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Amiodarone for Atrial Fibrillation

Am Fam Physician. 2000 Dec 15;62(12):2685-2686.

Amiodarone is used for the treatment of atrial fibrillation in many European countries but is labeled in the United States only for life-threatening ventricular arrhythmias. Its success in restoring a sinus rhythm has been inconsistent in clinical trials, with success rates ranging from 16 to 92 percent. In addition, concerns exist about the toxicity of amiodarone. Vardas and colleagues performed a prospective, randomized, controlled trial to evaluate the efficacy and safety of amiodarone in the treatment of atrial fibrillation of long or short duration.

The study included 208 consecutive patients 27 to 78 years of age (mean age: 65) who presented to an emergency department or outpatient clinic because of acute or chronic (more than one month) atrial fibrillation. An anticoagulant was given for 21 days if the duration of atrial fibrillation could not be determined or if it had lasted for more than 48 hours.

Of the 208 patients, 108 were randomized to receive amiodarone and 100 to receive placebo. Baseline clinical characteristics were similar in the two groups. Amiodarone was initially administered as a 300-mg intravenous bolus over one hour, followed by a 24-hour infusion in a dose of 20 mg per kg. It was then given orally, 600 mg daily in three divided doses, for one week, followed by 400 mg daily for three weeks. If the patient had not previously received digoxin, digoxin was also administered during the first 24 hours. Anticoagulation was continued for 21 days after cardioversion. Patients were hospitalized for at least the first three days of treatment and were reevaluated after 30 days of therapy. One-dimensional and two-dimensional echocardiography was performed either 24 hours after conversion or at the end of the study.

Within the first hour of the study, 41 (38 percent) of the patients in the amiodarone group and 25 (25 percent) of those in the placebo group converted to a sinus rhythm. By the end of 24 hours, 25 additional patients in the amiodarone group had converted to sinus rhythm, compared with 15 patients in the placebo group. Thus, by the end of the first day, conversion to normal sinus rhythm had occurred in 61.1 percent of the amiodarone group and 40.0 percent of the placebo group. Between the second day and the 30th day, 21 additional patients who received amiodarone converted to sinus rhythm, compared with no patients in the placebo group. In all, 87 (80.5 percent) of the patients who received amiodarone converted to sinus rhythm by the 30th day, compared with 40 (40 percent) of the persons in the placebo group. Compared with patients who did not have successful conversion, those who converted to sinus rhythm had atrial fibrillation of a shorter duration and smaller atria.

Twelve patients who received amiodarone became hypotensive during the infusion and 17 developed phlebitis at the infusion site. Cessation of therapy because of adverse effects was not required in any of the patients.

The authors conclude that amiodarone is a safe and effective method for termination of atrial fibrillation. While the conversion rate was generally high following administration of amiodarone, it fell to a relatively low level in patients with a very large left atrium or with chronic fibrillation. The conversion rate in patients with a large left atrium was 61 percent, and it was 34.6 percent in those with chronic atrial fibrillation. The authors believe amiodarone could be a drug of first choice for atrial fibrillation, unless rapid conversion is needed.

Vardas PE, et al. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation. Chest. June 2000;117:1538–45.

editor's note: This is the most convincing study to date regarding the use of amiodarone for the treatment of atrial fibrillation. One confounder of this study is that all patients were given digoxin, including acutely in some patients. The risk of toxicity, such as cataract formation and pulmonary fibrosis, with long-term amiodarone therapy makes many clinicians hesitant to use this drug on a long-term basis. This study's findings that left atrial size and the duration of atrial fibrillation are predictors of response corroborate the findings of previous studies. This information may be helpful in the face of making the decision to restore sinus rhythm versus maintaining rate control plus anticoagulation. —j.t.k.

 

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