Amiodarone Prophylaxis Reduces Postoperative AF After CABG, Valve Repair

Peggy Peck

November 13, 2003

Nov. 13, 2003 (Orlando) — Results of a placebo-controlled trial from Canadian researchers suggests that a course of oral amiodarone prophylaxis reduces by about half atrial fibrillation (AF) after coronary artery bypass graft (CABG) with or without valve repair.

"The benefit is consistent in all patient groups: young, old, CABG only, and combined CABG/valve surgery patients," reported L. Brent Mitchell, MD, principal investigator for the Prophylactic Amiodarone for Prevention of Arrhythmias that Begin Early After Revascularization (PAPABEAR) study. "Moreover, amiodarone was equally effective among patients taking beta-blockers and those who were not taking beta-blockers." Dr. Mitchell presented the results here at the American Heart Association Scientific Sessions.

The postoperative AF rate in patients who received amiodarone daily for preoperative days, the day of surgery, and for six days after surgery was 16.1% compared with 29.6% in the placebo group (P < .001). Among patients who underwent CABG alone, the AF rate in the amiodarone arm was 10.9% compared with 23.3% in the placebo arm (P = .002). Similarly, amiodarone prophylaxis was associated with a postoperative AF rate of 24.5% among patients who underwent CABG plus valve repair compared with an AF rate of 41.7% for placebo patients who had the combination surgery (P = .006).

Currently, "the most common postoperative complication of surgical revascularization is postoperative atrial fibrillation," Dr. Mitchell said. "Often postoperative rhythm disturbances are benign, but in patients who develop atrial fibrillation there is concern about hemodynamic deterioration, prolonged hospital stay, and stroke." Data from several studies suggest that postoperative AF is associated with about 30% of CABG surgeries, 40% of valve surgeries, and as high as 50% for patients who undergo combined CABG/valve surgery, he said.

"This [postoperative AF] is a very big problem, so this is a very important trial," Timothy Gardner, MD, professor of surgery at the University of Pennsylvania, told Medscape. "Many centers have been experimenting with amiodarone prophylaxis based on anecdotal reports and observations; now we have a study that supports amiodarone use." He noted, however, that "many surgeries are done in an emergent or urgent setting, so we don't have time for preoperative prophylaxis."

Two months ago the University of Pennsylvania initiated a protocol similar to the one used in the PAPABEAR study for all elective CABG and/or valve repair surgeries, Dr. Gardner said. "It is very early in our experience, but so far we have observed a reduction in AF."

A total of 601 patients were randomized in a 1:1 fashion in the PAPABEAR study. Amiodarone was initiated on an outpatient basis at a dose of 10 mg/kg/day for each of the treatment days. The primary outcome was AF of five minutes or longer requiring therapy within the six-day postoperative period. Secondary endpoints were hospital length of stay, AF characteristics, and adverse effects.

In patients younger than 65 years, amiodarone prophylaxis was associated with an AF rate of 11.2% vs. 21.2% in the placebo group (P = .02). In patients aged 65 years or older, amiodarone treatment was associated with an AF rate of 21.7% vs. 41.2% for the placebo group (P = .001).

Patients receiving preoperative beta-blocker therapy who were randomized to amiodarone had an AF rate of 15.3% vs. 25.1% in the placebo arm (P = .03), whereas patients who were not receiving beta-blocker therapy before surgery who were assigned to the amiodarone arm had an AF rate of 16.3% vs. 35.8% (P = .001), Dr. Mitchell said.

There was, however, no significant difference in postoperative complications — other than AF — or postoperative mortality. On average, amiodarone-treated patients were discharged about a half day earlier than patients in the placebo group, but this difference did not reach significance, he said.

AHA Scientific Sessions: Plenary Session XI — Late-Breaking Clinical Trials. Presented Nov. 12, 2003.

Reviewed by Gary D. Vogin, MD