Page 27 - Read Online

Waterford et al. Vessel Plus 2022;6:28 https://dx.doi.org/10.20517/2574-1209.2021.115 Page 5 of 12

amiodarone. Second, adding amiodarone to a patient’s home digoxin regimen can increase the level of
digoxin, and dose adjustment of digoxin can be warranted. In fact, levels of digoxin can double in patients
[42]
on amiodarone, and it is recommended to reduce the digoxin dose by 50% in patients on amiodarone .
Third, amiodarone increases the international normalized ratio in patients on warfarin, and warfarin dosing
must be monitored and reduced .
[42]
Clinical trial data on amiodarone
There have been several randomized controlled trials examining oral amiodarone for prophylaxis of POAF
[Table 1]. The first major randomized trial was performed at the University of Michigan in 1997, showing
that amiodarone given 1 week before surgery at a dose of 600 mg daily, then 200 mg daily while in hospital
and none on discharge, reduced the rate of POAF while in hospital from 53% to 25%, and reduced the rate
of POAF after discharge from 12% to 2% . The vast majority of operations were CABG, valve operations,
[43]
or combined CABG-valve operations. 57% had a valve operation of some kind, contributing to a high
baseline rate of POAF in the placebo group. For patients who experienced POAF, the average ventricular
response rate was 112 bpm for the amiodarone group and 135 bpm for the placebo group. This trial was
important for two reasons. First, hospital stay was reduced by 1.4 days in the amiodarone group, and the
cost of hospitalization was reduced from $26,491 to $18,375. This cost reduction does not include the cost of
the increased episodes of POAF after hospital discharge. Second, outpatient initiation of amiodarone proved
safe, with no pro-arrhythmic side effects or serious adverse events such as symptomatic bradycardia.

The PAPABEAR (Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early after
Revascularization, Valve Replacement, or Repair) trial in 2005 randomized 601 patients to placebo or oral
amiodarone (10 mg/kg daily) for 6 days prior to surgery and for 7 days on and after the day of surgery, and
found that the rate of atrial tachyarrhythmias was reduced from 29.5% to 16.1% by amiodarone .
[3]
Postoperative sustained ventricular tachyarrhythmias were less common (0.3% vs. 2.6%). Dosage reduction
of amiodarone was required in 11.4% vs. 5.3% in the placebo group.

The second major randomized trial to examine preoperative oral amiodarone for prevention of POAF was
[44]
the Atrial Fibrillation Suppression Trial (AFIST), published in 2001 . It examined 220 patients who were
receiving beta-blockers preoperatively, and randomized them to receive amiodarone vs. placebo for 1 day
before surgery (if more urgent surgery was required), or for 5 days before surgery. The dose of amiodarone
was 1.6 g for one day or 600 mg daily before surgery if the patients had longer preoperative period.
Amiodarone was then continued on the day of surgery, as well as for 4 days post-operatively. Over 75% of
the patients in the study had an isolated CABG. The rate of POAF was reduced from 38% to 22.5% for
patients in the amiodarone arm, time to the first episode of POAF was lengthened, and the average duration
of POAF episodes was shorter. Rates of bradycardia were not different between amiodarone and placebo.
None of the patients who started amiodarone 5 days before surgery required amiodarone discontinuation
for side effects such as bradycardia, and these patients received amiodarone as well as a beta-blocker.

Other trials have corroborated these results. Another randomized trial of 110 patients undergoing coronary
bypass randomized patients to placebo or amiodarone 600 mg given one day before surgery, and
[45]
amiodarone 600 mg from days 2 to 7 after surgery . Amiodarone was also given in the operating room
(300 mg intravenous), followed by a continuous infusion of a total of 20 mg/kg over the first 24 h after
surgery. Amiodarone was associated with a reduction in POAF (34% vs. 85%), reduction in intensive care
unit stay (1.8 days vs. 2.4 days), and reduction in total hospital stay (11.3 days vs. 13.0 days). This trial also
examined amiodarone levels, defining an effective level as a serum amiodarone level ≥ 0.7 μg/mL and serum
desethylamiodarone level ≥ 0.4 μg/mL. In patients in the amiodarone group who maintained sinus rhythm