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Page 2 of 12 Waterford et al. Vessel Plus 2022;6:28 https://dx.doi.org/10.20517/2574-1209.2021.115

POAF compared to preoperative persistent atrial fibrillation (PEAF) has recently been studied with
[5]
noninvasive 3-dimensional beat-by-beat mapping using a 252-electrode vest . This study has demonstrated
that POAF and PEAF both involve rotor activity, but focal activity is much less common in POAF than
[6]
PEAF. There are several well-established risk factors for POAF , which can broadly be divided into fixed
risk factors and acute ones. Fixed risk factors include increasing age, with patients 60 years and older at
[7-9]
higher risk . Additionally, comorbidities including COPD, diabetes mellitus, and peripheral arterial
disease increase the risk [8,10] . There are also acute risk factors that are related to the postoperative state. For
example, blood transfusion has a dose-dependent relationship with POAF in patients undergoing cardiac
surgery [11-13] .

Prophylactic medications for post-operative atrial fibrillation
Several medications have been studied for prophylaxis of POAF. These include beta-blockers, angiotensin
converting enzyme (ACE) inhibitors, statins, and anti-arrhythmic medications. Beta-blockers are well
known to reduce POAF after cardiac surgery. The mechanism of POAF involves sympathetic activation,
and therefore beta-blockers have been widely studied in its prevention. In a meta-analysis of thousands of
patients included in randomized trials, beta-blockers were found to have an odds ratio of 0.33 for the
prevention of POAF . In fact, the 2006 American College of Cardiology/American Heart
[14]
Association/European Society of Cardiology guidelines for the management of patients with atrial
fibrillation have a class IA recommendation for the use of oral beta-blockers to prevent POAF .
[15]

There have been at least 8 randomized controlled trials of statins in cardiac surgery. In 2006 the ARMYDA-
3 randomized trial of atorvastatin for reduction of POAF was published . This trial enrolled 200 patients
[16]
undergoing elective cardiac surgery with cardiopulmonary bypass and randomized them to 40 mg daily of
atorvastatin or placebo starting 7 days before surgery. Atorvastatin was shown to have a 61% reduction in
the incidence of POAF compared to placebo, and hospital stay was shortened by 0.6 days. In a meta-analysis
from 2010, statins were found to be associated with a 43% risk reduction of POAF as well as shortened
hospital stay, and starting statins earlier before surgery was found to be associated with a greater reduction
[17]
in POAF . In particular, there was a range of starting a statin 2 days to 28 days preoperatively, and meta-
regression analysis of these trials had demonstrated that earlier initiation of a statin before surgery was
[17]
linearly associated with a reduced incidence of POAF . Interestingly, statin dose was not found to correlate
with the magnitude of reduction in POAF.

ACE inhibitors have been suggested as a potential drug to reduce the incidence of atrial fibrillation, both in
medical patients and after cardiac surgery. The mechanism by which ACE inhibitors reduce atrial
fibrillation is thought to involve changes in cardiac structure and function, rather than direct anti-
arrhythmic properties. In animal studies, ACE inhibitors and angiotensin receptor blockers (ARBs) have
been found to prevent left atrial dilatation and atrial fibrosis . Data on ACE inhibitors and ARBs from the
[18]
randomized controlled atrial fibrillation suppression trials II and III (AFIST II and III) have been
published . AFIST II was a randomized trial evaluating the effect of amiodarone and atrial septal pacing on
[19]
the incidence of POAF after coronary artery bypass grafting (CABG) and/or valvular surgery. AFIST III was
a randomized trial evaluating the impact of aortic fat pad maintenance or removal on POAF in patients
undergoing first-time CABG. In these two trials, 48.2% of 338 patients received an ACE inhibitor or ARB
preoperatively. Analysis of these 338 patients has shown that preoperative use of an ACE inhibitor or ARB
had an odds ratio of 0.71 for the development of POAF, but with a non-significant confidence interval . A
[19]
separate trial of irbesartan in 100 consecutive patients undergoing CABG randomized 50 patients to receive
irbesartan for 5 days prior to surgery, and 50 to receive no irbesartan . The incidence of POAF in the
[20]
irbesartan group was 6% vs. 22% in the no irbesartan group, which was statistically significant. Therefore,
this remains an unsolved issue. This lack of evidence combined with hesitation due to the risk of vasoplegia