Download Pharmacological Cardioversion of Atrial Fibrillation: Which Drugs

Pharmacological Cardioversion of Atrial Fibrillation: Which
Drugs Are Preferred, Class IC or Class III?
N. BALDI, V. A. RUSSO, L. DI GREGORIO, V. MORRONE, L. LICONSO, G. POLIMENI
Introduction
It is accepted that pharmacological treatment of recent-onset atrial fibrillation (AF) in order to reset sinus rhythm restoration, if effective and safe, is
doubtless the favourite approach, since it is preferred by patients over electrical 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 orally 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 possibility of sinus rhythm restoration.
The present review discusses two types of AF: AF of less than 48-h duration 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, antithrombotic treatment can be avoided due to a low thromboembolic risk linked
with cardioversion (< 1%) [1].
Dipartimento di Cardiologia, Ospedale SS. Annunziata, Taranto, Italy
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N. Baldi et al.
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 indication. 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 effectiveness, but also on the time until sinus rhythm restoration occurs (generally within 1 h and often during the drug infusion). In our opinion, the abovementioned 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 flecainide 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 admissions. In patients with bundle-branch block or multifascicular block, there is
Pharmacological Cardioversion of Atrial Fibrillation
97
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 antiarrhythmic 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 association with excess Q–T interval. Class I antiarrhythmic drugs are contraindicated 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 performance, in contrast to the majority of class I drugs. Also, dofetilide admin-
N. Baldi et al.
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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 disease, 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 electrophysiologic effects of the various antiarrhythmic drugs must be used in
order to choose the most appropriate drug for restoring sinus rhythm.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Singer DE, Albers GW, Dalen JE et al (2004) Antithrombotic therapy in atrial fibrillation. The Seventh ACCP Conference on antithrombotic and thrombolytic therapy. Chest 126:429S–456S
Borgeat A, Goy JJ, Maendly R et al (1986) Flecainide versus quinidine for conversion of atrial fibrillation to sinus rhythm. Am J Cardiol 58:496–498
Suttorp MJ, Kingma JH, Lie-A-Hauel et al (1989) Intravenous flecainide versus
verapamil for acute conversion of paroxysmal atrial fibrillation or flutter to sinus
rhythm. Am J Cardiol 63:693–696
Suttorp MJ, Kingma JH, Jessuron EK et al (1990) The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus
rhythm. J Am Coll Cardiol 16:1722–1727
Bianconi L, Boccadamo R, Pappalardo A et al (1989) Effectiveness of intravenous
propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J
Cardiol 64:335–338
Bertini G, Conti A, Fradella G et al (1990) Propafenone versus amiodarone in field
treatment of primary atrial tachydysrhythmias. J Emerg Med 8:15–20
Neuss M, Buss J, Schlepper M et al (1983) Effects of flecainide on electrophysiological properties of accessory pathways in the Wolff-Parkinson-White syndrome. Eur
Heart J 4:347–353
Hellenstrand KJ, Nathan AW, Bexton RS et al (1984) Electrophysiologic effects of
flecainide acetate on sinus node function anomalous, atrioventricular connections
and pacemaker threshold. Am J Cardiol 53(Suppl B):30–38
Breithardt G, Borggrefe M, Wiebringhaus E et al (1984) Effect of propafenone in
the Wolff-Parkinson-White syndrome: electrophysiological findings and long-term
follw-up. Am J Cardiol 54:29D–39D
Kim SS, Lae R, Ruffy R (1986) Treatment of paroxysmal supraventricular tachycardia with flecainide acetate. Am J Cardiol 58:80–85
Shen EN, Keung E, Huicke E et al (1986) Intravenous propafenone for termination
of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, cross-over study. Ann Intern Med 105:655–659
Hammil SC, Mc Laran CJ, Wood DL et al (1987) Double blind study of intravenous
propafenone for paroxysmal supraventricular re-entrant tachycardia. J Am Coll
Cardiol 9:1364–1368
Ludmer PL, Mc Cowan NE, Antman EM et al (1987) Efficacy of propafenone in
Wolff-Parkinson-White syndrome: electrophysiologic findings and long-term fol-
Pharmacological Cardioversion of Atrial Fibrillation
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
99
low-up. J Am Coll Cardiol 9:1357–1363
Dubuc M, Kus T, Campa MA et al (1989) Electrophysiologic effects of intravenous
propafenone in Wolff-Parkinson-White syndrome. Am Heart J 117:370–376
Kappenberger LJ, Fromer MA, Shenasa M et al (1985) Evaluation of flecainide acetate in rapid atrial fibrillation complicating Wolff-Parkinson-White syndrome. Clin
Cardiol 8:321–326
Manolis AS, Salen DN, Estes NAM et al (1989) Electrophysiologic effects, efficacy
and tolerance of class IC antiarrhythmic agent in Wolff-Parkinson-White syndrome. Am J Cardiol 63:746–750
Vitale P, Stefano R, Auricchio A (1986) Possibile pericolosità dell’amiodarone per
via endovenosa rapida nel corso di tachicardia da rientro in soggetti con WolffParkinson-White. G It Cardiol 16:969–974
Capucci A, Lenzi T, Boriani G et al (1992) Effectiveness of loading oral flecainide
for converting recent-onset atrial fibrillation to sinus rhythm in patients without
organic heart disease or with only systemic hypertension. Am J Cardiol 70:69–72
Capucci A, Boriani G, Rubino I et al (1994) A controlled study on oral propafenone
versus digoxin plus quinidine in converting recent-onset atrial fibrillation to sinus
rhythm. Int J Cardiol 43:305–313
Capucci A, Boriani G, Botto GL et al (1994) Conversion of recent-onset atrial fibrillation by a single oral loading dose of propafenone or flecainide. Am J Cardiol
74:503–505
Baldi N, Russo VA, Morrone V et al (1998) Home treatment of recent-onset atrial
Fibrillation with a single oral dose of flecainide or propafenone: an efficacious,
reproducible and safe procedure. G It Cardiol 29 (Suppl 5):380–383
Alboni P, Botto GL, Baldi N et al (2004) Out patients treatment of recent-onset
atrial fibrillation with the ‘pill in the pocket’ approach. N Engl J Med 351:2384–2391
Hellenstrand KJ, Bexton RS, Nathan AW et al (1982) Acute electrophysiological
effects of flecainide acetate on cardiac conduction and refractoriness in man. Br
Heart J 48:140–148
Pristowsky EN, Heger JJ, Chilson DA et al (1984) Antiarrhythmic and electrophysiologic effect of oral propafenone. Am J Cardiol 54:26D–28D
Benaim R, Uzan C (1978) Les effects antiarythmiques de l’amiodarone injectable (à
propos de 153 cas). Rev Med 19:1959–1963
Morady F, Scheinman MM, Shen E et al (1983) Intravenous amiodarone in the
acute treatment of recurrent symptomatic ventricular tachycardia. Am J Cardiol
51:156–159
Galve E, Rius T, Ballester R et al (1996) Intravenous amiodarone in treatment of
recent-onset atrial fibrillation:results of a randomized, controlled study. J Am Coll
Cardiol 27:1079–1082
Vos MA, Golitsyn RS, Stangl K et al (1998) Superiority of ibutilide (a new class III
agent) over DL-sotalol in converting atrial flutter and atrial fibrillation. The
Ibutilide-Sotalol Comparator Study Group. Heart 79:568–575
Stambler BS, Wood MA, Ellenbogen KA et al (1996) Efficacy and safety of repeated
doses of ibutilide for rapid conversion of atrial fibrillation and flutter. Ibutilide
Repeat Dose Study Investigators. Circulation 94:1613–1621
Deedwania PC, Singh BN, Ellenbogen K et al (1998) Spontaneos conversion and
maintenance of sinus rhythm by amiodarone in patients with heart failure and
atrial fibrillation: observations from the veterans affairs congestive heart failure
survival trial of antiarrhythmic therapy (CHF-STAT). Circulation 98:2574–2579
Falk RH, Pollak A, Singh SN et al (1997) Intravenous dofetilide, a class III
100
32.
33.
34.
35.
36.
37.
38.
39.
N. Baldi et al.
antiarrhythmic agent, for termination of sustained atrial fibrillation or flutter. J
Am Coll Cardiol 29:385–390
Top-Pedersen, Moller M, Bloch-Thomsen PE et al (1999) Dofetilide in patients with
congestive heart failure and left ventricular dysfunction. Danish Investigations of
Arrhythmias and Mortality on Dofetilide Study Group. N Engl J Med 341:857–865
Klein AL, Grimm RA, Murray RD et al (2001) Use of trans-oesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med
344:1411–1420
Norgaard BL, Wachtell K, Christensen PD et al (1999) Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish
Dofetilide in Atrial Fibrillation and Flutter Study Group. Am Heart J 137:1062–1069
Lindeboon JE, Kingma JH, Crjins HJ et al (2000) Efficacy and safety of intravenous
dofetilide for rapid termination of atrial fibrillation and atial flutter. Am J Cardiol
85:1031–1033
Horowitz LN, Spielman SR, Greenspan AM et al (1985) Use of amiodarone in the
treatment of persitent and paroxysmal atrial fibrillation resistant to quinidine therapy. J Am Coll Cardiol 6:1402–1407
Blevius RD, Kerin NZ, Benaderet D et al (1987) Amiodarone in the management of
refractory atrial fibrillation. Arch Intern Med 147:1401–1404
Gosselink ATM, Crijns HJ, Van Gelder IC et al (1992) Low-dose amiodarone for
maintenance of sinus rhythm after cadioversion of atrial fibrillation or flutter.
JAMA 267:3289–3293
Singh S, Zoble RG, Yellen L et al (2000) Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation
or atrial flutter: the Symptomatic Atrial Fibrillation Investigative Research on
Dofetilide (SAFIRE-D) Study. Circulation 102:2385–2390