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Kochiadakis GE, Igoumenidis NE, Solomou MC, et al. Efficacy of amiodarone for the termination of persistent atrial fibrillation. Am J Cardiol 1999; 83:58-61.

Clinical question Is amiodarone superior to placebo for the restoration of sinus rhythm in patients with persistent atrial fibrillation?

Background Chemical cardioversion is very effective for the treatment of atrial fibrillation (AF) lasting less than 48 hours. For AF of greater duration, chemical cardioversion has been shown to have limited value. A Class III anti-arrhythmic drug, amiodarone has been shown in previous studies to have potential efficacy in the treatment of AF of longer duration. In most cases, however, amiodarone was only used when AF was refractory to other agents, and no studies used a placebo control group.

Population studied The study included 67 consecutive adult patients (32 men, 35 women) with a mean age of 64 years. All had AF of greater than 48 hours' duration and presented either to an emergency department or to the authors' clinic. Exclusion criteria included patients with unstable angina, acute myocarditis, acute pericarditis, a recent myocardial infarction, heart surgery in the previous 6 months, severe uncontrolled heart failure (ejection fraction [is less than] 30%), sick sinus syndrome, a history of second- or third-degree atrioventricular block, use of any anti-arrhythmic drug other than digoxin within a period of 5 half-lives of the drug before the study, cardiogenic shock, significant chronic obstructive pulmonary disease, pulmonary embolism, pneumonia, liver or kidney failure, thyroid disease, electrolyte disturbances, pregnancy, or lactation.

Study design and validity This was a prospective randomized single-blind clinical trial. Patients randomized to the amiodarone group received 300 mg intravenously for 1 hour followed by 20 mg per kg for 24 hours. Simultaneously, they were given 600 mg per day orally, 3 times a day for 1 week, followed by 400 mg per day for 3 weeks. Patients in the placebo group received saline and placebo tablets at a similar frequency. All patients were given digoxin if they had not previously received it. Acenocoumarol (warfarin) adjusted to an international normalized ratio of 3 was given to all patients not already taking anticoagulant medication for at least 21 days before cardioversion was attempted. Patients were observed in a coronary care unit or in the cardiology department for the first 72 hours and evaluated in the clinic at 30 days. The mean duration of AF was 58 and 69 days for the placebo and amiodarone groups, respectively. The relatively long duration of AF may have influenced the findings, since the conversion rate for AF of more than 3 days' duration falls dramatically compared with the conversion of AF of shorter duration.[1] Ideally, the study should have been double-blinded to prevent bias in the interpretation of diagnostic findings.

Outcomes measured The primary outcome was conversion to sinus rhythm within the 1-month study period.

Results At the end of the study period, 16 of 33 patients in the amiodarone group (48.5%) and none of the patients in the placebo group converted to sinus rhythm (P [is less than] .001). No patient converted in the first 24 hours. Beta-blockers were added to the treatment regimen to better control the heart rate in 7 patients (3 in the amiodarone group and 4 in the placebo group). Of these, 2 in the amiodarone group converted. No adverse drug effects necessitated discontinuation of amiodarone, and there were no pro-arrhythmic effects. No side effects were observed in the placebo group.

Recommendations for clinical practice This study lends support for the use of amiodarone for the restoration of sinus rhythm among patients with persistent AF. The extent that these findings can be generalized is limited by the above exclusion criteria. Amiodarone has generally been used as the drug of last resort for the treatment of AF. This is in part because of potentially serious side effects, although studies have shown that these side effects are rare. Consistent with these findings, the present study reported no adverse effects that caused discontinuation of the drug. Further studies are warranted that directly compare oral amiodarone with other oral drugs such as flecainide or propranolol, that measure longer-term outcomes, and that define the duration of therapy.
S. L. Noble, PharmD
William H. Replogle, PhD
Sharon R. Dickey, PharmD
University of Mississippi Medical Center


[1.] The National Heart, Lung, and Blood Institute Working Group on Atrial Fibrillation. Atrial fibrillation: current understandings and research imperatives. J Am Coll Cardiol 1993; 22:1830-4.
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Author:Noble, S. L.; Replogle, William H.; Dickey, Sharon R.
Publication:Journal of Family Practice
Geographic Code:1USA
Date:May 1, 1999

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