Calgary, AB - The study with one of the better acronyms in recent years, the PAPABEAR study, short for Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early after Revascularization, Valve Replacement, or Repair, is published in the December 27, 2005 issue of the Journal of the American Medical Association [1].

First presented at the American Heart Association 2003 Scientific Sessions in Orlando, FL and reported by heartwire at that time, the PAPABEAR study shows that the use of prophylactic amiodarone therapy reduces the risk of atrial tachyarrhythmias after cardiac surgery. Oral amiodarone was reported safe overall and was also shown to be effective in several patient subgroups, including older patients and patients also receiving beta-blocker therapy.

"The PAPABEAR trial demonstrates that a 13-day perioperative course of oral amiodarone is an effective, possibly safe, well tolerated, and widely applicable therapy for the prevention of postoperative atrial tachyarrhythmia after cardiac surgery," write lead investigator Dr L Brent Mitchell (University of Calgary, AB) and colleagues. "This benefit was associated with a reduction in the probability of perioperative sustained ventricular tachyarrhythmia and with a trend toward a reduction in postoperative hospital stay."

Speaking with heartwire in 2003, Mitchell noted that atrial tachyarrhythmia—usually atrial fibrillation or atrial flutter—is a common complication following cardiac surgery and is associated with hemodynamic deterioration, stroke, other thromboembolic events, a prolongation of hospital stay, and increased costs. Postsurgical atrial fibrillation occurs in about 30% of CABG patients, 40% of valve-surgery patients, and 50% of patients undergoing CABG and valve surgery, said Mitchell.

PAPABEAR investigators randomized 601 patients undergoing CABG surgery with and without valve repair or replacement to receive amiodarone (10 mg/kg per day) or placebo for six preoperative days, the day of surgery, and six postoperative days. The primary outcome measure was the onset of an atrial tachyarrhythmia lasting longer than five minutes and requiring medical therapy within the six-day postoperative time frame.

Treatment with amiodarone reduced the incidence of postoperative atrial tachyarrhythmia 52% compared with patients receiving placebo. The number needed to treat one patient from developing postoperative atrial tachyarrhythmia was 7.5 patients overall. The number needed to treat was even lower in older patients, patients having valve surgery, and patients not receiving concomitant beta-blocker therapy. There was a reported trend toward a shorter hospital stay. Investigators did not report any significant differences between the two study arms with regard to the day of onset or the number, length, or overall burden of atrial-tachyarrhythmia episodes.

Regarding safety, there were significantly more adverse events leading to the withdrawal of therapy in the amiodarone group than in the placebo group, although investigators say none of the excess adverse events were serious. There was no excessive hemodynamic deterioration or respiratory distress with short-term amiodarone therapy, as had been suggested in other case-control studies.

According to the PAPABEAR investigators, with the important reductions in atrial tachyarrhythmia in the prespecified subgroups, the "results may be generalizable to any setting performing cardiac surgery."

In an editorial accompanying the published paper [2], Drs Mihai Podgoreanu and Joseph Mathew (Duke University Medical Center, Durham, NC) address the all-important clinical question: Should physicians routinely administer prophylactic amiodarone to preoperative surgery patients? This question, write the editorialists, can only be answered by balancing the benefits of therapy against the adverse effects. In PAPABEAR, amiodarone was more likely to be withdrawn, largely because of a threefold increase in bradycardia requiring pacing and an increase in QTc interval prolongation, they note.

The editorialists, who dissected the data, write that there are limited data in the PAPABEAR paper on the interaction between postoperative beta-blocker therapy and amiodarone. Although the guidelines recommend early postoperative beta blockade as standard therapy, "only 50% of cardiac surgical patients are typically treated with beta blockers, and beta blockers are actually withdrawn in 25% of patients," write Podgoreanu and Mathew. It is possible that more patients were withdrawn from beta blockers in the placebo group, exaggerating the observed effect of amiodarone, they write.

The editorialists also note that effective amiodarone prophylaxis appears to require a preoperative treatment period, thus limiting its use to nonemergency settings. "Further large-scale study is needed to determine if surgery should be deliberately delayed for the purpose of prophylaxis against atrial fibrillation in as many patients as possible," write the Duke doctors. Additional study is also needed to define potential genetic modifiers of postoperative atrial fibrillation.

"In the meantime, to help prevent postoperative atrial fibrillation, more widespread use of amiodarone for patients undergoing elective cardiac surgery should be considered," conclude Podgoreanu and Mathew.