Use of Metoprolol to Maintain Sinus Rhythm After Conversion From Persistent Atrial Fibrillation - METAFER


The goal of this study was to assess the safety and efficacy of metoprolol CR/XL in the reduction of recurrent atrial fibrillation (AF) among patients with a history of persistent AF who were successfully cardioverted to sinus rhythm.


Indirect data exist that the beta-blocking effects of sotalol are important in the maintenance of normal sinus rhythm after cardioversion from AF. It was therefore hypothesized that a beta-blocker would be effective in maintaining normal sinus rhythm after successful cardioversion from persistent AF.

Study Design

Study Design:

Patients Enrolled: 403
Mean Follow Up: Six months
Female: 30

Patient Populations:

Patients were eligible if they had the persistent form of AF that had lasted for a minimum of three days and up to one year. Patients had to be successfully converted to sinus rhythm either by direct current cardioversion or therapy with class 1 antiarrhythmic drugs.


Exclusion criteria included: contraindications to treatment with beta-adrenergic blocking agents (i.e., presence or history of atrioventricular-block II/III, sick sinus syndrome, asthma); chronic oral treatment with amiodarone within six months prior to inclusion; concomitant treatment with any class 1 or 3 antiarrhythmic drug within five half-lives of that drug; cardiac surgery in the previous two months; clinical need for concomitant treatment with beta-blockers; untreated thyroid dysfunction; and a history of paroxysmal AF (i.e., not persistent AF).

Primary Endpoints:

The primary endpoint of the study was to assess the efficacy of metoprolol CR/XL compared with placebo, with respect to the cumulative number of patients relapsing into AF or flutter during a period of six months following cardioversion to sinus rhythm.

Secondary Endpoints:

Secondary objectives were to compare the effects of metoprolol CR/XL and placebo on the ventricular rate in patients with relapse of AF or flutter and to assess the tolerability of metoprolol CR/XL.

Drug/Procedures Used:

After cardioversion of AF, patients were randomized to either long-acting metoprolol (CR/XL) or placebo. The initial dose of metoprolol CR/XL was 100 mg or placebo given once daily. The goal was to increase the dose to 200 mg once daily. However, the dose could be maintained at 100 mg once daily or decreased to 50 mg once daily at the discretion of the investigator.

Concomitant Medications:

The use of concomitant medications was not restricted. However, concomitant therapy with any class 1 or class 3 antiarrhythmic drugs, beta-blockers, or calcium channel blockers was considered an exclusion criterion.

Principal Findings:

The intention-to-treat analysis demonstrated that 118 patients (59.9%) in the placebo group and 96 patients (48.7%) in the metoprolol CR/XL group had recurrent AF or atrial flutter (p=0.005).

In the subset of patients who underwent electrical cardioversion, 106 patients (65.0%) in the placebo group had recurrent AF, compared with 82 patients (50.6%) in the metoprolol CR/XL group (p=0.002).

In patients who had recurrent AF, the median time to relapse was 7.5 days in the placebo group and 13.0 days in the metoprolol CR/XL group (p=0.001).

Patients who had recurrent AF or flutter had a mean heart rate of 107 ± 27 beats per minute (BPM) in the placebo group, compared with 98 ± 23 BPM in the metoprolol CR/XL group (p=0.015). After adjusting for differences in follow-up times between the placebo and metoprolol CR/XL groups, no significant difference was found in the rate of adverse events.


Among patients with persistent AF, metoprolol CR/XL was associated with a reduction in the primary endpoint of recurrent AF after cardioversion to normal sinus rhythm when compared to placebo with a similar safety profile. These findings suggest that metoprolol CR/XL may be a safe and effective treatment for the prevention of recurrent AF after conversion to normal sinus rhythm.


Kuhlkamp V, Schirdewan A, Stangl K, Homberg M, Ploch M, Beck OA. Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2000;36:139-46.

Clinical Topics: Arrhythmias and Clinical EP, EP Basic Science, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Recurrence, Follow-Up Studies, Research Personnel, Electric Countershock, Sotalol, Metoprolol, Atrial Flutter, Treatment Outcome

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