Rate Control vs Rhythm Control In Atrial Fibrillation

Abstract & Commentary

Synopsis: There was no overall benefit to a rhythm control strategy. Therefore, rate control should be considered a primary therapeutic option, and rhythm control, if elected, may be abandoned early if not fully satisfactory.

Source: Wyse DG. N Engl J Med. 2002;347:1825-1833.

The atrial fibrillation follow-up investigation of Rhythm Management (AFFIRM) trial was designed to test the hypothesis that attempts to maintain sinus rhythm with antiarrhythmic drug therapy are beneficial in patients with atrial fibrillation who, because of age or other risk factors, are at risk for stroke or death. The study enrolled 4060 patients with a mean age of 69.7 years. Sixty-one percent were male. Hypertension was primary cardiac diagnosis in 51% of the patients and was reported as a contributing illness by 71%. Twenty-three percent had a history of congestive heart failure. In order to be eligible for the study, patients had to have had at least 6 hours of atrial fibrillation documented within the preceding 6 months. Patients could be in sinus rhythm at the time of randomization because they had either spontaneously reverted to sinus rhythm or had been cardioverted before randomization. In 69% of the patients, the qualifying episode of atrial fibrillation had lasted for 2 days or longer. In 35% of the patients, the qualifying episode was the first documented episode of atrial fibrillation. Most of the patients had normal left ventricular systolic function with 74% of the patients reported to have a normal left ventricular ejection fraction.

After enrollment, patients were randomized either to a strategy that involved AV nodal blocking agents to control rates during either persistent or recurrent atrial fibrillation or antiarrhythmic drugs to restore and/or maintain sinus rhythm. Any available antiarrhythmic could be chosen by the investigator. Chronic warfarin anticoagulation was required in the rate control group. In the rhythm control group, continuing warfarin therapy was recommended, but anticoagulation could be discontinued at the discretion of the investigator if sinus rhythm was maintained by drug therapy. Rate control was assessed at both rest and during activity. The goal was a heart rate no higher than 80 bpm at rest and no higher than 110 bpm during a 6-minute walk test. The major end point of the trial was overall mortality. Secondary end points evaluated included disabling stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest.

In the rate control group, digoxin, beta-blockers, and calcium channel blockers, alone or in combination, could be used for rate control and this was successful in most patients. During the course of the study, only 5.2% of the patients in the rate control group had to undergo atrioventricular junctional ablation. A total of 248 patients crossed over from the rate control to the rhythm control group but one-third of these failed to maintain sinus rhythm and reverted to a rate control strategy by the end of the study. In the rhythm control group, more than two-thirds of the patients were treated with either amiodarone or sotalol. By the end of the study, almost two-thirds of the patients had undergone at least 1 trial with amiodarone. Rhythm maintenance was assessed at periodic intervals. At the 1-, 3-, and 5-year follow-up visits, 82.4%, 73.3%, and 62.6% of the patients were in sinus rhythm, respectively. Electrical cardioversion was required once in 368 patients, twice in 214 patients, and 3 or more times in 187 patients. By the end of the trial, 594 patients assigned to the rhythm control group had crossed over the rate control group. Anticoagulation was well maintained in the rate control group with more than 85% of the patients on warfarin at each follow-up visit. In the rhythm control group, approximately 70% of the patients remained on warfarin throughout the course of the trial.

There was a slight but not statistically significant increase in mortality in the rhythm control group. By the end of the trial, there had been 352 deaths among the 2033 rhythm control patients vs 306 deaths among the 2027 rate control patients. The average duration of follow-up was 3.5 years. There was no difference in the rates of the composite end point of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. The prevalence of ischemic stroke was similar between the 2 groups within an annual rate of approximately 1% per year. Most of these events occurred in patients in whom warfarin had been stopped or in whom the INR was subtherapeutic. Quality of life measurements were similar between the 2 groups. Subgroup analysis did not identify any group that showed a significant benefit from a rhythm control strategy.

Wyse and colleagues conclude that there was no overall benefit to a rhythm control strategy. Therefore, rate control should be considered a primary therapeutic option, and rhythm control, if elected, may be abandoned early if not fully satisfactory. They also concluded that continuous anticoagulation is warranted in all patients with atrial fibrillation and risk factors for stroke even when sinus rhythm appears to be restored and maintained.

Atrial fibrillation is the most common sustained rhythm encountered by clinicians. It is estimated that more than 2 million patients in the United States have paroxysmal or persistent atrial fibrillation. It had long been assumed that a strategy to maintain sinus rhythm should be the preferred approach for the patients. The data presented in the AFFIRM trial, however, do not support this assumption. If patients can either present with minimal symptoms or their symptoms can be made tolerable with rate control strategy, there seems to be no advantage to the rest of the attempts to maintain sinus rhythm. In particular, it appears that even when sinus rhythm is apparently maintained, patients’ risk for stroke remains high if they are not anticoagulated. Therefore, Wyse et al’s conclusion that either rate control or rhythm control strategy is acceptable as long as anticoagulation is continued seems fully justified.

There were many limitations, however, to the AFFIRM trial. Patients with the most severe symptoms in atrial fibrillation were unlikely to be enrolled in the trial. These patients probably failed attempts at symptom management with a rate control strategy and would not have been randomized. However, data from other studies suggest that these patients are also not well managed with a rhythm control strategy since it is in these sicker patients in whom sinus rhythm is the most difficult to maintain. It is also important to note that patients with both paroxysmal and persistent atrial fibrillation could be entered in the trial and that many patients had undergone cardioversion before they were randomized. This resulted in many patients, even in the rate control group, being in sinus rhythm during major portions of the follow-up period. Obviously, if these patients did not have recurrent atrial fibrillation off drugs, it would have been hard to show benefit in them with drug therapy. The study also did not carefully document if atrial fibrillation recurred and what the duration of the episodes were. Only snapshot views of rhythm maintenance were available. Finally, AFFIRM dealt with a population of patients who were either elderly or who had other risk factors for stroke or death. It, therefore, may not be appropriate to apply the results to younger patients who, although they may be at lower risk for stroke or death, may be more highly symptomatic.

The practical consequences of the AFFIRM trial data are very important to clinicians. If a patient presents with atrial fibrillation and either has few symptoms at presentation or can be made symptom-free with simple rate control strategy, then that approach is certainly acceptable. It should not be required to put many elderly patients with only minor symptoms through repeated cardioversions and drug trials that may have an unfavorable risk-benefit ratio.