Giuseppe Boriani, Mauro Biffi,
Alessandro Capucci*, Gianluca Botto**, Tiziana Broffoni**, Maurizio Ongari°, Giuseppe
Trisolino°°°, Ida Rubino°°, Mario Sanguinetti°°, Angelo Branzi, Bruno Magnani.
Institute of Cardiology, University of Bologna; *Civil Hospitals Piacenza,
**Como, °Porretta, °°Lugo, °°°Dept. of Emergency, S. Orsola Hospital, Bologna, Italy
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Apart atrial and ventricular ectopic beats, atrial
fibrillation is the most frequently occurring cardiac rhythm disturbance. Its prevalence
in the population increases with age, being 2 to 3 per 1000 between 25 and 35 years, 30 to
40 per 1000 between 55 and 64 years, and 50 to 90 per 1000 between 62 and 90 years1. In the Framingham study, in a 22 to 30-years follow-up, the
incidence of atrial fibrillation was observed to increase progressively with age, with a
modest male predominance, and overall the chance of developing this arrhythmia over two
decades was 2%2.
The social costs caused by atrial fibrillation are relevant: in the United States
atrial fibrillation causes far more hospital admissions than any other arrhythmia,
accounting for almost a million days spent in hospital per year3.
In view of these social costs and of the clinical relevance of atrial fibrillation,
there is the need for rapidly effective drug regimens. In literature different drug
protocols have been proposed for converting atrial fibrillation of recent-onset, however
few studies compared efficacy and safety of different agents in relatively large groups of
patients. In table I4 a summary of data currently
available in literature is shown; however most of these data come from non-controlled
studies where the placebo effect was not evaluated.
Table I - Effects of different agents in conversion of recent onset atrial
fibrillation
Drug
|
Time of
conversion
|
Efficacy (%)
|
Adverse
effects (%)
|
Quinidine p.o
|
< 24 hours
|
59-92
|
3-46
|
Procainamide i.v.
|
< 1.5 hours
|
43-88
|
2-12
|
Dysopyramide i.v.
|
< 8 hours
|
55-86
|
7
|
Propafenone i.v.
|
< 4 hours
|
43-89
|
0-17
|
Propafenone p.o.
|
< 5 hours
|
72-86
|
10-14
|
Flecainide i.v.
|
< 2 hours
|
65-96
|
7-31
|
Flecainide p.o.
|
< 5 hours
|
78-95
|
21-23
|
Amiodarone i.v.
|
< 12 hours
|
25-89
|
7-27
|
Dofetilide i.v.
|
< 2 hours
|
43
|
15
|
Ibutilide i.v.
|
< 1.5 hours
|
31-40
|
25
|
Sotalol i.v.
|
< 4 hours
|
31-85
|
10-20
|
Esmolol i.v.
|
< 40 min
|
6-50
|
14-19
|
Modified from Halperin and Hart 1.
An important requirement in antiarrhythmic treatment is safety; indeed, several
proarrhythmic effects of antiarrhythmic agents may potentially occurr during acute or
chronic treatment of atrial fibrillation5.
For quinidine and other class 1A agents the most harmful side effect is torsade de
pointes. This arrhythmia has been reported during treatment with quinidine in 1-8 % of
treated patients. The risk is higher if the QT interval is prolonged more than 0.55 sec,
in the presence of hypokalemia or bradycardia, however is not strictly related to
quinidine dosage and may occurr even at low or subtherapeutic plasma levels5. Moreover, in patients treated with quinidine for atrial
fibrillation torsade de pointes usually occurs after sinus rhythm resumption, because of
the favouring effect of lower ventricular rate. Fatal complications due to proarrhythmic
effects of quinidine have been recently reported by Tebbe et al6
in a large group of patients treated in-hospital.
For propafenone and flecainide the most harmful proarrhythmic effect is transformation
of atrial fibrillation into flutter with fast ventricular response. Because of the
electrophysiological effects of these agents, slowing of flutter waves may lead to 1:1
atrioventricular conduction, thus with paradoxical increase of ventricular rate and
potential hemodynamic impairment. The electrocardiographic pattern is characterized by QRS
enlargement, for ventricular conduction slowing, so the term "wide QRS complex
tachycardias" has been employed for describing these proarrhythmic effects, whose
occurrence is 3.5-5 % with propafenone or flecainide7.
The adrenergic influence strongly favours these effects, so it is very important to keep
the patient at rest for 3-4 hours after oral loading for atrial fibrillation
cardioversion. An higher risk of proarrhythmic effects, either atrial or ventricular, has
been observed in some subgroups of patients: patients with previous myocardial infarction,
patients with congestive heart failure, patients aged > 80 years, patients with
underlying sick sinus syndrome or other conduction
disturbances, patients with hypokalemia or hypomagnesemia, patients with concomitant renal
or hepatic insufficiency.
Most recently two new drugs, dofetilide and ibutilide, have been studied8,9. Both these agents, administered intravenously, may
cause torsade de pointes with a reported incidence of 8.3% both for dofetilide8 and for ibutilide9.
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