Pharmacological Cardioversion of Atrial Fibrillation: Which Drugs Are Preferred, Class IC or Class III?

Drugs Are Preferred, Class IC or Class III?

N. B

, V. A. R

, L. D

G

, V. M

, L. L

, G. P

Introduction

It is accepted that pharmacological treatment of recent-onset atrial fibrilla- tion (AF) in order to reset sinus rhythm restoration, if effective and safe, is doubtless the favourite approach, since it is preferred by patients over elec- trical cardioversion. Nonetheless, it must be remembered that the placebo effect is very consistent (> 50% at 12–24 h) for AF duration of 48 h or less.

Also, class I and class III antiarrhythmic drugs are not equivalent, and should be used according to their electrophysiological and pharmacokinetic properties and to their effect on cardiac inotropism, which must be strictly connected to the clinical condition of the patient. Pharmacological treatment can be carried out either intravenously or per os; and the availability of oral- ly administered drugs has made it possible for some AF patients to treat themselves at home.

There are three main factors that must be taken into consideration in choosing the appropriate drug for AF cardioversion: the duration of the arrhythmia, the clinical context in which it takes place, and the ventricular function. AF duration is also the most important factor influencing the pos- sibility of sinus rhythm restoration.

The present review discusses two types of AF: AF of less than 48-h dura- tion and AF of more than 48-h duration. According to the guidelines of the American College of Chest Physicians, in AF of < 48-h duration, antithrom- botic treatment can be avoided due to a low thromboembolic risk linked with cardioversion (< 1%) [1].

Dipartimento di Cardiologia, Ospedale SS. Annunziata, Taranto, Italy

Paroxysmal Atrial Fibrillation (Duration < 48 h)

In this condition, the clinical context and left ventricular function are the most important factors in choosing an antiarrhythmic drug. For lone AF or AF associated with mild hypertension, the class IC antiarrhythmic drugs propafenone and flecainide, administered intravenously, have a priority indi- cation. In patients treated in this manner, the percentage of success is between 85% and 93% for flecainide [2–4] and between 57% and 87% for propafenone [4–6]. The use of these drugs depends not only on their effec- tiveness, but also on the time until sinus rhythm restoration occurs (general- ly within 1 h and often during the drug infusion). In our opinion, the above- mentioned drugs are preferred due to their quick action, which in most cases allows the patient to return home after only a short hospital stay. Also, in AF complicating Wolff-Parkinson-White (WPW) syndrome, propafenone and flecainide can be considered as the drugs of choice. Many studies have show that in such patients the two drugs prolong the anterograde and retrograde refractory periods of the accessory pathway – in patients with either a long or a short refractory period – as well as the complete block of conduction via the accessory pathway [7–16].

These drugs considerably slow down the ventricular response during AF with pre-excited ventricular response [7, 9, 12, 15, 16]. Thus, their effects are two-fold: restoration of sinus rhythm and prolongation of pre-excited beat intervals or block of conduction via the accessory pathway, with slowing down of the ventricular rate. It must be emphasised, however, that drugs such as amiodarone, a class III antiarrhythmic drug, are contraindicated because of their depressive actions on nodal conduction, which may speed up the ventricular response during AF and increase the risk of degeneration to ventricular fibrillation [17]. Instead, in recent years, a single oral loading dose of propafenone and flecainide has been proposed [18–20].

The efficacy of such a regimen is indisputable: a percent conversion of

52–82% and 45–63% has been obtained within 3 h after ingestion of fle-

cainide and propafenone, respectively. The aim of this regimen is to allow

the patient to continue treatment at home, if it proves to be efficacious and

safe. After a pilot study [21], a clinical trial was recently published [22] in

which the safety of home treatment was verified. The study also confirmed

the efficacy of treatment (success rate 94%), a low incidence of side effects,

and a significantly lower number of monthly visits to the emergency room

or hospitalisation. Therefore, in a selected, risk-stratified population of

patients with recurrent AF, a ‘pill-in-the-pocket’ approach is feasible and

safe, is associated with a low rate of adverse events, mostly non-cardiac, and

results in a marked reduction on emergency room visits and hospital admis-

sions. In patients with bundle-branch block or multifascicular block, there is

a potential risk of complete paroxysmal atrioventricular block due to drugs that considerably depress conduction through the His-Purkinje system. The H–V interval is actually prolonged by class IC drugs such as flecainide and propafenone [23, 24]. However, amiodarone does not substantially modify the H–V interval, and in some studies it has been proved to be safe for patients with bundle-branch block [25, 26] and efficacious (50–60%, with a mean time to efficacy of 12 h) [27]. Ibutilide, another class III antiarrhyth- mic drug, may also be used (mean efficacy rate of 30–40% within 90 min) [28, 29] because it does not modify the H–V interval. In the presence of left ventricular dysfunction, the drugs of choice are amiodarone, ibutilide, and dofetilide, since they have been shown to be effective in this clinical setting [29–32]. The most significant potential adverse effect of ibutilide and, with minor misuse, of dofetilide is polymorphic ventricular tachycardia in associ- ation with excess Q–T interval. Class I antiarrhythmic drugs are contraindi- cated due to their specific negative inotropic effect. Amiodarone is the drug of choice in patients with coronary heart disease and after coronary artery by-pass grafting.

Persistent Atrial Fibrillation (Duration > 48 h)

In these patients, the efficacy of antiarrhythmic drugs is progressively lower (not more 50%) with increasing duration of AF. The procedure of choice is external cardioversion with a biphasic waveform (rate of efficacy > 90%) preceded by transoesophageal echocardiography [33] to be sure there are no auricular thrombi. If pharmacological treatment is preferred, the drugs of choice are ibutilide (expected efficacy rate 30–40%, usually within 60 min in a patient population with long-lasting AF and underlying heart disease) [29]

and dofetilide; however, these drug are not on the market in Italy. Also the

expected efficacy of dofetilide in the treatment of, mainly, long-lasting AF is

about 30% [31, 34, 35]. In this clinical context, intravenous amiodarone is

probably less effective. However, if a cardioversion attempt has to be made,

especially in patients with left ventricular dysfunction, amiodarone is likely

to be the most suitable drug. A review of the literature [36–38] by the author

revealed the following: of the patients tested, many of whom presented with

underlying NYHA III–IV [38] heart disease of 3–75 months (on average)

duration, sinus rhythm restoration occurred in 20% administered drug alone

and in 51% administered drug and treated with direct current cardioversion,

whereas other antiarrhythmic drugs had frequently failed. In spite of the

uncertainty surrounding the real efficacy of amiodarone – since the studies

were not controlled – it is clear that amiodarone at least does not reduce per-

formance, in contrast to the majority of class I drugs. Also, dofetilide admin-

istered per os restores sinus rhythm in about one third of patients with AF >

48 h in a relatively short time (91% within 3 days) in a patient population in which myocardial infarction, congestive heart failure, ischaemic heart dis- ease, valvular heart disease, and dilated and obstructive cardiomyopathy were present in > 50% of patients [39].

In conclusion knowledge of both the physiopathology of the different clinical conditions in which AF can occur, and the haemodynamic and elec- trophysiologic effects of the various antiarrhythmic drugs must be used in order to choose the most appropriate drug for restoring sinus rhythm.

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