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

Table 1. Randomized trials of oral amiodarone as prophylaxis for POAF after cardiac surgery
Number of
Trial (year) Regimen Finding
patients
[43]
Daoud et al. (1997) 124 600 mg amiodarone vs. placebo × 7 days before surgery, then 25% rate of POAF with
200 mg daily vs. placebo until discharge amiodarone vs. 53% with placebo
[3]
Mitchell et al. , 601 Amiodarone 10 mg/kg daily × 13 days, starting 6 days before 16.1% rate of atrial
1
PAPABEAR trial surgery, vs. placebo tachyarrhythmias vs. 29.5% with
(2005) placebo
[44] 2
Giri et al. , AFIST 220 6-7 g total of amiodarone vs. placebo, starting 1 day or 5 days before 22.5% rate of POAF with
3
trial (2001) surgery , given on day of surgery, and given after surgery for 4 days amiodarone vs. 38% with placebo
[45]
Budeus et al. 110 Amiodarone 600 mg one day before surgery, 300 mg IV then 34% rate of POAF with
(2006) 20 mg/kg total dose drip on day of surgery, then 600 mg daily days amiodarone vs. 85% with placebo
2-7 after surgery, vs. placebo
1
Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early after Revascularization, Valve Replacement, or Repair
3
2
(PAPABEAR). Atrial Fibrillation Suppression Trial (AFIST). Timing depended on the clinical requirement for surgery. POAF: Postoperative atrial
fibrillation.
postoperatively, 74% had an effective amiodarone level. By contrast, in the patients in the amiodarone group
who developed atrial fibrillation postoperatively, only 20% had an effective amiodarone level. Of note,
patients with an effective level did not have any difference in baseline characteristics, including body mass
index, compared to patients without an effective level.

Further trials have examined the use of intravenous amiodarone for prophylaxis of POAF [Table 2]. These
trials have either started amiodarone in the operating room, shortly after reaching the intensive care unit, or
on the first postoperative day. A trial published in 1999 consisted of 300 patients randomized to intravenous
amiodarone (1 g/day for 2 days) or placebo, with a continuous amiodarone infusion started within three
hours after reaching the intensive care unit . Compared to oral regimens, this was a low-dose amiodarone
[46]
regimen, and resulted in a more modest reduction in POAF from 47% in the placebo group to 35% in the
amiodarone group (P = 0.01). By contrast, a similar low-dose randomized trial has not shown an effect. In a
trial from 2010, 120 patients undergoing valvular operations were randomized to a loading dose of 300 mg
of intravenous amiodarone in the operating room, followed by an infusion of 15 mg/kg per day for 2
[47]
days . This totals 2.4 g of amiodarone in a 70 kg patient. This trial found that POAF occurred in 59.3% in
the amiodarone group vs. 40% in the placebo group. This article has concluded that a 48 h infusion of
amiodarone does not reduce the rate of POAF after valvular surgery.

Three additional trials, including intravenous amiodarone, used a larger dose and have shown a larger
absolute reduction in POAF. A randomized study from Turkey also demonstrated the value of preoperative
amiodarone . 241 patients scheduled for coronary bypass were randomized to one of three groups.
[48]
Group 1 received 100 mg of metoprolol preoperatively, then 1 mg intravenous digoxin on the day of
operation, then oral digoxin (0.25 mg) and metoprolol (100 mg) postoperatively. Group 2 received a total of
3.45 g of amiodarone, with 1.2 g given intravenously starting on completion of the operation with a 300 mg
bolus, then 450 mg amiodarone the next day intravenously, then 600 mg daily for three days. Group 3
received no antiarrhythmic prophylaxis. The rates of POAF were 16.8% in Group 1, 8.3% in Group 2, and
33.6% in Group 3. Two of 72 patients in Group 2 had amiodarone stopped for atrioventricular block. Next,
a trial from Denmark published in 2007 randomized 250 patients undergoing coronary bypass to
[49]
amiodarone or placebo . Amiodarone was given as 300 mg intravenously over 20 min on the first
postoperative day, followed by an oral dose of 600 mg twice daily for the first 5 postoperative days. The risk
of POAF was reduced from 26% to 11%. Of patients with POAF, 43% were symptomatic in the amiodarone
group vs. 84% in the placebo group. This concords with earlier observations that patients who develop
POAF after amiodarone administration are less tachycardic . Finally, a trial from 2003 randomized 157
[43]