Rate vs Rhythm Control in Heart Failure Patients
Abstract & Commentary
By John P. DiMarco, MD, PhD Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Source: Roy D, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358: 2667-2677.
The atrial fibrillation and congestive heart Failure (AF-CHF) trial was designed to test the hypothesis that a treatment strategy that involved rhythm control would be superior to rate control in patients with heart failure and left ventricular systolic dysfunction. The study was an international trial conducted in 123 centers throughout the world. Patients were eligible for inclusion if they had a left ventricular ejection fraction of £ 35%, a history of congestive heart failure (New York Heart Association class II to IV), and a history of atrial fibrillation. Patients with persistent atrial fibrillation more than 12 months duration were excluded. Patients were randomly assigned to either a rhythm control strategy or a rate control strategy in an unblinded fashion. Amiodarone, with cardioversions as required, was the primary treatment for maintenance of sinus rhythm. Sotalol or dofetilide were possible alternatives, but were used in only a few patients. The protocol called for a permanent pacemaker to be inserted if bradycardia complicated the use of antiarrhythmic drugs. Rate control therapy included adjusted doses of beta adrenergic blockers with digitalis to achieve a target heart rate of less than 80 bpm at rest and less than 110 bpm during a six-minute walk test. All patients were treated with appropriate heart failure therapy, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, and beta blockers. Anticoagulation was recommended for all patients. Implantable cardioverter defibrillators and ventricular resynchronization therapy were permitted and were used in 7% of both groups. The primary outcome was death from cardiovascular causes. Secondary outcomes were death from any cause, stroke, worsening congestive heart failure, hospitalization, and quality of life.
AF-CHF enrolled 1,376 patients with 682 assigned to a rhythm control strategy and 694 assigned to a rate control strategy. The mean follow-up was 37 ± 19 months, with a maximum follow-up of 74 months. In the entire study group, the mean age was 67 years and 82% of the patients were men. Thirty-one percent of the patients were in New York Heart Association class III or IV. Coronary artery disease was present in 48% of the patients; 48% had systemic hypertension and 21% had diabetes. The mean left ventricular ejection fraction was 27 ± 6%. Atrial fibrillation was persistent in 69% of the patients. During the study, 21% of the patients of the rhythm control group crossed over to the rate control strategy primarily due to an inability to maintain sinus rhythm. In the rate control group, 10% of the patients crossed over to a rhythm control strategy, with worsening heart failure being the most common reason for the change. In the rhythm control group, the prevalence of atrial fibrillation was kept below 20% at each follow-up visit until the 24-month visit and was still only 27% at four years of follow-up. In the rate control group, the presence of atrial fibrillation ranged from 59% to 70% at each follow-up visit. During follow-up, 58% of patients in the rhythm control group had at least one recurrence of atrial fibrillation. In the rate control group, heart rate targets at rest and exercise were achieved in 82% to 88% of the patients during follow-up.
There was no significance in difference in death between the two strategies. Death from cardiovascular causes occurred in 27% of the rhythm control group and 25% of the rate control group. Total deaths were also similar; 32% of the rhythm control group and 33% of the rate control groups died during the course of the study. The annual mortality was almost 10% in both groups. The risks for stroke, worsening heart failure, and the composite endpoint of death from cardiovascular causes, stroke, or worsening heart failure were similar between the two groups. Hospitalization was more common in the rhythm control group than in the rate control group due to hospitalizations for atrial fibrillation or bradyarrhythmias. No significant differences favoring either strategy were noted in any of 10 prespecified subgroups.
Roy et al conclude that the hypothesis of the study that rhythm control would produce benefit in patients with congestive heart failure was not borne out. They suggest that rate control "should be considered a primary approach for patients with atrial fibrillation and congestive heart failure."
Commentary
There have now been seven randomized trials comparing rhythm control and rate control strategies in patients with atrial fibrillation. Six have shown no overall benefit with a rhythm control strategy and the, as yet unpublished, J-RHYTHM study from Japan reported symptomatic improvement only in patients with paroxysmal arrhythmias. The AFFIRM trial enrolled more than 4,000 patients and found no improvement in mortality associated with a rhythm control strategy. In fact, a trend toward increased mortality was noted in the rhythm control group. However, AFFIRM included relatively few patients with advanced heart failure, and many cardiologists have felt that rhythm control would prove to be a superior approach in patients with CHF. The AF-CHF trial was designed to test this hypothesis, but like the other studies, it failed to show an improvement with rhythm control.
There are several possible explanations for this. Although more than three-fourths of patients in AF-CHF assigned to a rhythm control strategy remained in sinus rhythm, the sickest patients may have been the ones with recurrent atrial fibrillation. We should also note that amiodarone, the agent primarily used in AF-CHF, was shown in the Sudden Cardiac Death-Heart Failure Trial to cause a slight increase in mortality among patients with Class III congestive heart failure. Therefore, it is possible that the widespread use of amiodarone in AF-CHF also might have negated any improvement associated with better rhythm control. It also must be noted that an increased cost with a rhythm control strategy, due to the need for more frequent hospitalizations to treat atrial fibrillation and bradyarrhythmias, was seen in AF-CHF and in AFFIRM.
Unless we can develop more effective and safe therapies to prevent atrial fibrillation, rate control should remain a primary option. Patients who do not have moderately severe symptoms related to their atrial fibrillation with a rate control strategy can continue in atrial fibrillation without repeat attempts to restore and maintain sinus rhythm. Although no one argues that atrial fibrillation is a better rhythm than sinus rhythm, the costs of trying to maintain sinus rhythm long-term may not be justified. However, as new antiarrhythmic drugs are developed and catheter ablation techniques for atrial fibrillation improve, we can expect the question of rate control vs rhythm control to continue to be raised.
The atrial fibrillation and congestive heart Failure (AF-CHF) trial was designed to test the hypothesis that a treatment strategy that involved rhythm control would be superior to rate control in patients with heart failure and left ventricular systolic dysfunction.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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