BACKGROUND: Amiodarone, a class III antiarrhythmic agent, is effective in the conversion of AF to sinus rhythm. It has been used successfully when administered by either intravenous (IV) or high-dose oral routes. No randomized placebo-controlled studies have been done to determine if a single oral dose of amiodarone may work as effectively.
POPULATION STUDIED: Patients older than 18 years were eligible if 4 criteria were met: recent onset AF (<48 hours) that lasted more than 3 hours; ventricular rate >50 beats per minute (bpm) and <150 bpm; hemodynamic stability, defined as systolic blood pressure >95 mm Hg; and a normal serum potassium level. Patients were excluded for the following conditions: history of acute myocardial infarction, acute pulmonary edema, sick sinus syndrome, high-degree atrioventricular block, or stroke. Women with childbearing potential were ineligible. The final study population was 60% men, and the average age was 60 years.
STUDY DESIGN AND VALIDITY: In this randomized placebo-controlled trial, all medications affecting cardiac rhythm and conduction were discontinued before randomization. Patients received either high-dose oral amiodarone (30 mg/kg) or placebo. Electrocardiogram, echocardiogram, and 24-hour Holter monitoring were performed. Blood pressure was measured at frequent regular intervals for 24 hours. In the event of rapid ventricular response rate (100 to 150 bpm) or patient discomfort, patients in the placebo group were given intravenous verapamil, and those in the amiodarone group received saline in a blinded fashion. Electrocardioversion was administered for hemodynamic deterioration.
OUTCOMES MEASURED: The primary outcome was the percentage of patients successfully converted from AF to sinus rhythm at 24 hours. Proarrhythmic events and other adverse drug effects were recorded.
RESULTS: Of the 72 patients enrolled in the study, 10 were excluded from the final analysis because of technical failure or sinus rhythm at the start of Holter monitoring. Eight hours after drug administration more patients in the amiodarone group had converted to sinus rhythm than in the placebo group (50% vs 20%, P <.001; number needed to treat [NNT]=3.3). Amiodarone was also more effective than placebo for conversion to sinus rhythm at 24 hours (87% vs 35%, P <.001; NNT=2.0). There was no difference in the ventricular response rates, heart rates, or blood pressures between the groups. No proarrhythmic events occurred in either group. One patient in the amiodarone group received IV saline because of a rapid ventricular response, and one had a syncopal episode with a valsalva maneuver. One patient in the placebo group had 2 episodes of sinus arrest with syncope. None of the patients required electrocardioversion. Other side effects, such as headache, diarrhea, and nausea, were similar in each group.
A single dose of amiodarone given at 30 mg per kg is effective in converting new-onset AF to sinus rhythm. This dose was safe and well tolerated by patients in this short study. Since the authors did not report the underlying etiology for AF or the presence of symptoms at diagnosis, it is difficult to apply these findings to clinical practice. Because previous studies have reported rates of spontaneous conversion to sinus rhythm of 64% to 70% when the ventricular rate is controlled,1,2 one should carefully weigh the proarrhythmic risk of a class III antiarrhythmic agent against the risk of rate-controlled watchful waiting before administration of amiodarone for AF.