Title of Trial
Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valvular Repair or Replacement (PAPABEAR)

Date and Citation of Primary Publication(s) or References
Preliminary Results Presented by L. Brent Mitchell, MD
Wednesday, November 12, 2003
American Heart Association Scientific Sessions 2003

Purpose of the Trial
The purpose of this study was to evaluate the safety and efficacy of prophylactic amiodarone for the prevention of post-operative atrial fibrillation and atrial flutter in patients undergoing elective cardiac surgery.

Study Category
Atrial Fibrillation. Prospective randomized trial.

Patient Population
Patients undergoing elective cardiac surgery.

Inclusion Criteria
All patients of either sex or any age scheduled for CABG or valve surgery were considered as candidates for enrollment.

Exclusion Criteria
Patients were excluded from the trial if any of the following criteria were met: emergent surgery, absence of sinus rhythm, NYHA class IV heart failure, prior sustained atrial fibrillation or flutter, an MI within the prior 2 weeks, ongoing antiarrhythmic medications, amiodarone in the preceding 3 months, and contraindications to amiodarone use.

Study Design
Upon enrollment patients were randomized to amiodarone at 10mg/kg/day, rounded to the nearest 100 mg divided in two daily doses, or placebo beginning on the day of surgery and continuing for 6 days post-operatively.

Primary Endpoints
The primary endpoint of the study was 5 minutes or greater of atrial fibrillation or flutter that resulted in therapy within the 6 day postoperative period.

Secondary Endpoints
Secondary endpoints were other atrial or ventricular arrhythmias, time to atrial fibrillation or flutter, burden of atrial fibrillation or flutter, adverse reactions to amiodarone, and length of hospitalizations. Patients were stratified by age (greater or less than 65), type of surgery (CABG, valve surgery with or without CABG), and pre-operative beta blocker administration.

 Baseline Characteristics

	Amiodarone (n=299)	Placebo (n=301)	P value
Age (years)	61.2	61.9	0.48
Male (%)	82.6	81.7	0.78
CAD (%)	75.2	74.1	0.43
HTN (%)	52.2	53.2	0.81
DM (%)	25.4	20.6	0.16
CHF (%)	24.7	24.7	0.86
CVA/TIA (%)	9.4	7.3	0.36
COPD (%)	1.3	2.3	0.37

Time to Follow-up
Primary and secondary endpoints were measured on the sixth post-operative day.

Results
The primary endpoint of atrial fibrillation or flutter occurred less often in the amiodarone group when compared to the placebo group (16.1% vs. 29.6%, p<0.001). This advantage was seen in among subgroups stratified by age, type of surgery, or pre-operative beta blocker use.

The ventricular response during atrial fibrillation, if it occurred, was significantly slower in the amiodarone group (105 bpm vs. 131 bpm, p<0.001). Outcomes that were not significantly different among patients who had atrial fibrillation or flutter in the two groups included: mean time to first occurrence of atrial fibrillation or flutter, number of episodes of atrial fibrillation, duration of the longest episode, and total arrhythmia burden.

Study treatment was withdrawn due to adverse events in significantly more patients in the amiodarone group (11.4% vs. 5.3%, p=0.02). Cardiac adverse effects included bradycardia, and QTc prolongation. Non-cardiac adverse effects, such as nausea and rash, did not differ significantly between the two groups. Post-operative complication rates and mortality rates did not differ between the two groups. Significantly more patients in the amiodarone group were discharged by the sixth post-operative day (54.8% vs. 46.2%, p=0.03).

Sponsor
Wyeth-Ayerst supplied amiodarone and placebo

Trial Status: Completed, preliminary report, not published.