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Waterford et al. Vessel Plus 2022;6:28 https://dx.doi.org/10.20517/2574-1209.2021.115 Page 3 of 12

[21]
further limit administration of ACE inhibitors or ARBs prior to cardiac surgery . Following transcatheter
aortic valve replacement (TAVR), renin-angiotensin system (RAS) inhibitors, including ACE inhibitors,
ARBs, spironolactone, and eplerenone, have been shown to reduce the incidence of post-TAVR atrial
[22]
fibrillation . This data has emerged from a review of 2866 patients in the RASTAVI registry, a 10
institution multicenter registry of patients undergoing TAVR. These medications also reduced
cerebrovascular events, readmissions, and cardiac mortality at 3 years. In the medical literature, a meta-
analysis of 11 randomized controlled trials has shown that ACE inhibitors and ARBs reduced the incidence
of atrial fibrillation by 28% in diverse populations: those with heart failure or hypertension, those who have
undergone cardioversion for atrial fibrillation, and following myocardial infarction . These benefits were
[18]
found only in patients with left ventricular systolic dysfunction and left ventricular hypertrophy. These
results suggest that ACE inhibitors could be used to improve the efficacy of cardioversion.

AMIODARONE
Amiodarone for post-operative atrial fibrillation
Amiodarone is one of the most widely used antiarrhythmic agents and is also commonly used for
prophylaxis of POAF. Interestingly, amiodarone is approved by the Food and Drug Administration for the
treatment of lethal ventricular arrhythmias, an approval which it gained in 1995, but not for the
management of atrial fibrillation. However, it is safe and effective if used with a firm understanding of its
[23]
unique pharmacokinetics as well as the potential for drug interactions and adverse events . Amiodarone is
an iodinated benzofuran derivative and a highly lipophilic drug with unpredictable pharmacokinetics.
Although originally classified as a class III agent due to its ability to prolong refractoriness in cardiac regions
and prevent/terminate re-entry, amiodarone shows antiarrhythmic properties in all four antiarrhythmic
drug classes . Specifically, amiodarone decreases conduction velocity by blocking sodium channels (Class I
[24]
effect), antagonizes non-competitively α and β adrenergic receptors (class II effect), and also exerts a class IV
antiarrhythmic effect by acting as a calcium channel blocker . The consequences of these channel-blocking
[25]
effects can be demonstrated electro-physiologically. Most importantly, potassium-channel blockade slows
repolarization, causing an increase in the duration of the action potential and the refractoriness of cardiac
tissue; this has the effect of prolonging the QT interval. In addition, amiodarone is also uniquely effective in
preventing experimentally-induced atrial electrical remodeling . Finally, dosing and route of
[26]
administration have significant effects on the bioavailability and properties of amiodarone. During loading,
the acute effects of intravenous amiodarone are predominately sodium channel, β-receptor, and calcium
channel blockade. The class III effect is seen after completion of the loading dose because of the increased
[27]
levels of the active metabolite, desethylamiodarone .
Prior to dosing amiodarone, it is important to note the pharmacokinetics. Amiodarone has an oral
bioavailability of 30%-50%, and the rate and extent of amiodarone absorption are increased when taken with
food compared to the fasting state . Amiodarone is metabolized in the liver. During loading, amiodarone
[28]
passes through three phases of distribution: (1) central or vascular distribution occurs over approximately
24 h; (2) peripheral or solid organ distribution occurs over the next 7 days; and (3) deep or fat tissue
distribution occurs over the subsequent 4 weeks. The full antiarrhythmic effect of amiodarone plateaus after
[29]
10 weeks of therapy , and the half-life of amiodarone is 55 days, resulting in significant residual effect after
discontinuation . For hemodynamically stable patients, the loading dose is initiated with intravenous
[30]
amiodarone for better bioavailability: 150 mg intravenous bolus, followed by 1 mg/min for 6 h, followed by
[31]
0.5 mg/min for 18 h or until switched to oral therapy . No dose adjustment is required for renal
impairment. No specific guidelines exist for hepatic impairment; however, given the intermediate first-pass
extraction through the liver, treatment may be initiated at a low-normal dose, with low maintenance
dosing . Similar loading strategies can be used for both atrial and ventricular arrhythmias. When
[32]
[27]
amiodarone is used for rhythm control in atrial fibrillation, typical dosing is 200 mg daily , given after a