175 (9) 257 (13) 148 (7) 210 (11) 314 (18) 275 (16) 352 (24) 306 (21) 3 4 5 Rate control

The AFFIRM Investigators. N Eng J Med 2002;347:18251833.

AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management - RESULTS continued Hazard ratios for death in pre-specified patient sub-populations Variable
Age <65 yr 65 yr Rhythm at randomization Atrial fibrillation Sinus rhythm Type of episode of atrial fibrillation Recurrent First Coronary artery disease No Yes Hypertension No Yes Congestive heart failure No Yes Left ventricular ejection fraction <50% 50% Sex Female Male Duration of atrial fibrillation <2 days 2 days Overall

Hazard ratio Rhythm control better

(n=969) (n=3091) (n=1778) (n=2095) (n=2526) (n=1391) (n=2509) (n=1551) (n=1184) (n=2876) (n=3121) (n=939) (n=788) (n=2244) (n=1594) (n=2466) (n=1251) (n=2808) (n=4060)

Rate control better

1.0 1.7 0.3 The AFFIRM Investigators. N Eng J Med 2002;347:18251833.

AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management - SUMMARY -

Although there was a trend towards increased mortality in the rhythm-control group versus the rate-control group (p=0.08), there was no significant statistical difference in mortality rates between the two strategies. The crossover rate was significantly greater among patients in the rhythm-control strategy group. The rate-control strategy should be considered as the primary approach in managing atrial fibrillation. Continuous anticoagulation therapy is warranted in all patients with atrial fibrillation and risk factors for stroke.