Title of Trial
A Comparison of Rate Control and Rhythm Control in Patient with Atrial Fibrillation. The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Investigators.
Date and Citation of Primary Publication(s) or References
Wyse DG. Waldo AL. DiMarco JP. Domanski MJ. Rosenberg Y. Schron EB. Kellen JC. Greene HL. Mickel MC. Dalquist JE. Corley SD. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. New England Journal of Medicine. 347(23):1825-33, 2002 Dec 5
Purpose of the Trial
The purpose of this study was to compare two treatment strategies for atrial fibrillation: cardioversion and maintenance of sinus rhythm with antiarrhythmic drugs and the use of rate controlling drugs while allowing AF to persist.
Study Category
Atrial Fibrillation. Randomized, multicenter trial
Patient Population
Not defined
Inclusion Criteria
To be eligible patients had to be at least 65 years old or have other risk factors for stroke or death. In the clinical judgment of the investigators the criteria, that had to be fulfilled for enrollment, were:
- Atrial fibrillation was likely to be recurrent;
- AF was likely to cause illness or death;
- Long term treatment of AF was warranted;
- Anticoagulation was not contraindicated;
- The patient was able to participate in trials of at least two drugs in both strategies;
- Either treatment strategy could be started after randomization.
Exclusion Criteria
Not defined
Study Design
Patients were randomized to either a rhythm control or rate control strategy. In the rhythm control strategy, antiarrhythmic drugs were chosen by the treating physician and could include amiodarone, disopyramide, flecanide, moricizine, procainamide, propafenone, quinidine, sotalol and a combination of these drugs. Dofetilide was allowed after it became available. Cardioversion could be performed as necessary to restore sinus rhythm. Use of these drugs was guided by a pre-established protocol.
In the rate control strategy, beta-blockers, calcium channel blockers, digoxin or a combination of these drugs could be used to achieve adequate control of the heart rate. The goal for rate control was no greater than 80 bpm at rest and 110 bpm during a six-minute walk test.
Non-pharmacologic approaches to either strategies, such as radiofrequency ablation, pacing, maze procedure etc., could be employed after two attempts at pharmacologic treatment failed.
The goal of oral anticoagulation in both groups was an INR of 2.0-3.0. In the rate control group continuous anticoagulation was mandatory. In the rhythm group anticoagulation therapy was encouraged but could be stop at the treating physician's discretion if sinus rhythm was maintained for a minimum of four weeks.
Primary Endpoint
Overall mortality
Secondary Endpoint
A composite endpoint of death, disabling stroke, disabling anoxic encephalopathy, major bleeding and cardiac arrest
Baseline Characteristics*
| | Overall
(n=4060) | Rate-Control
(n=2027) | Rhythm-Control
(n=2033) |
| Mean age (yrs) | 69.7 | 69.8 | 69.7 |
| Female sex (%) | 39.3 | 40.6 | 37.9 |
| Predominant Cardiac Diagnosis | | | |
| CAD (%) | 26.1 | 24.5 | 27.6 |
| Valvular heart disease (%) | 4.9 | 4.8 | 4.9 |
| Hypertension (%) | 50.8 | 51.6 | 50.1 |
| CHF history (%) | 23.1 | 23.4 | 22.8 |
| Mean LVEF (%) | 54.7 | 54.9 | 54.6 |
| Duration of qualifying AF episode>2 days (no) | 69.2 | 69.4 | 69.0 |
*The two groups did not differ significantly in any baseline characteristic. Time to Follow-up
The mean follow up time was 3.5 years with a maximum of 6 years.
Results
There was no statistical difference in the primary endpoint of total mortality between the two groups; 23.8% in the rhythm control group vs. 21.3% in the rate control group (p=0.08). There was no statistical difference in the combined secondary endpoint. At the five year follow up visit 34.6% of the rate control group was in sinus rhythm, and 80% of those in AF had adequate rate control. The prevalence of sinus rhythm was 62.6% in the rhythm control group at five year follow up. There was a significantly greater proportion of patient crossover from the rhythm control group to the rate control group, when compared to the reverse manner, mostly attributable to inability to maintain sinus rhythm or drug intolerance. During the study more than 85% those patients in the rate control group were maintained on coumadin, while in the rhythm control group that number declined to 70% after the first four months but stayed at approximately that level during the remainder of follow up.
There was no difference between the two groups in the rate of central nervous system events. Hospitalization occurred more frequently in the rhythm control group than in the rate control group (80.1% vs 73.0% respectively, p<0.001). Torsades des pointes was more common the rhythm control group (0.5%) than in the rate control group (0.2%) (p=0.007).
Sponsor
National Heart, Lung and Blood Institute
Wyeth-Ayerst Laboratories contributed amiodarone
Trial Status: Completed
