Cochrane Database of Systematic Reviews

Antiarrhythmics for maintaining sinus rhythm after

cardioversion of atrial fibrillation (Review)

Lafuente-Lafuente C, Valembois L, Bergmann JF, Belmin J

Lafuente-Lafuente C, Valembois L, Bergmann JF, Belmin J.

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.
Cochrane Database of Systematic Reviews 2015, Issue 3. Art. No.: CD005049.
DOI: 10.1002/14651858.CD005049.pub4.

www.cochranelibrary.com

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Figure 7. Withdrawals due to adverse events and pro-arrhythmia.

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation (Review) 15
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
All studied antiarrhythmics showed increased pro-arrhythmic
effects (counting both bradyarrhythmias and tachyarrhythmias
attributable to treatment) with the exceptions of amiodarone,
dronedarone and propafenone (Analysis 3.1). Pooled event rates
varied depending on the antiarrhythmic used: from 4% to 23% for
withdrawals due to adverse effects, and from 1% to 12% for pro-
arrhythmia. The NNTH, the mean number of patients needed
to treat for 1 year to have 1 excess withdrawal due to adverse ef-
fects from treatment were 9 with quinidine, 15 with sotalol, 22
with dronedarone and 26 with amiodarone or propafenone. The
NNTH for pro-arrhythmia was 38 with flecainide and sotalol, 85
with quinidine and 156 with dofetilide.
Ventricular arrhythmias (torsades, ventricular tachycardia (VT),
ventricular fibrillation (VF), widening QRS or QT leading to
stopping treatment, sudden death or unexplained syncope) were
the most frequent pro-arrhythmic events reported with dofetilide
(100% of all pro-arrhythmic events), quinidine (94%) and fle-
cainide (69%), while symptomatic bradyarrhythmias (sinus brady-
cardia leading to stopping treatment, atrio-ventricular (AV) block)
were more frequent with metoprolol (94% of all events) and amio-
darone (69%). Others drugs demonstrated both types of pro-
arrhythmic events: propafenone (63% ventricular events, 39%
bradycardia), sotalol (61% ventricular events, 39% bradycardia)
and dronedarone (41% ventricular events, 59% bradycardia).
In direct comparisons between antiarrhythmics (Analysis 2.6 and
Analysis 3.6), quinidine caused more withdrawals than the other
class I drugs (OR 2.25, 95% CI 1.45 to 3.51, P = 0.0003) but not
more pro-arrhythmia. Amiodarone produced significantly fewer
withdrawals (OR 0.55, 95% CI 0.36 to 0.84, P = 0.006) and
fewer pro-arrhythmic events (OR 0.28, 95% CI 0.13 to 0.59, P
= 0.0007) than class I drugs combined. However, compared to
placebo, amiodarone had a high OR for increasing withdrawals
(OR 5.55, 95% CI 2.24 to 13.7). Significant heterogeneity be-
tween the studies comparing two antiarrhythmic drugs was found
Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
in the analysis of withdrawals. This heterogeneity was probably
explained by the differences in criteria for stopping treatment and
withdrawal of patients when adverse effects appeared.
Sensitivity analysis did not modify the results for withdrawals and
pro-arrhythmia.
Stroke
Results for stroke are summarised in Analysis 4.1. Only 11
of the 42 studies with a control group (placebo or no treat-
ment arm) reported stroke outcomes (ATHENA 2009; Benditt
1999; Carunchio 1995; EURIDIS ADONIS 2007; Flec-SL
2012; Hillestad 1971; Karlson 1998; Lloyd 1984; SAFE-T 2005;
Sodermark 1975; SOPAT 2004) and we were uncertain that re-
porting of stroke was complete. The reported stroke rate was very
low (1% to 2% at 1 year). No significant difference appeared be-
tween antiarrhythmic drugs and controls except for dronedarone,
which showed a significant association with reduced risk of stroke
(OR 0.66, 95% CI 0.46 to 0.95, P = 0.02). This result, however,
was due to a single large study, the ATHENA trial, where stroke was
significantly less frequent in the group treated with dronedarone
(1.2% per year) than in the placebo group (1.8% per year). The
other studies on dronedarone either did not show any difference
compared with the control group or did not report stroke.
Atrial fibrillation recurrence
Results for atrial fibrillation recurrence are summarised in Analysis
5.1 and Figure 8. All class IA, class IC and class III drugs included
in this review significantly reduced the recurrence of atrial fibrilla-
tion. Metoprolol, based on two studies (562 patients), also showed
a significant effect in reducing the number of recurrences of atrial
fibrillation (OR 0.62, 95% CI 0.44 to 0.88, P = 0.008). In con-
trast, class IB drugs did not show any difference compared with
control.
16