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Rhythm Control for Atrial Fibrillation Takes Another Hit

This approach to treatment of patients with heart failure performed poorly in two recent studies.

It is thought that the loss of atrial kick in patients with congestive heart failure contributes to the symptoms — and ultimately the morbidity and mortality — of the condition. Therefore, by inference, maintenance of sinus rhythm should improve heart failure symptoms and mortality. Two research groups have recently examined this hypothesis.

In an international randomized trial, 682 heart failure patients with a history of atrial fibrillation received treatment aimed at achieving sinus rhythm control, and 694 received treatment aimed at achieving a target ventricular heart rate. All participants had LV ejection fractions 35%, and two thirds had persistent, rather than paroxysmal, AF. In the rhythm-control group, 82% of patients received amiodarone, and 2% received sotalol. AF was present in 54% of the rhythm-control patients at baseline and was still markedly prevalent in this group at 3 weeks and 4 months (33% and 17%, respectively). The mean annual rate of cardiovascular death was 8% in both groups (P=0.59). The two groups also had similar risks for stroke; worsening heart failure; and the composite of stroke, worsening heart failure, and death from cardiovascular causes.

In a separate international, randomized, placebo-controlled trial, investigators evaluated the efficacy of dronedarone, a new class-III antiarrhythmic agent similar to amiodarone but without its iodine moiety, in patients with heart failure with or without prior AF or sustained ventricular arrhythmias. The trial was halted early because of significantly increased mortality in the dronedarone group, compared with the placebo group. No significant between-group difference was seen in the incidence of AF.

Comment: Many trials have failed to prove that maintaining normal sinus rhythm improves cardiac hemodynamics and mortality. Whether this failure is attributable to the competing toxicities of the pharmacologic treatment or to a flaw in the logic of the hypothesis is not yet clear. At present, however, sinus rhythm control cannot be recommended for reduction of mortality in patients with or without heart failure. Sinus rhythm control may be a reasonable strategy to treat specific patient complaints that arise directly from AF. Whether sinus rhythm achieved by nonpharmacologic means (i.e., with ablation) can improve mortality in heart failure patients remains to be tested.

— Mark S. Link, MD

Published in Journal Watch Cardiology June 18, 2008

Citation(s):

Roy D et al. for the Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008 Jun 19; 358:2667.

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Køber L et al. for the Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008 Jun 19; 358:2678.

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• Medline abstract (Free)

Cain ME and Curtis AB. Rhythm control in atrial fibrillation — One setback after another. N Engl J Med 2008 Jun 19; 358:2725.

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• Medline abstract (Free)