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Waterford et al. Vessel Plus 2022;6:28 https://dx.doi.org/10.20517/2574-1209.2021.115 Page 7 of 12

Table 2. Randomized trials of intravenous amiodarone as prophylaxis for POAF after cardiac surgery
Number of
Trial (year) Regimen Finding
patients
[46] 1
Guarnieri et al. 300 IV amiodarone 1 g/day for 2 days vs. placebo, starting immediately 35% rate of POAF with
(1999) after surgery amiodarone vs. 47% with
placebo
Beaulieu et al. [47] 250 IV amiodarone 300 mg in the operating room, followed by 15 mg/kg 59.3% rate of POAF with
(2010) per day infusion for 2 days, or placebo amiodarone vs. 40% with
placebo
Tokmakoglu et al. [48] 241 Group 1: metoprolol preoperatively, digoxin intraoperatively, and 16.8% rate of POAF in Group 1,
(2002) metoprolol and digoxin postoperatively 8.3% in Group 2, and 33.6% in
Group 2: amiodarone started in the operating room and continued Group 3
postoperatively (3.45 g total)
Group 3: no antiarrhythmic prophylaxis
[49]
Zebis et al. (2007) 250 IV amiodarone 300 mg on the first postoperative day, then 600 mg of 11% rate of POAF with
oral amiodarone twice daily for 5 days, or placebo amiodarone vs. 26% with
placebo
Yagdi et al. [50] (2003) 157 IV amiodarone 10 mg/kg per day for 2 days, then oral amiodarone 10.4% rate of POAF with
600 mg per day for 5 days, 400 mg per day for 5 days, then 200 mg amiodarone vs. 25% with
per day for 20 days, or placebo placebo

1
IV is intravenous. POAF: Postoperative atrial fibrillation.

patients undergoing elective coronary bypass to placebo or intravenous amiodarone 10 mg/kg per day for 2
days, started within 2 h of intensive care unit arrival . This was followed with oral amiodarone 600 mg
[50]
daily for 5 days, 400 mg daily for 5 days, and 200 mg daily for 20 days. The rate of POAF was 10.4% with
amiodarone and 25% with placebo. Once again, the maximum ventricular rate during atrial fibrillation was
105.9 with amiodarone and 126 with placebo. Hospital stay was 1.0 day shorter with amiodarone. A higher
rate of postoperative hypotension was observed with amiodarone (10.4% vs. 5%), but this was not
significant. Amiodarone was discontinued in 5.2% of patients owing to bradycardia less than 60 beats per
minute or a corrected QT interval > 440 ms, although this is quite a low threshold in corrected QT interval
for discontinuation. None of these patients had POAF, and bradycardia resolved after discontinuation.

Next, we review briefly a study of rate versus rhythm control for POAF . In this study, 523 patients were
[51]
randomized to either rate control or rhythm control for POAF, with findings showing a similar length of
hospitalization and a rate of cerebrovascular thromboembolic events less than 1% per patient-month in both
groups, although more patients in the rhythm control arm were in sinus rhythm at 60 days. However, 26.7%
of patients in the rate control group received amiodarone or underwent cardioversion, and 23.8% of patients
in the rhythm control group did not complete a full course of amiodarone mostly due to side effects. The
rate of amiodarone discontinuation due to side effects seems high compared with anecdotal clinical practice.
Overall, the rate of nonadherence makes the two treatment groups difficult to compare, the baseline rate of
thromboembolic events was very low, and the trial demonstrates the challenges of performing randomized
trials in this space. Nonetheless, both groups received amiodarone, and this shows the ubiquity of its use.

Finally, it is important to note that rates of POAF are similar with on-pump CABG and off-pump CABG. In
a retrospective review of 1836 patients undergoing CABG, POAF occurred in 18.3% of on-pump CABG
patients and 19.3% of off-pump CABG patients . In both groups, the peak incidence was between the
[52]
second and third postoperative days. Similarly, in an analysis of the Randomized On Versus Off Bypass trial
of on-pump vs. off-pump CABG, POAF occurred in 25.4% of on-pump CABG patients and 27% of off-
pump CABG patients . As a result, prophylaxis is warranted for all CABG patients.
[53]