Metoprolol for preventing relapse in atrial fibrillation?

Zosia Chustecka

July 12, 2000

Wed, 12 Jul 2000 14:34:55

San Francisco, CA - Beta blockers have been an option for managing atrial fibrillation (AF) for many years. They have long been used to control the ventricular response in AF, and recently they have replaced digoxin as a first-line option for AF rate control. So far, however, beta blockers have not been considered to be atrial stabilizing agents except in two well-defined patient populations - those who have recurrent AF associated with stress and anxiety, and those recovering from cardiothoracic surgery (about 30% of whom develop AF).

A group of German researchers headed by Dr Volker K ü hlkamp (Eberhard-Karls-Universität, Tübingen, Germany) suggest that the beta blocker metoprolol "may become the treatment of first choice in patients with atrial fibrillation who require drug therapy to maintain sinus rhythm." They base their comments on a placebo-controlled clinical trial with metoprolol in 394 patients, which they report in the July issue of the Journal of the American College of Cardiology.

However, an accompanying editorial takes issue with these conclusions. In it, Dr Richard Page (Department of Internal Medicine, Cardiovascular Division, Clinical Cardiac Electrophysiology, University of Texas Southwestern Medical Center, Dallas, TX), comments that the German study is an important contribution to the literature on beta blockers in AF, but says that he cannot agree with the suggestion of metoprolol as a first-choice agent.

Metoprolol superior to placebo on relapse

Metoprolol may become the treatment of first choice in patients with atrial fibrillation who require drug therapy to maintain sinus rhythm


The German trial of metoprolol was conducted in patients with a history of persistent AF, who had been successfully converted to sinus rhythm either by direct-current cardioversion or by treatment with Class 1 antiarrhythmic drugs. (The decision as to which was used was left to the discretion of the patient's physician, but cardioversion was recommended.) Metoprolol was used as a long-acting CR/XL formulation (from AstraZeneca, sponsors of the study) at an initial dose of 100 mg once daily, with a recommendation to increase to 200 mg once daily, or decrease to 50 mg once daily if necessary. Concomitant therapy was not restricted, but use of any Class 1 or Class 3 antiarrhythmic agent, beta blockers or calcium channel blockers such as verapamil or gallopamil was considered an exclusion criterion. Patients were followed on an outpatient basis for 6 months, with a resting ECG at every visit, and they were encouraged to come in for an extra ECG if they had symptoms suggestive of a recurrence of AF. However, 9 patients (5 metoprolol, 4 placebo) had only a baseline ECG and were lost to follow-up.

In the metoprolol group (n=197), most patients (62%) stayed on 100 mg once daily, but the dose was reduced to 50 mg once daily in 18.3% and was increased to 200 mg once daily in 16.8%. In the placebo group (n=197), 6.1% had a dose reduction and 25.4% had a dose increase.

Comparison of metoprolol with placebo in AF patients after cardioversion





Relapse into AF

Median time to recurrence

Heart rate

Metoprolol was superior to placebo for preventing relapse into AF or flutter after cardioversion to sinus rhythm, the German group concludes. The reported effects cannot be attributed solely to a better control of the underlying cardiac disease, they comment, because the ability of metoprolol to prevent a relapse to AF was of similar magnitude in all subgroups analyzed (with/without heart failure, hypertension, etc). Also, while direct comparison is difficult, the magnitude of metoprolol's effects appears to be approximately similar to that obtained in studies with class 1 or class 3 antiarrhythmic agents.

Kühlkamp et al note that their findings are in accordance with an observation study published in 1997, which reported a marked reduction of risk for AF if patients were treated with a beta blocker. Finally, they suggest that, because therapy with beta blockers has been shown to be safe, metoprolol may become the treatment of first choice in patients with AF who require drug therapy to maintain sinus rhythm.

Disagreement over metoprolol as first-choice agent

It is with this last statement that Page takes issue in the accompanying editorial, on the basis of two concerns. First, the reduction in recurrence of symptomatic AF with metoprolol is modest - less than the 2-fold increase in median time to recurrence prospectively required for efficacy in other trials. (The FDA's Cardiovascular and Renal Drugs Advisory Committee have recently accepted this assessment of efficacy as providing pivotal data in consideration of labeling for treatment of AF, Page notes). Thus, metoprolol cannot be considered to be an atrial-stabilizing agent in the same league as the commonly used agents, quinidine, disopyramide, propafenone, flecainide, d,l-sotalol and amiodarone, he says. Secondly, when one considers possible asymptomatic AF, it is not clear that metoprolol truly stabilizes the atrium (despite a modest reduction of symptomatic recurrence).


One must keep in mind that this heart rate control may be responsible for reducing the symptoms of AF, making it even more important to continue anticoagulation


However, beta blockers have an excellent safety profile, so reduced efficacy might be acceptable in a first-line agent when the lack of proarrhythmia and serious side effects are considered, Page continues. In addition, beta blockers are a good first choice for controlling ventricular responses in AF, he says, but emphasizes that "one must keep in mind that this heart rate control may be responsible for reducing the symptoms of AF, making it even more important to continue anticoagulation." He adds: "Our group is most comfortable with continuing warfarin therapy indefinitely after cardioversion of AF."

Related links

1. heart wire / Jun 28, 2000 /

2. heart wire / Mar 13, 2000 /


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