Prophylactic Amiodarone After Heart Surgery
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
This article originally appeared in the February 2006 issue of Clinical Cardiology Alert. It was originally reviewed by the physician editor, Michael H. Crawford, MD, and peer reviewed by Rakesh Mishra, MD, FACC. Dr. Crawford is Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. He is on the speaker's bureau of Pfizer. Dr. Mishra is Assistant Professor of Medicine, Weill Medical College, Cornell University, Assistant Attending Physician, NewYork-Presbyterian Hospital. He reports no relevant financial relationship related to this field of study.
Synopsis: Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and well tolerated.
Source: 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.
Atrial fibrillation remains a common and vexing problem after cardiac surgery. In this report, we find the results of the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair (PAPABEAR) trial. This was a randomized, controlled study of patients undergoing non-emergent CABG surgery and/or valve surgery. Patients scheduled for elective cardiac surgery were randomized to receive amiodarone or matching placebo in a double-blind fashion with stratification for age, type of surgical procedure, and preoperative beta blocker treatment. Treatment with amiodarone or placebo was begun 6 days prior to surgery, and continued through the first 6 days after surgery. The amiodarone dose was 10 mg/kg daily divided into 2 doses. Patients were treated before surgery as outpatients. Continuous telemetry ECG monitoring was then begun during their operation and continued for the subsequent 6 days. The primary outcome event was documentation of an atrial tachyarrhythmia during the first 6 days after surgery. The atrial tachyarrhythmia had to last for 5 minutes or longer, and require treatment by the attending physician.
Over a 4-year period, a total of 601 patients were randomized into the PAPABEAR trial. The groups were well matched. The mean age of the patients was 61.6 years, and 82% were male. Sixty-five percent had CABG surgery only. Thirty-five percent had valve replacement or repair with or without associated bypass surgery.
Postoperative atrial tachyarrhythmias occurred in 48 of 299 amiodarone patients (16.1%) vs 89 out of 302 (29.5%) placebo patients. Among the patients with arrhythmias, atrial fibrillation was observed in 128 patients and atrial flutter in 9. The peak occurrence in both groups was between day 2 and day 5 after surgery. The hazard ratio for atrial arrhythmias on amiodarone vs placebo was 0.52, and the absolute reduction was 13.4%. Similar hazard ratios in favor of amiodarone were observed when patients were stratified by age, type of surgery, and preoperative beta blocker use.
The durations of postoperative intensive care unit stays were equivalent in the amiodarone and placebo groups, with a slight decrease in total post-hospital stay for the amiodarone patients (8.2 vs 8.9 days, P = 0.11). There were 7 deaths in the placebo group vs 5 in the amiodarone group. Sustained ventricular arrhythmias were less common in the amiodarone group than in the placebo group (0.3% vs 2.6%, P = O.04). Adverse events that led to discontinuation of study drug or dosage reduction were more common in the amiodarone group than in the placebo group. The most common reasons for stopping or reducing therapy were: bradycardia requiring temporary pacing (5.7% vs 2.0%), QT prolongation over 650 m/sec (1.3% vs 0%), and rash (1% vs 0%). Other perioperative complications did not differ between the groups. There were no differences in either readmission to the hospital within 6 months or in one year mortality between the 2 groups.
Mitchell and colleagues conclude that perioperative or oral amiodarone is an effective and well tolerated approach for reducing postoperative atrial tachyarrhythmias after cardiac surgery.
The PAPABEAR trial is the largest study reported to date involving the use of perioperative oral amiodarone in patients scheduled for elective cardiac surgery. Prior studies have indicated that beta adrenergic blockers are also effective in reducing postoperative AF. This study shows that oral amiodarone can be safely begun as an outpatient before surgery and can be used with benefit both alone and in addition to beta blockers. Although no significant changes were observed in the duration of hospital stay, there was a trend towards a favorable decrease in length of stay. Also noted were slight decreases in the frequency of ventricular arrhythmia and in postoperative mortality.
Toxicity is always a question with amiodarone. In PAPABEAR, patients with preoperative bradycardia, QT prolongation, thyroid or hepatic disease, and interstitial pulmonary disease were excluded to minimize the potential for toxicity. After these precautions, the major adverse effect reported was the need for temporary pacing after operation. We are not told if this was confined to the early postoperative phase and, could therefore, be easily treated using epicardial pacing wires. If pacing was needed only in the first 24 to 48 hours after operation, as seems likely, this should not be a major problem. If, however, the bradycardia occurred later in the hospital stay, this would prolong ICU admission and probably require insertion of another transvenous temporary pacing wire, increasing costs, and subjecting the patient to an additional procedure. As expected, other adverse events were minor since the course of therapy was quite short.
The outcome of the PAPABEAR trial and earlier studies indicate that there are significant advantages to a short perioperative course of amiodarone in patients undergoing elective cardiac surgery. Routine use of this approach, particularly in patients at high risk for atrial arrhythmias, should be considered by cardiologists and cardiac surgeons.