Prophylactic Amiodarone for the Prevention of Arrhythmias That Begin Early After Revascularization, Valvular Repair or Replacement - PAPABEAR
The goal of the trial was to evaluate the safety and efficacy of amiodarone therapy compared with placebo for the prevention of postoperative atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery.
Treatment with amiodarone therapy will be associated with a reduction in postoperative AF or AFL after cardiac surgery compared with placebo.
Patients Screened: 1277
Patients Enrolled: 601
Mean Follow Up: One year
Mean Patient Age: Mean age 61.6 years
Patients of any age or gender scheduled for nonemergency CABG and/or valve surgery
History of sustained AF or AFL, rhythm other than sinus, amiodarone therapy within three months, New York Heart Association class IV heart failure, myocardial ischemia in prior two weeks, systolic blood pressure <80 mm Hg, and ongoing antiarrhythmic therapy
AF or AFL sustained >5 minutes that precipitated treatment and occurred on day 0-6 postoperative
AF or AFL characteristics, time to AF or AFL, burden of AF or AFL, and length of hospitalization
Patients scheduled for nonemergent cardiac surgery were randomized in a double-blind manner to amiodarone therapy (10 mg/kg/d given in two doses; n=299) or placebo (n=301). Therapy was to be administered for six days prior to cardiac surgery through six days after surgery.
The mean duration of randomized treatment prior to surgery was 5.6 days in both arms. Amiodarone concentration on the day of surgery was 1.62 µmol/l.
The primary endpoint of AF or AFL occurred less frequently in the amiodarone arm compared with placebo (16.1% vs. 29.5%, hazard ratio 0.52, 95% confidence interval 0.34-0.69, p<0.001). Similar results were seen in the subgroup of patients age <65 years (11.2% vs. 21.1%, p=0.02), age ≥65 (21.7% vs. 41.2%, p<0.001), coronary artery bypass graft (CABG) surgery only (11.3% vs. 23.6%, p=0.002), valve with or without CABG surgery (23.8% vs. 44.1%, p=0.008), with preoperative beta-blocker therapy (15.3% vs. 25.0%, p=0.03), and without beta-blocker therapy (16.3% vs. 35.8%, p<0.001).
In patients who experienced AF, the ventricular response rate was slower in the amiodarone arm versus placebo (105 beats per minute [bpm] vs. 131 bpm, p<0.001). There was no difference between treatment arms in number of AF episodes, AF/AFL burden, or onset day.
Length of hospital stay trended lower in the amiodarone arm (8.2 days vs. 8.9 days, p=0.11). Adverse events requiring treatment withdraw or reduction occurred more frequently in the amiodarone arm (11.4% vs. 5.3%, p=0.008), but there was no difference in serious adverse events or 1 year mortality (2.7% vs. 4.0%, p=0.50).
Among patients undergoing CABG surgery with or without valve surgery, prophylaxis treatment with amiodarone was associated with a reduction in the primary endpoint of postoperative AF/AFL through day six postop compared with placebo. Beta-blocker therapy is the most studied prophylaxis therapy for preventing AF/AFL; however, there are many contraindications in high-risk cardiac surgery patients, and as such, it is not widely used.
Amiodarone may offer another potential therapy to prevent AF/AFL in these patients, a complication that has been associated with hemodynamic deterioration, stroke and thromboembolic events, longer hospital stays, and increased costs.
Mitchell LB, et al. Prophylactic Oral Amiodarone for the Prevention of Arrhythmias That Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: A Randomized Controlled Trial. JAMA. 2005;294:3093-3100.
Presented by Dr. L. Brent Mitchell at the November 2003 American Heart Association Annual Scientific Sessions, Orlando, FL.
Keywords: Stroke, Confidence Intervals, Coronary Artery Bypass, Cost of Illness, Hemodynamics, Atrial Flutter
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