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Metoprolol and Cardioversion for Atrial Fibrillation - Metoprolol and Cardioversion for Atrial Fibrillation
Description:
The goal of the trial was to evaluate the effect of metoprolol in combination with repeated cardioversion on maintenance of sinus rhythm among patients with persistent atrial fibrillation (AF).
Study Design
Study Design:
Patients Screened: 615
Patients Enrolled: 168
Mean Follow Up: 6 months
Mean Patient Age: Mean age, 67 years
Female: 29
Patient Populations:
Symptomatic persistent AF with duration of up to 1 year, defined as AF in repeated ECG recordings prior to referral, and confirmed with a 24-hour Holter recording; no history of earlier cardioversion
Exclusions:
Contraindications to treatment with beta-blockers; poorly controlled congestive heart failure; untreated thyroid dysfunction; cardiac surgery in the prior 2 months; absolute indications for beta-blocker treatment such as known coronary artery disease; or treatment with any class I or III antiarrhythmic drug or calcium channel blockers such as verapamil
Primary Endpoints:
Number of patients in sinus rhythm 6 months after the first cardioversion
Secondary Endpoints:
Number of patients with early re-initiation of AF after cardioversion, the number of patients in sinus rhythm at 6 weeks, and the ventricular rates in patients with relapse of AF
Drug/Procedures Used:
Consecutive patients scheduled for direct current cardioversion were randomized in a double-blind manner to metoprolol (n = 83) or placebo (n = 85), with study drug to be taken at least 1 week prior to cardioversion. If a relapse occurred during the first 6 weeks, a second cardioversion was performed.
Concomitant Medications:
All patients were treated with warfarin (international normalized ratio 2.1-3.0) for ≥3 weeks before and through 6 weeks after cardioversion.
Principal Findings:
Mean duration of AF was 5 months. Other than AF, the patients had few comorbidities, including diabetes (7%), chronic obstructive pulmonary disease (6%), or ischemic heart disease (4%). Mean duration of study drug prior to cardioversion was 27 days, with a mean dose of 169 mg in the metoprolol group and 180 mg in the placebo group. Study drug was discontinued prior to cardioversion by four patients in each group; of the four in the metoprolol group, one discontinued due to bradycardia and one due to cerebral hemorrhage that resulted in death. Mean heart rate was lower in the metoprolol group at the time of the first cardioversion (76.1 bpm vs. 88.2 bpm, p < 0.001). Sinus rhythm was not obtained at the time of cardioversion in four patients (5%) in the metoprolol group and six patients (7%) in the placebo group.
Early re-initiation of AF (within 2 hours) occurred in seven patients in the placebo group and none of the metoprolol group (p < 0.01). There was no difference in the need for repeat cardioversion, which was high in both groups (49% of the metoprolol group and 47% of the placebo group, p = 0.8). The primary endpoint of sinus rhythm at 6 months occurred more frequently in the metoprolol group compared with the placebo group (46% vs. 26%, p < 0.01), findings that emerged by 1 week after cardioversion (55% vs. 40%, p = 0.04). Frequency of adverse events was similar between groups.
Interpretation:
Among patients with persistent AF who undergo direct current cardioversion, pretreatment with metoprolol was associated with a higher rate of maintenance of sinus rhythm at 6 months compared with placebo.
Prior small studies have shown beta-blockers had a modest effect in preventing relapse of AF, but the beta-blocker was started after cardioversion. In the present study, the metoprolol was started a mean of 1 month prior to cardioversion, and the difference in sinus rhythm at 6 months was more striking. It should be noted that the 26% rate of sinus rhythm at 6 months in the placebo group was quite low.
Other agents used to maintain sinus rhythm following cardioversion include class I and III antiarrhythmic drugs; however, these agents can also be proarrhythmic. Metoprolol did not appear to be proarrhythmic, although larger studies would be needed to more fully evaluate its safety in this population of patients.
References:
Nergardh AK, Rosenqvist M, Nordlander R, Frick M. Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study. Eur Heart J 2007;28:1351-7.
Keywords: Myocardial Ischemia, Electric Countershock, Comorbidity, Electrocardiography, Heart Rate, Pulmonary Disease, Chronic Obstructive, Recurrence, Bradycardia, Metoprolol, Diabetes Mellitus, Cerebral Hemorrhage
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