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Arrhythmia Management
Table 1: Trial Design and Characteristics of the Six Trials Included in the Meta-analysis
Study, Year n Population Treatment Arms Duration Specified End-point Documentation of AF Quality
Score*
Tveit, 2004
3
114 AF >48 hours 40mg pravastatin 6 weeks Recurrence of AF Clinical follow-up with ECG 2
and scheduled EC versus standard therapy (primary end-point)
MIRACL, 2004
4
3,086 Acute coronary 80mg atorvastatin 16 weeks Incidence or recurrence of Clinical follow-up with ECG 5
syndrome versus placebo AF (secondary end-point)
Chello, 2006
5
40 Scheduled coronary 20mg atorvastatin 3 weeks Incidence of post-operative ECG monitoring during 4
bypass surgery versus placebo AF (secondary end-point) ICU stay
Ozaydin, 2006
6
48 Persistent AF and 10mg atorvastatin 3 months Recurrence of AF >10 min 24-hour ambulatory 2
scheduled EC versus standard therapy (primary end-point) ECG monitoring
ARMYDA-3, 2006
7
200 Scheduled cardiac surgery 40mg atorvastatin 30 days Incidence of post-operative ECG monitoring during 5
without history of AF versus placebo AF >5 min (primary end-point) hospital stay and clinical
follow-up with ECG
Dernellis, 2006
8
130 Paroxysmal AF 20–40mg atorvastatin 4 to 6 Recurrence of AF >1 min 48-hour ambulatory 3
versus placebo months (primary end-point) ECG monitoring
* On a scale of 0 to 5. AF = atrial fibrilation; EC = electrical cardioversion; ECG = electrocardiogram; ICU = intensive care unit.
Figure 1: Effect of Statins versus Control on First Episode or of patients with new-onset AF or post-operative AF may explain the lack of
Recurrence of Atrial Fibrillation
significance for this subgroup.
Statin and occurrence of atrial fibrillation (primary or secondary prevention)
Statin versus control
Duration of follow-up in the six studies was variable, and may seem
End-point: incidence or recurrence of atrial fibrillation
relatively short. However, different types of AF have varying times to
Study Year Statin Control Odds Ratio development or onset. In each study patients were appropriately
MRACL 2004 1,539 1,548 0.97
monitored based on the type of AF they had. Recurrences of
Tvet 2004 51 51 1.09
paroxysmal AF or AF after cardioversion frequently occur within the
Dernelis 2005 40 40 0.06
first month, and all of the patients with recurrent AF included in
ARMYDA 3 2006 101 99 0.41
our analysis had a follow-up period longer than one month
Chello 2006 24 24 0.33
Ozaydin 2006 24 24 0.17
(six weeks to six months). Post-operative AF patients were followed for
Total 1,775 1,782 0.39
at least three days and for up to 30 days.
23
The MIRACL study was the
Overall p=0.02 only trial not to show a clear reduction in AF with atorvastatin use,
0.1 0.2 0.5 1 2 5 10 particularly in the subgroup of patients in whom new-onset AF was
Favours statin Favours control
analysed with a relatively short follow-up of 16 weeks. This shorter
duration of follow-up (considering new-onset AF) may explain why a
randomised to placebo or control regimens. Atorvastatin was used in five beneficial effect against AF was not observed with statins in the
of the six studies, but intervention doses were variable. Comparisons were MIRACL study. This relatively inadequate follow-up duration may also
made with placebo (n=4) or a control regimen (n=2). explain the lack of benefit of statin use on the primary prevention of
AF (post-operative AF or new-onset AF) since these results were
Follow-up durations ranged from three to 26 weeks. Coronary artery disease essentially driven by the MIRACL study.
was present in 3,306/3,557 patients (93%). When the Myocardial Ischemia
Reduction with Aggressive Cholesterol Lowering (MIRACL) study was Effect of Statins on Atrial Fibrillation – Possibly
removed, coronary artery disease was present in 219/470 of the patients Not Dose-dependent or Related to Low-density
(47%). Incidence or recurrence of AF occurred in 386 patients: 165/1,775 in Lipoprotein Decrease
patients treated with statin versus 221/1,782 in controls. Overall, the use of Our meta-analysis ignored varying doses of statins and durations of therapy,
statins was associated with a significantly decreased risk of the recurrence as did most of the meta-analyses. We were not able to assess the degree of
of AF compared with control (odds ratio [OR] 0.39, 95% confidence interval low-density lipoprotein (LDL) lowering versus incidence or recurrence of AF
[CI] 0.18–0.85; p=0.02) (see Table 2). The benefit of statin therapy seemed as it was done with other events with statin therapy.
24
We cannot determine
to be more marked in secondary prevention of AF (OR 0.33; p=0.06) than from our analysis whether the benefit was seen because some type or dose
for new-onset or post-operative AF (OR 0.60; p=0.23). When atorvastatin of statins were used or because low LDL levels were achieved. It was not
was considered alone, the benefit was higher (OR 0.30; p=0.01 on the established whether a patient achieved a certain goal of LDL (<100 or
end-point of both incidence or recurrence of AF). Results were similar when <70mg/dl) using moderate-dose statin or whether outcomes would be
ORs were calculated after exclusion of the MIRACL study or when studies better if a higher-dose statin was used. As populations were different, we
with the lowest-quality score were removed. Thus, our analysis suggests that think that, in our meta-analysis, it was rather inappropriate to compare the
the use of statins was significantly associated with a decreased risk of OR in each trial and draw precise conclusions on dose effect. The benefit
incidence or recurrence of AF in patients in sinus rhythm with a history of against AF did not seem to be clearly related to statin dose, particularly for
previous AF undergoing cardiac surgery or after acute coronary syndrome. atorvastatin use as the OR was not lower in the Atorvastatin for Reduction
This beneficial effect appeared more marked in the prevention of AF of Myocardial Dysrhythmia After Cardiac Surgery (ARMYDA-3) and the
recurrences than in the primary prevention of AF, although this is not certain MIRACL studies, in which high doses of atorvastatin were used (40 and
as none of the subset analyses was statistically significant. The lower number 80mg per day, respectively).
94 EUROPEAN CARDIOLOGY
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