Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial.
BACKGROUND
Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results.


OBJECTIVE
To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups.


METHODS
Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year.


METHODS
Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative beta-blockers.


METHODS
Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day.


RESULTS
Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative beta-blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative beta-blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality.


CONCLUSIONS
Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251706.
Mitchell
L Brent
LB
Libin Cardiovascular Institute of Alberta, Calgary, Alberta. brent.mitchell@calgaryhealthregion.ca
Exner
Derek V
DV
Wyse
D George
DG
Connolly
Carol J
CJ
Prystai
Gregory D
GD
Bayes
Alexander J
AJ
Kidd
William T
WT
Kieser
Teresa
T
Burgess
John J
JJ
Ferland
André
A
MacAdams
Charles L
CL
Maitland
Andrew
A
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D001026:Coronary Artery Bypass / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D000638:Amiodarone