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European Review for Medical and Pharmacological Sciences
2012; 16: 242-253
Atrial fibrillation and the pharmacological
treatment: the role of propafenone
A. SESTITO, E. MOLINA*
Department of Cardiology, School of Medicine, Catholic University of the Sacred Heart, Rome (Italy)
*Department of Pharmacology, School of Medicine, University of Parma (Italy)
Abstract. – Background: Atrial fibrillation
is the most frequent cardiac rhythm disturbance,
with prevalence increasing with age. This disease
is a major risk factor for ischaemic stroke. The
costs resulting from atrial fibrillation are really
impressive. Pharmacological agents are the first
line therapy for the management of atrial fibrillation. Antiarrhythmic drugs are used to terminate
arrhythmias, as acute treatment for conversion of
recent onset atrial fibrillation, and to maintain sinus rhythm, as chronic therapy for prevention of
atrial fibrillation recurrences. Among antiarrhythmic agents, drugs that inhibit early sodium current (as propafenone) are proven effective in atrial fibrillation. In this review, the most relevant data on propafenone are provided.
Discussion: The development of a sustainedrelease formulation of propafenone allowed to
reduce the wide fluctuations in plasma levels observed with the immediate release preparation,
improving compliance and adherence to therapy,
by simplifying the dosing regimen from 3 to 2
daily doses. Propafenone resulted an effective
measure as acute treatment for conversion of recent onset atrial fibrillation, and to maintain sinus rhythm, as chronic therapy for prevention of
atrial fibrillation recurrences. In several clinical
studies, strong increases of arrhythmia-free periods as well as marked increases in time to recurrence of symptomatic atrial fibrillation, such as
paroxysmal supraventricular tachycardia and
paroxysmal atrial fibrillation were observed. In
particular, well-designed clinical studies demonstrated in large patient populations the efficacy of
propafenone at several doses. At the suggested
doses propafenone is usually well tolerated.
Conclusion: The risk of increased occurrence
of regular supraventricular arrhythmia or paroxysmal supraventricular tachycardia has been overestimated for propafenone, because this adverse
event was seen in all treatment groups, including
placebo, with the same (and low) frequency.
Key Words:
Atrial fibrillation (AF), Acute onset AF, Prevention of
AF recurrences, Antiarrhythmic drugs, Propafenone.
242
Introduction
Atrial fibrillation is a major clinical problem
and the most frequently occurring cardiac rhythm
disturbance1-6. Its prevalence increases with age:
2-3‰ between 25 and 35 years, 30-40‰ between 55 and 65 years, 50-90‰ between 62 and
90 years1-3,5. The prevalence of atrial fibrillation
is expected to increase for several factors, first of
all for the progressive increase in longevity of
worldwide populations1,2,6. According to a 2005
estimate6, in USA there were 3.03 millions of
atrial fibrillation patients and this figure could
reach 7.56 millions in 2050.
Atrial fibrillation is a strong risk factor for ischaemic stroke (approximately 3- to 5-fold excess risk), with associated clinical problems and
increased mortality rates (1.5- to 1.9-fold mortality risk)2-4,6.
Together with its complications, atrial fibrillation is a major cause of health care consumption,
costs and poor quality of life6,7. The costs resulting from atrial fibrillation are really impressive2,3,5. In USA it has been estimated that this
disease is responsible for more than 1 million
days of hospitalization per year5.
Even if the pathophysiology of atrial fibrillation
is not yet completely understood, there is evidence
that the cardiac remodeling plays a major role in the
disease process4. A high number of factors responsible for onset of atrial fibrillation, usually indicated
as “triggers”, has been recognized8-10. Among them,
sympathetic or parasympathetic stimulation, bradycardia, atrial premature beats, tachycardia, accessory atrio-ventricular pathways, and acute atrial
stretch are included8. In particular, it has been
demonstrated that a wide part of atrial premature
beats, involved in paroxysms of atrial fibrillation,
originate in the pulmonary veins9. The intrinsic cardiac autonomic nervous system is thought to play a
crucial role in the atrial remodeling process10.
Corresponding Author: Alfonso Sestito, MD; e-mail: [email protected]
Atrial fibrillation and the pharmacological treatment: the role of propafenone
The clinical relevance and the high costs of
atrial fibrillation account for the need of effective
drug treatment5.
As for the management of atrial fibrillation,
the main therapeutic strategies include:
•
•
•
•
Rate control;
Termination of arrhythmia;
Prevention of recurrences;
Prevention of thromboembolic events11.
Pharmacological agents are the first line therapy for rhythm management in atrial fibrillation1,6.
Antiarrhythmic drugs are used to terminate arrhythmias and maintain sinus rhythm6,11.
Efficacy and safety profiles are extremely important issues in the choice of an antiarrhythmic
agent, but also the dosing convenience (allowing
high patient compliance) should be taken in due
account11. According to current guidelines, it is
suggested to select an antiarrhythmic drug considering some main factors, in order to identify
the best therapeutic strategy:
•
•
•
•
•
Symptoms presentation;
Atrial fibrillation characteristics;
Presence of cardiovascular diseases;
Patient age and medical conditions;
Treatment goals6.
Among antiarrhythmic agents, drugs that inhibit early sodium current (as propafenone and
flecainide) are proven effective in atrial fibrillation1,5,12,13. The most widely used antiarrhythmic
drugs6 are listed in Table I.
According to most recent guidelines and updated meta-analyses, as well as to the Author’s
personal caseload, it is possible to anticipate
some general considerations on the pharmacological approach to atrial fibrillation.
As for other chronic treatments, also for antiarrhythmic drugs the choice of the proper therapy should balance at the best efficacy and safety.
The group of antiarrhythmic drugs includes
different molecules showing each a typical pro-
file of efficacy, safety and convenience. Table II
reports some observations on main antiarrhythmic agents6,14-16.
We can state, therefore, that propafenone,
thanks to its clinical efficacy associated to a good
safety (in particular to a reduced risk of proarrhythmic effect), can represent an important measure in the management of atrial fibrillation patients not showing cardiac structural alterations.
In addition, this drug, due to the availability of
vials for intravenous use, immediate release
tablets, and sustained release capsules, allows to
develop various treatment schedules and to adapt
the therapy according to different needs.
Focus on Propafenone
Propafenone is a powerful Ic class antiarrhythmic agent, with demonstrated effectiveness
against a variety of cardiac arrhythmias12-14. This
agent shows a marked inhibitory effect on the
sodium channel and some beta-blocking activity5,14-17.
The original formulation of oral propafenone
immediate release was rapidly absorbed by gastrointestinal tract and metabolized by liver,
needing a 3 times daily administration 13,17 .
Propafenone 150-300 mg tid is associated to a
half-life of 5-7 hours, wide fluctuations in peaktrough plasma concentrations, and a marked interindividual variability17,19. To solve these problems, a sustained-release preparation (SR) has
been subsequently developed, improving compliance, efficacy, and safety12,13,17,18. Thank to its
prolonged half-life (12 hours), this latter
propafenone formulation allows a twice daily administration, with better compliance and adherence to therapy12,13,17,18. In addition, based on the
official data on propafenone pharmacokinetics
derived from SPC, we underline the importance
of the curves reported in Figure 1.
Propafenone undergoes extensive hepatic metabolization: the main products of oxidative metabolism are 5-hydroxy-propafenone and hydroxy-methoxy-propafenone5,17. In particular, 5hydroxy-propafenone shows a pharmacodynamic
Table I. Main antiarrhythmics drugs.
Sodium channel blockers
Class Ia
Class Ic
Disopyramide, procainamide, quinidine
Flecainide, propafenone
Potassium channel blockers
Class III
Amiodarone, dofetilide*, ibutilide, sotalol
*USA only. (Adapted from 6).
243
A. Sestito, E. Molina
Table II. Selected data on main antiarrhythmics.
Some drugs, relatively more recent (as propafenone, flecainide, procainamide and sotalol), are at least as effective as some
less recent agents, as quinidine and disopyramide.
At the same time, propafenone, flecainide, procainamide and sotalol are better tolerated than quinidine and disopyramide.
Among the most active agents, the proarrhythmic effect is less frequent with propafenone and amiodarone.
As for proarrhythmic effect, no statistically significant differences were found when comparing propafenone and amiodarone with placebo.
In particular, in the Ic class propafenone shows a lower frequency of proarrhythmic effects as compared with flecainide.
Propafenone is a powerful Ic antiarrhythmic agent, widely used for sinus rhythm restoration and maintenance.
In meta- and mixed-analyses, sotalol and propafenone were evaluated as for the safety profile in the widest patients populations (more than 1,000 patients), as compared with amiodarone (n = 437) or flecainide (n = 114).
(Adapted from 6, 14, 15, 16).
profile similar to the parent drug, thus contributing to the therapeutic efficacy5,17.
As for pharmacodynamics, the principal activities of propafenone are arrhythmia suppression,
intracardiac conduction and beta-adrenergic
blockade5,17.
Propafenone Clinical Efficacy
Propafenone resulted an effective measure as
acute treatment, for conversion of recent onset
atrial fibrillation 5,11,20-30 and to maintain sinus
rhythm, as chronic therapy, for prevention of atrial fibrillation recurrences11-13,31-35.
Figure 1. Propafenone plasma levels following repeated oral doses of slow-release formulation (325 and 425 mg) and immediate-release (150 and 300 mg).
244
Atrial fibrillation and the pharmacological treatment: the role of propafenone
Acute Treatment: Conversion to
Sinus Rhythm
The objectives of acute treatment of atrial fibrillation are:
• To reduce atrial fibrillation duration;
• To avoid the need for anticoagulants, required
for atrial fibrillation that lasts more than 48 h;
• To reduce hospital stay5.
• At ≤ 1 hour, only intravenous propafenone
was effective;
• At ≤ 3 hours, all treatments were effective, except amiodarone;
• At ≤ 8 hours, all comparisons vs placebo were
statistically significant5.
Figure 2. Efficacy of propafenone (PFN) or placebo (PLA)
in acute-onset atrial fibrillation: cumulative results of 7 clinical studies. (Adapted from 5).
These data5 are shown in Figure 3.
The early onset of therapeutic action induced by
propafenone has been demonstrated also in a shortterm study in comparison with quinidine in patients
with recent-onset atrial fibrillation (≤ 48 h)28.
81 patient have been randomized to the following treatments:
• Propafenone 300 mg bolus per os, followed by
further 300 mg after 8 hours, if the sinus
rhythm was not reached (n = 43);
Sinus rhythm (%)
The acute treatment is usually required in atrial fibrillation of recent onset, such as an arrhythmia of <48 to 72 hours duration5.
Propafenone as intravenous formulation resulted effective in converting atrial fibrillation to
sinus rhythm in several studies5,21,22. The dosing
scheme was an intravenous single bolus (2
mg/kg) or an intravenous bolus (2 mg/kg) followed by an intravenous infusion5.
After an intravenous bolus, the efficacy rates
were of 51% to 88%, increasing up to 91% with
intravenous infusion5.
When considering efficacy, also the time of sinus rhythm restoration must be considered: in a
meta-analysis of clinical trials, the proportions of
patients attaining sinus rhythm with intravenous
propafenone were: at 1 hour 57%; at 2 hours
66%; at 4 hours 51%; at 8 hours 69%5.
The use of propafenone as oral loading doses
(450 mg to 600 mg) appears a useful alternative
to the intravenous route, producing therapeutic
plasma levels of propafenone and its active
metabolite, 5-hydroxy-propafenone5,11,20, 22-29.
At doses of 450 mg to 600 mg, propafenone
resulted associated with a success rate between
66% and 76% at 8-12 hours from administration5.
The efficacy of oral loading with propafenone
in converting atrial fibrillation to sinus rhythm
has been demonstrated versus placebo and active
treatments in several studies5,11,20, 22-29.
Figure 2 shows the cumulative results of 7 comparative studies versus placebo in 934 patients5.
A comparison of different drug protocols, including intravenous and oral loading
propafenone, intravenous amiodarone, oral flecainide, and placebo, with assessments made at
different times, showed that:
Figure 3. Efficacy of intravenous amiodarone, intravenous
propafenone, oral propafenone, flecainide, and placebo:
conversion rate for sinus rhythm (SR) at ≤ 8 hours. (Adapted from 5).
245
A. Sestito, E. Molina
• 1 mg digoxin iv, followed by oral quinidine
loading dose: 400 mg per os and additional
200 mg every 2 hours (n = 38)28.
The length of treatment was not exceeding 24
hours28.
At 8 hours propafenone was associated with a
success rate of 83.3% versus 53% of quinidine (p
= 0.01)28.
Also the time to restore sinus rhythm was significantly shorter with propafenone than quinidine: 165 minutes versus 360 minutes (p =
0.05)28.
Figure 4 shows the number of patients with
atrial fibrillation in this study28.
Naccarelli et al11 carried out an overview of
clinical trials on efficacy of antiarrhythmic drugs
in converting and maintaining sinus rhythm. In
this analysis the best pharmacological strategies
for acute control of atrial fibrillation were evaluated.
Comparative efficacy of oral quinidine, sotalol, oral bolus propafenone, and intravenous
amiodarone versus and placebo, estimated as
conversion rates for recent-onset atrial fibrillation, is reported in Figure 5.
According to the data shown in Figure 5, in
atrial fibrillation11 of recent onset the highest efficacy was observed for propafenone 300 mg bid.
In the management of paroxysmal atrial fibrillation, propafenone and flecainide resulted
the most effective agents in order to obtain the
conversion to sinus rhythm29. Some differences
were observed, however, when considering the
control exerted by these two drugs on heart rate
in patients who failed cardioversion29. In fact,
flecainide induced a reduction of heart rate from
9% to 13%, a result comparable to that observed with placebo, while propafenone was associated with a reduction of heart rate from
15% to 31%29. Very likely, this result is related
with the beta-blocking properties typical of
propafenone29.
The marked activity of propafenone, as acute
treatment by oral route, and the quick onset of
therapeutic action led to the “pill in the pocket”
strategy, implying the drug is taken per os shortly
after a symptomatic recurrence appears: this approach was described by Alboni et al30 in 2004.
Obviously, the “pill in the pocket” approach,
which can be performed out of hospital, should
be adopted only in selected patients, who already
experienced the safety of such a treatment during
a hospital stay.
Chronic treatment: Sinus Rhythm
Maintenance and Prevention of
Atrial Fibrillation Recurrences
Several benefits are associated to sinus rhythm
maintenance:
• Prevention of atrial electrical remodelling,
slowing disease progression;
• Improvement of hemodynamics by restoring
atrial transport function;
• Enhancement of exercise capacity;
• Relief of symptoms, with quality of life improvement;
• Reduction of thromboembolic events.
Figure 4. % of patients with atrial fibrillation who received propafenone or quinidine per os. (Adapted from 28).
246
% cardioversion
Atrial fibrillation and the pharmacological treatment: the role of propafenone
Figure 5. Antiarrhythmic conversion of recent-onset atrial fibrillation: comparative efficacy of different pharmacological
agents. (Adapted from 9).
According to International Guidelines, in order to prevent recurrences of atrial fibrillation, it
is often suggested a pharmacological treatment
that can be performed by antiarrhythmic agents,
able to maintain sinus rhythm36. Among antiarrhythmic agents, propafenone resulted an effective measure in several clinical studies, allowing
strong increases of arrhythmia-free periods as
well as marked increases in time to recurrence of
symptomatic atrial fibrillation: thus propafenone
is of value in the prophylaxis of both paroxysmal
supraventricular tachycardia and paroxysmal
atrial fibrillation11-13,31-35.
The efficacy of immediate release propafenone
formulation was already demonstrated as soon as
the drug became available in Europe and USA in
the 80’s12.
ERAFT and his sister trial from North America RAFT have been designed to definitely assess the effectiveness of the SR (Sustained Release) formulation in the prophylaxis of atrial
fibrillation recurrences12,13. Therefore, for the
most recent SR propafenone formulation, these
two large and well-conducted studies are described12,13.
The ERAFT (the European Rythmol/Rytmonorm Atrial Fibrillation Trial) was a multicenter
prospective, randomized double-blind, placebocontrolled parallel group study, that compared
propafenone 325 mg bid, propafenone 425 mg
bid, and placebo in a large patient population12.
The objective of the trial was to demonstrate the
drug efficacy in the prevention of recurrences of
symptomatic paroxysmal atrial fibrillation12. The
primary efficacy analysis was based on the arrhythmia-free period form 5th day from randomization to first recurrence of symptoms of atrial
fibrillation (primary endpoint)12. A total of 293
patients were randomized to the 3 treatment
arms:
• 111 to propafenone 325 mg bid;
• 89 to propafenone 425 mg bid;
• 93 to placebo bid12.
The results of the trial showed, as primary efficacy analysis, that the most frequent diagnosis
of symptomatic arrhythmia observed after 5 days
was atrial fibrillation12.
It has been evidenced a significant increase in
the arrhythmia-free period from 5th day from randomization to first recurrence in the 2
propafenone groups compared with placebo: 325
mg bid p = 0.004 and 425 mg bid p = 0.003
(Table III)12.
The median duration of arrhythmia-free period was 9 days for the placebo group, 35 days
for the propafenone SR 325 mg bid group, and
44 days for the propafenone SR 425 mg bid
group (p < 0.001 in favour of propafenone in
both comparisons versus placebo)12. These differences resulted even greater wen adopting the
per-protocol analysis, such as when the analysis was restricted to patients adherent to study
protocol, instead of performing the full data
analysis (Figure 6)12.
247
A. Sestito, E. Molina
Table III. Results of the ERAFT Study: tachyarrhythmia-free periods (days) from day 5th of randomization in the 2
propafenone groups and placebo.
Propafenone SR dose (twice daily)
Variable
Patients completing with terminating event*
AEC diagnosis
AF
Atrial flutter
Comparison of tachycardia-free periods
Kaplan-Meier median
Range
p value†
Log-rank
Hazard ratio
95% CI for hazard ratio‡
325 mg (n 107) (%)
425 mg (n 83) (%)
Placebo (n 88) (%)
66 (61.7)
41 (49.4)
65 (73.9)
65 (60.7)
1 (0.9)
39 (47.0)
2 (2.4)
65 (73.9)
0 (0.0)
35.0
0-105
44.0
0-101
9.0
0-106
0.004
0.60
0.43-0.86
0.003
0.55
0.36-0.82
–
_
_
*Patients had a terminating event if they had symptomatic AF or atrial flutter according to the AEC. †Value was based on the
test of each propafenone SR dose versus placebo, and statistical significance was based on a closed testing procedure. ‡Hazard
ratio was based on the proportional hazard model with propafenone SR dose versus placebo as single independent variable.
AEC = Arrhythmia Events Committee; CI = confidence intervals. (Adapted from 12).
In conclusion, the ERAFT study demonstrated
in a large patient population the efficacy of
propafenone SR formulation12. The results of this
trial, using propafenone SR 2 times daily, are
consistent with the results of other studies adopting the immediate release formulation 3 times
daily12. In particular, the PSVT (UK Propafenone
Paroxysmal Supraventricular Tachycardia) study,
conducted on patients with two or more recurrences of atrial fibrillation, compared
propafenone 300 mg bid versus placebo, followed by 300 mg tid versus placebo in a
crossover design12,32. The mean time to arrhythmia was 11 days in the placebo group vs > 98
days in the propafenone bid group12,32.
The RAFT (Rythmol Atrial Fibrillation Trial)
was a randomized double-blind, placebo-controlled study, carried out in USA, that compared
propafenone 225 mg bid, propafenone 325 mg
bid, propafenone 425 mg bid, and placebo in patients not previously exposed to this agent13.
The objective of the trial was to demonstrate
the propafenone efficacy in reducing symptomatic arrhythmia recurrences in patients with
atrial fibrillation13.
The primary outcome event was the first of
electrocardiograms coded as atrial fibrillation,
atrial flutter or paroxysmal supraventricular
tachycardia. Patients completed the study if they
had an outcome event or if they finished the 39
weeks of follow-up.
248
A total of 523 patients were randomized to the
4 treatment arms:
•
•
•
•
126 to propafenone 225 mg bid;
135 to propafenone 325 mg bid;
136 to propafenone 425 mg bid;
126 to placebo bid.
The analysis of all patients showed a median
time to the occurrence of a primary outcome
event of 41 days in placebo group, of 112 days in
the propafenone 225 mg group, 291 days in the
propafenone 325 mg group, and >300 days in the
propafenone 425 mg bid group (Table IV).
In the primary efficacy analysis, statistically
significant differences between placebo and
propafenone were recorded:
• p < 0.001 for propafenone 425 mg;
• p < 0.001 for propafenone 325 mg;
• p = 0.014 for propafenone 225 mg13.
These data are shown in Figure 713.
The survey of Naccarelli at al11, already quoted for acute treatment of atrial fibrillation, included also an evaluation of the efficacy of antiarrhythmic drugs in the recurrence prevention.
According to the results of 6 main studies,
comparing oral propafenone, flecainide, sotalol,
and quinidine, it can be evidenced that
propafenone was significantly more effective
Atrial fibrillation and the pharmacological treatment: the role of propafenone
Figure 6. Tachyarrhythmia-free period (absence of symptomatic atrial fibrillation or atrial flutter) from day 5 of randomization. (Adapted from 10).
than sotalol and quinidine (p < 0.01 and p < 0.05,
respectively), while propafenone and flecainide
were equally effective.
Safety
In the most clinical studies propafenone resulted well tolerated, with only minor side-effects11,12,13,17,34-36.
In the RAFT study, for instance, adverse
events were generally comparable among the
placebo twice daily group and the two
propafenone groups, 225 and 325 mg bid 12 .
When comparing the safety profiles of
propafenone and flecainide, it can be observed
that the frequency of side effects not requiring
treatment withdrawal was significantly higher
with flecainide: 48% versus 8% of propafenone
(p < 0.01)29.
Interestingly, in the RAFT study, propafenone
did not result associated with an increased occur249
A. Sestito, E. Molina
Figure 7. RAFT Study: efficacy analysis in all randomized patients. Time to first symptomatic arrhythmia recurrence.
(Adapted from 11).
Table IV. Results of RAFT study: efficacy of propafenone 225, 325, and 425 mg versus placebo.
Propafenone SR dose or placebo (all twice daily)
Parameter
All randomized patients
Patients with symptomatic outcome
arrhythmia documented by
electrocardiogram
Time to outcome arrhythmia
Kaplan-Meier, median (d)
Range (d)
Log-rank p value vs placebo
Hazard ratio (propafenone: placebo)
95% CI for hazard ratio
Patients in sinus rhythm after
loading period
Patients with symptomatic outcome
arrhythmia documented by
electrocardiogram
Time to outcome arrhythmia Kaplan-Meier,
median (d)
Range (d)
Log-rank p value vs placebo
Hazard ratio (propafenone:placebo)
95% CI for hazard ratio
CI = confidence intervals. (Adapted from 11).
250
225 mg
325 mg
425 mg
Placebo
126
66 (52%)
135
56 (42%)
136
41 (30%)
126
87 (69%)
112
291
300
41
0-285
0.014
0.672
(0.488-0.927)
0-293
0.001
0.434
(0.309-0.609)
0-300
0.001
0.353
(0.243-0.513)
0-289
–
–
–
124
60 (48.4%)
132
54 (40.9%)
131
36 (27.5%)
124
84 (67.7%)
149
287
296
39
0-281
0.002
0.604
(0.433-0.842)
0-289
0.001
0.438
(0.310-0.619)
0-296
0.001
0.319
(0.216-0.473)
0-285
–
–
–
Atrial fibrillation and the pharmacological treatment: the role of propafenone
Table V. Risk of proarrhythmic effect with propafenone and flecainide, according to the analysis of the Cochrane Collaborative Group on the use of antiarrhythmic agents in the maintenance therapy after cardioversion in atrial fibrillation.
Drugs
Flecainide
Propafenone
Peto method°
Nr of studies
Nr of patients
3
5
149
1098
Effect size° (95% IC)
5.97 (1.67-21.34)
1.52 (0.33-7.02)
(Adapted from 28).
rence of supraventricular arrhythmia or paroxysmal supraventricular tachycardia, as well as of
asymptomatic atrial fibrillation13. The increase in
the occurrence of regular supraventricular arrhythmia with ECG, typical for atrial flutter or
paroxysmal supraventricular tachycardia, was a
supposed effect widely reported when the class
Ic antiarrhythmic drugs was introduced on the
market13.
The Authors of RAFT report suggest that this
problem has been possibly overestimated for
propafenone, as it was seen in all treatment
groups, including placebo, with the same and
low frequency13.
These data were recently confirmed by the
Cochrane Collaborative Group, who carried out a
systematic review on the efficacy and safety of
antiarrhythmic agents in maintaining the sinus
rhythm after cardioversion of atrial fibrillation16.
The analysis of available studies evidenced that
among these drugs only propafenone and amiodarone did not differ from placebo as for proarrhythmic effect16. In particular, when comparing propafenone and flecainide, a marked difference in Odd’s Ratios was seen, as reported in
Table V16.
The available evidence allows concluding
that propafenone can be an effective therapeutic
measure in the management of atrial fibrillation,
in both approaches: the acute treatment, for
conversion of sinus rhythm, and the chronic
treatment, for maintenance and prevention of
atrial fibrillation recurrences, with a good safety
profile.
As for administration schemes (described in
the data sheet for prescriber information) 37 ,
propafenone allows proper therapeutic schedules
for acute treatment through two formulations, solution for intravenous use and immediate-release
tablets, while the sustained-release capsules represent the ideal bid presentation for maintaining
sinus rhythm, with a favourable impact on compliance and adherence of patients to the therapy.
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