Late Breaking Trials From the ACC Meeting
Conference Coverage
Editor’s Note: The following reports from the annual scientific session of the American College of Cardiology annual meeting held March 17-20, 2002, in Atlanta, Ga., were obtained by handwritten notes, discussions with investigators, and news reports.
AFFIRM and RACE
Two studies were presented in the late breaking clinical Trial sessions comparing rate control vs. rhythm control strategies in patients with atrial fibrillation. Dr. George Wyse from the University of Calgary presented data from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Trial. This study was a multicenter, randomized, open trial. Unlike other trials addressing this question, mortality and stroke were chosen to be the primary end points. Patients were eligible for the trial if they had ECG documented atrial fibrillation of more than 6 hours duration during the previous 6 months. If persistent atrial fibrillation had been present for more than 6 months, the patient had to be cardioverted back to sinus rhythm for at least 24 hours in order to be enrolled. Patients had to be eligible for anticoagulation therapy and had to have risk factors for either stroke or death while in atrial fibrillation. The risk factors used in the study were age older than 65, hypertension, diabetes, congestive heart failure, prior stroke, left atrial enlargement, or decreased ventricular function. Patients did not have to be in atrial fibrillation at the time of randomization. Patients with paroxysmal atrial fibrillation and those who had undergone a cardioversion before randomization could be enrolled. However, after randomization, patients were to be managed either with a rate control strategy or a rhythm control strategy using antiarrhythmic drugs with repeat cardioversions as necessary. The study enrolled 4060 patients between 1995 and 1999. The mean follow-up was 3.5 years. The patients were elderly with a mean age of about 70 years. The most common diagnosis was hypertension, which was present in 71% of the patients. In more than 70% of the patients, the qualifying episode of atrial fibrillation was greater than 2 days in duration. The episode was the first documented occurrence of atrial fibrillation in 36%. Initial therapy in the rate control arm included digoxin, beta-adrenergic blockers, and calcium channel blockers in approximately equal proportions. Many patients received a combination of 2 or more of these agents. In the rhythm control arm, amiodarone was the first drug selected for 39% and sotalol was selected for 33%. Rate control was carefully monitored throughout the trial, and medications were adjusted based on results of heart rates during ECG monitoring or 6 minute walk tests. Over the course of the study, about 5% of patients in the rate control arm went on to atrioventricular junctional ablation and pacing. In the rhythm control arm, 61% of the patients eventually received a trial of amiodarone and 41% of the patients eventually received a trial of sotalol. More than half of the patients had 1 or more cardioversions during follow-up. In the rhythm control arm, 81% of the patients were still in sinus rhythm after 1 year of therapy. However, by 5 years of therapy, the proportion in sinus rhythm had fallen to 61%. Warfarin use was well maintained in the rate control arm. After 1 year, more than 90% of the patients were still receiving warfarin and this fell only slightly during the subsequent years. In the rhythm control arm, warfarin use was encouraged but not required if the investigator thought the patient was maintaining sinus rhythm. Despite this, at 1 year, about 75% of the rhythm control patients were still on warfarin. Crossovers to the alternate strategy were observed in both groups. About 10% of patients in the rate control strategy were crossed over at some point to attempts at rhythm control. Many of these however reverted to rate control strategy after failure to maintain sinus rhythm. More than 30% of patients in the rhythm control arm eventually switched over to a rate control strategy primarily because of failure to maintain sinus rhythm.
The crude death rate was slightly higher in the rhythm control group (17.5% vs 15.1%) but the P value when the survival curves were compared was 0.058. The rate of ischemic stroke was equal in the 2 groups, with many of the strokes in the rhythm control group seen in patients who were not taking warfarin. Bleeding rates were similar in both groups. There were more hospitalizations after randomization in the rhythm control group, presumably due to hospitalizations for changes in drug therapy. Functional status and quality of life were assessed with several standard measures. There were no differences between the rate and rhythm control arms.
They concluded that any presumed benefits of maintaining sinus rhythm were not realized in this trial. Therefore, attempts to maintain sinus rhythm should be limited with a rate control strategy an acceptable, if not preferred, approach.
Drs. Harry Crijns and Isabelle VanGelder from The Netherlands presented the Rate Control vs. Electrical Cardioversion in Persistent Atrial Fibrillation (RACE) trial. This study involved 522 patients with persistent AF. In the rhythm control arm, anticoagulation was not recommended if the patient maintained sinus rhythm for 30 days after the initial cardioversion. The study used a composite end point that included mortality, thromboembolic events, bleeding, and serious drug toxicity. Mortality was approximately equal in the 2 groups. However, there were more total events in the rhythm control group due to excess ischemic strokes and drug toxicity. Patients with a history of hypertension had a higher risk in the rhythm control arm. They concluded that a rate control strategy with anticoagulation was preferred over rhythm control strategy that did not include long-term anticoagulation.
Comment by John P. DiMarco, MD, PhD
These 2 studies provide several important findings. The most important finding in both studies is that atrial fibrillation patients with risk factors for stroke remain at risk despite a rhythm control strategy. This is true even if vigorous efforts to maintain sinus rhythm are made. These strokes are probably due to both symptomatic and asymptomatic episodes of atrial fibrillation that may occur despite antiarrhythmic drug therapy. Therefore, once atrial fibrillation is identified in patients with other risk factors for stroke, anticoagulation should be continued long-term. The AFFIRM data indicate that rate control and rhythm control strategies result in similar long-term outcomes in terms of mortality and functional status. Therefore, a decision in an individual patient should be based on how they respond to whichever therapy is selected.
These 2 studies provide important data for clinicians who manage patients with atrial fibrillation. Anticoagulation should be continued long-term in all patients with significant risk factors. If a patient is able to tolerate either persistent or paroxysmal atrial fibrillation using a rate control strategy, there appears to be little benefit in aggressive attempts to maintain sinus rhythm.
Dr. DiMarco is Professor of Medicine, Division of Cardiology, University of Virginia, Charlettesville.
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