Five percent of persons older than 65 years experience atrial fibrillation—the most common cardiac arrhythmia requiring medical treatment. Complications associated with atrial fibrillation include congestive heart failure and reduced exercise tolerance. This condition also increases the risk of stroke fourfold in patients not receiving anticoagulation. It is often possible to restore patients with atrial fibrillation to normal sinus rhythm through cardioversion or with medical therapy; however, the arrhythmia recurs within six months in one half of patients. Data from several small trials have indicated that amiodarone is more effective than other antiarrhythmic agents in treating atrial fibrillation. Roy and colleagues conducted a large, prospective, randomized trial comparing amiodarone with sotalol and propafenone in the prevention of recurrent atrial fibrillation.
Patients were enrolled from 19 centers in Canada. The study subjects were adults who had an episode of symptomatic atrial fibrillation in the past six months for which long-term antiarrhythmic drug therapy was planned. Exclusion criteria included having atrial fibrillation for longer than six months, myocardial infarction during the prior six months, cardiac surgery within 30 days or New York Heart Association class III or IV congestive heart failure.
Patients with atrial fibrillation lasting more than 48 hours were anticoagulated to obtain an International Normalized Ratio of 2 or higher for at least three weeks. They were then randomized to receive amiodarone, sotalol or propafenone in an open-label fashion. Cardioversion was performed in patients who had not converted to sinus rhythm after two weeks of amiodarone therapy or after four days of the other two medications. Patients were seen at three months after randomization, and every six months thereafter. The primary end point was the length of time to a first electrocardiographically confirmed recurrence of atrial fibrillation. Secondary end points were thromboembolic events, death and adverse events caused by the study drugs.
A total of 403 patients were enrolled in the study. There were slightly more men than women, and the mean age for both groups of patients was 65 ± 11 years. During a mean follow-up period of 468 ± 150 days, 71 patients (35 percent) in the amiodarone group had a recurrence of atrial fibrillation compared with 127 patients (63 percent) who were given sotalol or propafenone.
With regard to major clinical events, nine deaths occurred in the amiodarone group and eight deaths in the patients receiving sotalol or propafenone. Eighteen percent of patients in the amiodarone group required treatment for a major clinical event compared with 17 percent in the second group. However, strokes and intracranial hemorrhages were less common in the amiodarone group. Sixty-eight patients in the amiodarone group and 93 patients in the second group stopped taking their medication because of lack of efficacy or adverse events. Four patients who were taking amiodarone had suspected pulmonary toxicity, although it was only proved in one patient. Adverse cardiac events were rare and occurred equally in both study groups.
On the basis of their data, the authors conclude that amiodarone is significantly more effective than sotalol or propafenone in maintaining sinus rhythm in patients with atrial fibrillation. In this study, where the dosage of amiodarone was 200 mg per day, the incidence of adverse events was quite low. The authors suggest that amiodarone should become the drug of choice for use in patients with recurrent atrial fibrillation and structural heart disease.