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Cardioversion of Recent-Onset Atrial Fibrillation: Amiodarone vs Placebo and Class 1c Drugs
Abstract & Commentary
Synopsis: Amiodarone is superior to placebo for cardioversion of AF when measured at 24 hours after drug administration.
Source: Chevalier P, et al. J Am Coll Cardiol. 2003;41: 255-262.
The use of amiodarone for maintenance of sinus rhythm in patients with a history of atrial fibrillation is now well established. However, the role of amiodarone for converting recent-onset atrial fibrillation is less well defined. Chevalier and associates did a literature search of all clinical trials dealing with conversion of recent-onset atrial fibrillation with amiodarone. For inclusion, the study had to be a prospective, randomized trial of amiodarone vs placebo or amiodarone vs a class 1c drug. The primary end point analyzed was conversion to sinus rhythm within the first 24 hours but intermediate time points were also analyzed.
Although 79 potentially relevant articles were identified, 69 were excluded for various reasons. Only 10 met the criteria as stated above. Six studies including 595 patients compared amiodarone with placebo. Seven studies including 579 patients compared amiodarone with a class 1c drug. Three included both a placebo and 1c drug comparison. Five of the 6 amiodarone vs placebo studies used intravenous amiodarone and 1 used a single 30 mg/kg oral dose. Studies that used intravenous propafenone used a 2 mg/kg intravenous bolus followed by a second dose of 1 mg/kg or an infusion of 5-10 mg/kg per 24 hours. Oral propafenone when studied was given as a single 600-mg dose. For flecainide, either a 2 mg/kg intravenous bolus or a single 300-mg oral dose was administered.
None of the studies of amiodarone vs placebo reported drug efficacy at 3-5 hours but at 6-8 hours and at 24 hours, amiodarone was more effective than placebo. Overall, 82% of the patients who received amiodarone vs 56% of the patients who received placebo had converted after 24 hours. Class 1c drugs were more effective than amiodarone at the early time points up to 8 hours, but at 24 hours, there was no difference. The overall conversion rate was 66% for amiodarone and 71% for 1c drugs at the 24-hour time point.
Side effects were minor in the trials. Nonsustained ventricular tachycardia was reported in 2 amiodarone patients and in 1 patient given propafenone. Sustained ventricular tachycardia was observed in 1 patient receiving placebo. Four episodes of 1:1 atrial flutter were reported—3 in patients on flecainide and 1 in a placebo patient.
Chevalier et al conclude that amiodarone is superior to placebo for cardioversion of AF when measured at 24 hours after drug administration. Faster initial rates of conversion are noted with 1c agents, but overall efficacy at 24 hours is similar.
Comment by John DiMarco, MD, PhD
Atrial fibrillation of recent onset remains a major clinical problem. Amiodarone has been shown in a number of trials to be the most effective single agent for maintaining sinus rhythm during chronic therapy, but the literature on the effects of amiodarone for converting recent-onset atrial fibrillation have been uncertain. This paper by Chevalier et al suggests to us the optimal ways to use drugs to convert atrial fibrillation. In patients who do not have ischemic heart disease or congestive heart failure, propafenone and flecainide are the initial drugs of choice for both converting atrial fibrillation and maintaining sinus rhythm thereafter. Patient response to these drugs is relatively rapid, and they can be used in the emergency room setting. However, many patients with particularly problematic atrial fibrillation have either ischemic heart disease or congestive heart failure with ventricular dysfunction, both contraindications to therapy with a 1c agent. Intravenous ibutilide, the most effective rapidly acting agent for converting AF, is also associated with a high incidence of side effects in patients with severe left ventricular dysfunction. In these patients, use of amiodarone has the benefit that it not only may convert the patient back to sinus rhythm and avoid the need for cardioversion, but it also may provide effective long-term prophylactic therapy. Even if conversion is not rapid, the ability to cardiovert with intravenous or oral amiodarone is significant. This is particularly important in critically ill patients in intensive care units in whom the expense of intravenous amiodarone can be justified. In the emergency room setting where the goal is still to discharge the patient quickly, amiodarone does not have a rapid enough action to justify its use. Further studies using oral loading regimens in the outpatient or emergency room setting should be performed to further clarify the role of amiodarone in these situations.
Dr. DiMarco is Professor of Medicine Division of Cardiology University of Virginia, Charlottesville.