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Distribution and Risk Profile of Paroxysmal, Persistent, and
Permanent Atrial Fibrillation in Routine Clinical Practice
Insight From the Real-Life Global Survey Evaluating Patients With
Atrial Fibrillation International Registry
Chern-En Chiang, MD, PhD; Lisa Naditch-Brûlé, MD; Jan Murin, MD; Marnix Goethals, MD, PhD;
Hiroshi Inoue, MD, PhD; James O’Neill, MD; Jose Silva-Cardoso, MD, PhD; Oleg Zharinov, MD, PhD;
Habib Gamra, MD; Samir Alam, MD; Piotr Ponikowski, MD, PhD; Thorsten Lewalter, MD;
Mårten Rosenqvist, MD, PhD; Philippe Gabriel Steg, MD
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Background—There is a paucity of international data on the various types of atrial fibrillation (AF) outside the highly selected
populations from randomized trials. This study aimed to describe patient characteristics, risk factors, comorbidities,
symptoms, management strategy, and control of different types of AF in real-life practice.
Methods and Results—Real-life global survey evaluating patients with atrial fibrillation (RealiseAF) was a contemporary,
large-scale, cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months.
Investigators were randomly selected to avoid bias. Among 9816 eligible patients from 831 sites in 26 countries, 2606
(26.5%) had paroxysmal, 2341 (23.8%) had persistent, and 4869 (49.6%) had permanent AF. As AF progressed from
paroxysmal to persistent and permanent forms, the prevalence of comorbidities, such as heart failure (32.9%, 44.3%, and
55.6%), coronary artery disease (30.0%, 32.9%, and 34.3%), cerebrovascular disease (11.7%, 10.8%, and 17.6%), and
valvular disease (16.7%, 21.2%, and 35.8%), increased, and the prevalence of lone AF decreased. Similarly, there was an
increase in mean CHADS2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score (1.7, 1.8, and 2.2), and
more than half of patients (51.0%, 56.7%, and 67.3%) qualified for oral anticoagulants. Almost 90% of patients received
≥1 antiarrhythmic drug, but >60% had European Heart Rhythm Association symptom scores from II to IV. Furthermore,
40.7% of persistent and 49.8% of permanent AF patients were still in AF with a heart rate >80 beats per minute.
Conclusions—This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type
of AF, especially those with the permanent form. (Circ Arrhythm Electrophysiol. 2012;5:632-639.)
Key Words: antiarrhythmia agents ◼ atrial fibrillation ◼ epidemiology ◼ heart failure ◼ risk factors
A
trial fibrillation (AF) is the most common sustained
cardiac arrhythmia and carries an increased risk of
stroke, hospitalization, and mortality. The various types of
AF (paroxysmal, persistent, or permanent) may differ in
terms of clinical characteristics and comorbidities, affecting the management strategy and long-term outcomes.1 It
is important to characterize the cardiovascular risk profiles
in patients with permanent AF in comparison with patients
with paroxysmal or persistent AF.2
Clinical Perspective on p 639
Although information regarding the risk profiles of
these various AF subtypes has been reported, most of this
information stems from a single country3,4 or from Europe1,5
or North America6 or excludes patients with permanent AF.7
On the other hand, populations enrolled in clinical trials tend
to be highly selected and may not reflect patients encountered
in routine clinical practice.8 Furthermore, the clinical
Received January 15, 2012; accepted June 19, 2012.
From the General Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
(C-E.C.); Sanofi, Paris, France (L.N-B.); Department of Internal Medicine and Cardiology, Comenius University, Bratislava, Slovakia (J.M.); Department
of Cardiology-Electrophysiology, H.-Hartziekenhuis Roeselare-Menen, Roeselare, Belgium (M.G.); Second Department of Internal Med, University of
Toyama, Toyama, Japan (H.I.); Connolly/Mater Hospitals/RCSI, Dublin, Ireland (J.O.); Department of Cardiology, Porto Medical School, Hospital S.
João, Porto, Portugal (J.S-C.); National Medical Academy of Postgraduate Education, Kiev, Ukraine (O.Z.); Cardiology A Department, Cardiothrombosis
Research Unit, Fattouma Bourguiba University Hospital, Monastir, Tunisia (H.G.); Division of Cardiology, American University of Beirut Medical Centre,
Beirut, Lebanon (S.A.); Department of Heart Disease, Medical University, Wroclaw, Poland (P.P.); Academic Hospital, University of Bonn, Bonn, Germany
(T.L.); Karolinska Institute, Södersjukhuset, Stockholm, Sweden (M.R.); and INSERM U-698, Paris, France, Université Paris-Diderot, Paris, France, and
Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Bichat-Claude Bernard, Paris, France (P.G.S.).
Presented, in part, at the Annual Meeting of European Society of Cardiology, Paris, France, August 29, 2011.
Correspondence to Chern-En Chiang, MD, PhD, General Clinical Research Center, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Rd, Taipei
112, Taiwan. E-mail [email protected]
© 2012 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org
632
DOI: 10.1161/CIRCEP.112.970749
Chiang et al Differences in Risk in the RealiseAF 633
management and epidemiology of AF have been changing
rapidly. We need a contemporary, cross-sectional, and
international survey of different types of AF to describe their
risk profiles and management strategy and to provide further
insight of patients with AF in our routine daily practice.
The Real-life global survey evaluating patients with atrial
fibrillation (RealiseAF) survey was established to describe
patient characteristics, cardiovascular risk, types of AF, symptoms, medical history, and management strategies in real-life
practice.9
Methods
Design
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As previously published,9 RealiseAF was a cross-sectional observational survey of >10 000 patients with AF seen at >800 sites in
26 countries from October 2009 to May 2010. Participating countries
were Algeria, Azerbaijan, Belgium, Bulgaria, Czech Republic, Egypt,
Germany, Hungary, India, Ireland, Italy, Lebanon, Lithuania, Mexico,
Morocco, Portugal, Russia, Slovakia, Spain, Sweden, Switzerland,
Taiwan, Tunisia, Turkey, Ukraine, and Venezuela.
Results
RealiseAF included 10 546 patients from 831 sites in 26 countries on 4 continents. Participating physicians were 83.1% cardiologists, 7.8% internists, and 9.1% physicians who defined
themselves as both a cardiologist and an internist. Excluding
23 ineligible patients, 675 patients who had a first episode of
AF, and 32 patients with missing data on the type of AF, there
were 9816 patients eligible for the current analysis, of whom
2606 (26.5%) had paroxysmal, 2341 (23.8%) persistent, and
4869 (49.6%) permanent AF.2 Baseline characteristics are
shown in Table 1. Mean age was highest in patients with permanent AF, who also had the longest duration of AF since
diagnosis. There were more men than women in all groups
(Table 1).
Cardiovascular Risk Factors and Comorbidities
Patients with a history of AF (treated or not, and whatever the rhythm
was at the time of inclusion), with at least 1 AF episode documented
by standard ECG or by Holter-ECG in the previous 12 months, or
documented current AF, who provided written, informed consent,
were enrolled. Exclusion criteria were limited to mental disability
(such as dementia or significant cognitive disorders), inability to provide written, informed consent, postoperative AF within 3 months of
cardiac surgery, and participation in clinical trials investigating AF or
antithrombotics during the previous month.
Patients with AF had multiple cardiovascular risk factors, as
shown in Table 2. Hypertension was the most common, followed
by physical inactivity and dyslipidemia. Approximately a
fifth of the patients had diabetes mellitus across the various
AF subsets. Although hypertension and dyslipidemia were
slightly less frequent in patients with permanent AF than
in those with paroxysmal AF, patients with permanent
AF had more comorbidities (Table 3). The prevalence of
comorbidities, particularly heart failure, coronary artery
disease, cerebrovascular disease, valvular heart disease, and
chronic pulmonary disease, increased in a stepwise fashion
from paroxysmal to persistent to permanent AF. Similarly, the
prevalence of lone AF decreased from paroxysmal to persistent
and permanent AF.
Selection of Investigators
Distribution of CHADS2 Score
Patients
Participating physicians were randomly selected from a global list
of cardiologists and internists (office- and hospital-based) in each
country in 2009 to 2010. The ratio of cardiologists to internists was
predetermined to reflect the practice in each country so that unbiased recruitment could be achieved. The list and ratio were validated
by national coordinators. The maximum duration of enrolment per
center was 6 weeks to maximize recruitment of consecutive patients.
Each investigator was asked to recruit a minimum of 10 patients and
a maximum of 30.
The distribution of CHADS2 scores across the various types of
AF is shown in Table 4. The mean CHADS2 score increased,
as did the proportion of patients with a CHADS2 score ≥2,
as AF progressed from paroxysmal to permanent. Among
patients meeting criteria for anticoagulation (CHADS2 ≥2),
the percentage of patients actually receiving oral anticoagulant (OAC) was 37.7%, 54.4%, and 59.0% for paroxysmal,
persistent, and permanent AF, respectively (P<0.0001).
Objectives
Use of Antiarrhythmic Drugs
The primary objectives of this analysis were to describe the clinical
characteristics, risk factors and comorbidities, management strategy,
and control of AF in patients with paroxysmal, persistent, or permanent AF. Control of AF was defined as either being in sinus rhythm on
an ECG or being in AF with a resting ventricular rate ≤80 beats per
minute on resting ECG at the time of the visit. A post hoc sensitivity
analysis was also performed to evaluate the proportion of patients in
AF with a ventricular rate ≥110 beats per minute.10
Figure 1 shows use of antiarrhythmic drugs (AADs) in
different types of AF. More than 80% of patients received
at least 1 AAD. Class Ia drugs were rarely used. Class Ic
drugs, such as propafenone, flecainide, and sotalol, were
more commonly used in patients with paroxysmal AF.
Amiodarone was more frequently used for persistent AF.
Interestingly, 12% of patients with permanent AF received
amiodarone, presumably as a rate-control agent. Class II
and IV drugs, as well as cardiac glycosides, were more
commonly prescribed in patients with permanent AF as
rate-control agents.
Statistical Analysis
The details of the determination of sample size have been described
previously.9 Population characteristics were summarized as mean and
SD for continuous variables and as count and percentages for qualitative variables. Comparisons between subgroups were made using the
χ2 test, Fisher exact test for nominal variables, trend test for ordinal
variables, or ANOVA for quantitative variables. Analyses were performed using the SAS statistical software, version 9.1 (SAS Institute,
Cary, NC).
Coprescription of Medications
Figure 2 shows the distribution of the use of medications
across all groups. The use of diuretics, nitrates, angiotensinconverting enzyme inhibitors, and antidiabetic drugs were
634 Circ Arrhythm Electrophysiol August 2012
Table 1. Baseline Characteristics According to Types of AF
Patients, n (%)
Paroxysmal
Persistent
Permanent
P Value
2606 (26.5)
2341 (23.8)
4869 (49.6)
NA
Age in y, mean (SD)
64.7 (12.4)
66.0 (11.8)
68.3 (11.8)
<0.0001
≥75 y, %
22.4
25.3
32.8
<0.0001
55.8
0.18
Male, %
55.5
57.9
Systolic blood pressure, mm Hg, mean (SD)
133.8 (19.5)
132.7 (19.5)
132.4 (19.0)
Diastolic blood pressure, mm Hg, mean (SD)
79.7 (10.9)
80.3 (11.2)
79.6 (11.5)
0.0110
0.0413
Heart rate, bpm, mean (SD)
77.0 (24.6)
83.1 (24.3)
84.0 (19.7)
<0.0001
BMI, kg/m2, mean (SD)
28.0 (5.0)
28.7 (5.3)
28.3 (5.3)
<0.0001
White
81.2
88.9
84.0
Black
<0.1
<0.1
0.1
Asian
Ethnicity, %
<0.0001
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13.1
6.4
10.0
Hispanic
3.3
2.3
4.3
Others
2.5
2.4
Time since AF diagnosis, mo, mean (SD)
1.5
39.9 (60.3)
34.1 (54.0)
76.5 (79.1)
25.6
26.8
5.8
3–6 mo
8.2
10.1
3.6
6–12 mo
12.5
13.4
7.7
>12 mo
53.7
49.7
82.8
<0.0001
Duration, %
<0.0001
<3 mo
AF indicates atrial fibrillation; NA, not applicable; bpm, beats per minute; BMI, body mass index.
more common as patients progressed from paroxysmal to persistent and permanent AF.
permanent AF, whereas dyspnea and fatigue were less prevalent in patients with paroxysmal AF. The vast majority of
Symptoms
Table 3. Comorbidities in Patients With Different Types of AF
Despite the fact that almost 90% of patients had received
at least 1 AAD during the previous 7 days, symptom
relief was poor; ≈60% of patients across all groups had
at least 1 symptom during the last week before the visit
(Table 5). Palpitations were less common in patients with
At least 1 comorbidity, %
69.3
75.7
84.8
<0.0001
Heart failure, %
32.9
44.3
55.6
<0.0001
No HF or NYHA I
72.7
62.0
50.3
NYHA II
20.0
24.3
29.5
7.3
13.7
20.2
Table 2. Cardiovascular Risk Factors in Patients With
Different Types of AF (%)
Heart failure in class, %
NYHA III–IV
Paroxysmal Persistent Permanent P Value
Hypertension
74.6
73.2
71.6
0.0173
Diabetes mellitus
19.1
19.3
23.5
<0.0001
Dyslipidemia
50.4
48.2
44.4
<0.0001
Current smoker
10.3
11.2
9.0
0.0112
Obesity (BMI ≥30 kg/m2)
30.9
35.0
32.4
0.0100
Physical inactivity
53.9
59.9
65.1
<0.0001
Family history of premature
cardiovascular death
26.0
24.1
21.7
0.0005
Family history of premature
sudden death
6.4
6.6
5.7
77.3
77.7
79.2
Left ventricular ejection
fraction within past 12 mo
in %, n mean (SD)
P Value
<0.0001
1975
1892
3481
<0.0001
58.5 (10.7) 54.3 (12.1) 53.3 (12.2)
Left ventricular hypertrophy
(ECG), %
12.3
12.7
14.6
Coronary artery disease, %
30.0
32.9
34.3
0.0009
Cerebrovascular disease, %
11.7
10.8
17.6
<0.0001
Valvular heart disease, %
16.7
21.2
35.8
<0.0001
Chronic pulmonary
disease, %
9.4
8.9
12.9
<0.0001
Liver diseases, %
4.5
3.9
4.9
0.16
0.32
Chronic advanced renal
failure, %
3.5
3.9
4.3
0.22
0.12
Lone AF*, %
9.3
5.3
2.0
<0.0001
Smoking
≥3 cardiovascular risk factors*
Paroxysmal Persistent Permanent
AF indicates atrial fibrillation; BMI, body mass index.
*Cardiovascular risk factor used for this calculation included age >50 for
men/>65 for women, family history of premature cardiovascular disease,
family history of premature sudden death, current smoker, no physical activity,
obesity, arterial hypertension, diabetes mellitus, and dyslipidemia.
0.0117
AF indicates atrial fibrillation; HF, heart failure; NYHA, New York Heart
Association.
*Defined as patients aged <60 y with no coronary artery disease/heart failure/
valvular heart disease/chronic pulmonary disease/venous thromboembolism/
arterial hypertension.
Chiang et al Differences in Risk in the RealiseAF 635
Table 4. Distribution of CHADS2 Score Across Different Types
of AF
Paroxysmal
Mean, (SD)
CHADS2 ≥2, %
1.7 (1.3)
Persistent
1.8 (1.3)
Permanent
P Value
2.2 (1.3)
<0.0001
67.3
<0.0001
Control of AF
The percentage of patients with uncontrolled AF (defined as
being in AF with a ventricular rate >80 beats per minute) was
19.8%, 40.7%, and 49.8% for paroxysmal, persistent, and permanent AF, respectively (P<0.0001) (Figure 4). When a ventricular rate ≥110 beats per minute was used, the percentages
were 10.1%, 15.2%, and 10.8%, respectively (P<0.0001).
51.0
56.7
0
16.0
13.6
9.0
1
32.9
29.7
23.7
Management Strategies
2
28.8
31.8
31.4
3
13.1
15.4
20.2
4
5.3
5.5
10.2
5
3.1
3.6
4.4
6
0.7
0.5
1.1
Management strategies before and after the visit are shown
in Table 6. Rhythm-control strategy was applied in >50% of
patients with paroxysmal or persistent AF before the visit.
Interestingly, there were still 9% of patients with permanent
AF in whom the investigators settled on a rhythm-control
strategy. After the study visit, there was a decrease in the proportion of patients in whom no clear strategy was selected (neither rhythm-control nor rate-control strategy). More patients
with paroxysmal or persistent AF experienced changes in their
management strategies (17.7% and 24.4%, respectively) than
patients with permanent AF (8.5%).
Distribution, %
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CHADS2 score indicates a measure of the risk of stroke in which congestive
heart failure, hypertension, an age of >75 y, and diabetes mellitus are each
assigned 1 point and previous stroke or transient ischemic attack is assigned 2
points; AF, atrial fibrillation.
patients had European Heart Rhythm Association (EHRA)
symptom scores from II to IV (two thirds of patients with
paroxysmal AF, three quarters of patients with persistent and
permanent AF).
Hospitalizations
Up to ≈30% of patients had experienced at least 1 admission
because of a cardiovascular event in the past 12 months
(Figure 3). Acute decompensation of heart failure was the
leading cause in persistent and permanent AF. Stroke rates
were higher for patients with persistent than paroxysmal AF
and highest in patients with permanent AF. In turn, arrhythmic
or proarrhythmic events were most frequent in patients with
paroxysmal AF. Up to 12.3% of patients with paroxysmal AF
had at least one such event.
Discussion
The RealiseAF survey provides a unique opportunity to
examine the risk profile and management of different types of
AF in daily practice on an international basis. We found that as
AF progressed from paroxysmal to persistent and permanent
forms, there was an increase in the prevalence of comorbidities,
the risk of thromboembolism, and acute decompensation of
heart failure. Patients became more frequently symptomatic,
and AF was less frequently controlled (at least when AF
control was defined with a stringent heart rate <80 beats per
minute).
Studies of paroxysmal or persistent AF are common.7
However, studies of the full spectrum of AF, including
permanent AF, are more scarce.5 The Euro Heart Survey
Figure 1. The distribution of antiarrhythmic drug (AAD) use at the time of the visit in different types of atrial fibrillation (AF). *Prescribed for
AF indication.
636 Circ Arrhythm Electrophysiol August 2012
Figure 2. Coprescription of medications at the time of the visit in different types of atrial fibrillation. ACE indicates angiotensin-converting
enzyme.
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on AF described AF management for different types of AF
in European countries, in which the national coordinator
from each country supplied a list of centers that would
be suitable to participate in the survey.5 The authors
noted that they may have had an overrepresentation of
highly specialized and AF-interested centers.5 In contrast,
RealiseAF was an international survey comprising data
from 26 countries across 4 continents, and investigators
were randomly selected, suggesting it represents a valid
global contemporary survey of full-spectrum AF in common
clinical practice.
RealiseAF did not enroll patients from Canada or the
United States, but its results are highly consistent with those
from a large North American cross-sectional study describing
prevalence and risk factors of AF.6 The prevalence of comorbidities, such as heart failure (29.2%), coronary artery disease (34.6%), and diabetes mellitus (17.1%), in AF patients
in their study, which also enrolled black patients, was high
and similar to those reported in RealiseAF.
Table 5. Symptoms and EHRA Score in Patients with
Different Types of AF (%)
Paroxysmal Persistent
Permanent
P Value
Symptoms in the week before the visit (including the day of the visit)
At least 1 symptom
59.9
62.3
59.0
0.0296
Palpitations
37.5
36.2
29.2
<0.0001
Dyspnea
32.1
41.8
41.6
<0.0001
Fatigue
30.9
37.8
36.4
<0.0001
Light headedness/
dizziness
16.2
14.8
15.0
0.28
Chest pain
17.5
14.6
14.1
0.0003
2.5
1.8
1.5
0.0076
Syncope
EHRA score at the visit
<0.0001
I
34.5
23.8
22.9
II
50.0
53.0
52.3
III
14.7
21.3
22.4
IV
0.8
1.9
2.4
65.5
76.2
77.1
II to IV at the day of the visit
<0.0001
EHRA indicates European Heart Rhythm Association; AF, atrial fibrillation.
Patient Characteristics, Risk Factors,
and Comorbidities
Generally, patients enrolled in clinical trials are highly
selected and are at lower risk of adverse outcomes than
patients from routine practice, which limits the external
validity of clinical trials. Interestingly, the prevalence of
comorbidites in RealiseAF was quite similar to that observed
in recent large clinical trials. In the ATHENA (A PlaceboControlled, Double-Blind, Parallel Arm Trial to Assess the
Efficacy of Dronedarone 400 mg BID for the Prevention of
Cardiovascular Hospitalization or Death from Any Cause in
Patients with Atrial Fibrillation/Atrial Flutter) trial, which
enrolled patients with paroxysmal or persistent AF aged at
least 70 years,11 there were 21.1% of patients with heart failure New York Heart Association II or III. In RealiseAF, the
percentages of patients with heart failure New York Heart
Association II to IV were 27.3% for patients with paroxysmal AF and 38.0% for patients with persistent AF. Clearly,
RealiseAF had more patients with moderate to severe heart
failure than the ATHENA trial. Again, 30.4% of patients in
ATHENA had coronary artery disease, whereas in RealiseAF,
30.0% of patients with paroxysmal AF and 32.9% with persistent AF had coronary artery disease. In the Atrial Fibrillation
Follow-up Investigation of Rhythm Management (AFFIRM)
trial,8 there were only 23.1% of patients with heart failure and
26.1% of patients with coronary artery disease, which were
less than in RealiseAF. Our findings confirm the high cardiovascular risk of AF patients seen in daily practice. As AF progressed from paroxysmal to persistent and permanent forms,
there was a concomitant increase in the cardiovascular risk
profile. The risk of patients in permanent AF is of particular
concern because 84.8% of patients had at least 1 comorbidity.
CHADS2 Score
The CHADS2 scores were higher than previously reported
in patients with AF in real-life practice.3,4 The percentage of
patients with CHADS2 scores ≥2, that is, who had clear-cut
indications for OAC therapy, was 51.0%, 56.7%, and 67.3%
among patients with paroxysmal, persistent, and permanent
AF, respectively. The distribution of CHADS2 scores in
patients with permanent AF in the RealiseAF survey was quite
similar to that seen in recent antithrombotic trials in AF.12,13
Chiang et al Differences in Risk in the RealiseAF 637
Figure 3. Cardiovascular events leading to hospitalization in the previous 12 months in different types of atrial fibrillation. CNS indicates
central nervous system; CV, cardiovascular.
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The mean (SD) CHADS2 score of 2.2 (1.3) in RealiseAF was
similar to the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY)12 and Apixaban for Reduction In
STroke and Other ThromboemboLic Events in atrial fibrillation (ARISTOTLE) trials13 (scores of 2.1 [1.1] and 2.1 [1.1],
respectively). Of interest, there was a marked underuse of
OACs in RealiseAF, as has been seen in other studies.14
Symptoms
About 60% of patients with AF complained of symptoms.
Interestingly, palpitation was not necessarily the most common symptom. In patients with persistent and permanent AF,
dyspnea and fatigue were more frequently reported. When
an EHRA symptom score ≥II was considered, patients with
paroxysmal AF were less symptomatic than patients with
permanent AF. Because symptoms predicted an adverse outcome independent of associated cardiovascular disease in a
recent study of AF,7 we may need to reconsider the clinical
significance of symptoms associated with AF, beyond their
relevance to quality of life. On the other hand, AADs were not
effective in ameliorating symptoms: almost 90% of patients in
RealiseAF received at least 1 AAD, yet prevalence of symptoms was high.
Management Strategy and Control of AF
Although a rhythm-control strategy has not been shown to be
superior to a rate-control strategy in reducing cardiovascular events in patients with nonpermanent AF, it is still more
commonly used.5,15,16 This was also the case in RealiseAF. We
also found that there was a change in strategy among 17.7%
of patients with paroxysmal AF and 24.4% of patients with
persistent AF, mainly because of an increase in the rhythmcontrol strategy and a decrease in the proportion of patients in
whom no clear strategy was declared.
The RACE II trial [RAte Control Efficacy in permanent
atrial fibrillation] suggested noninferiority of lenient compared with strict rate control.10 However, RealiseAF was
designed before publication of these results.7,17 Therefore,
control of AF in the RealiseAF survey was defined as either
being in sinus rhythm or being in AF with a resting ventricular
rate ≤80 beats per minute. Although there were only 10.8%
of permanent AF patients who had uncontrolled AF (a ventricular rate ≥110 beats per minute) based on a lenient-control
strategy, 77.1% of them were symptomatic according to their
EHRA score.
A hierarchical model would be the best way to control for
random variation across sites and countries. Any association
may be confounded by factors, including but not limited to
differences in diagnosis, access to cases, and ethnicity. Most
of the data presented in this article were descriptive in nature,
without inferring associations. A single-level model, as used
in the present study, may be sufficient.
Limitations
The present report should be interpreted cautiously, given its
observational and cross-sectional nature. Despite the wide
Figure 4. Control of atrial fibrillation (AF) at the time of the visit (based on ECG) in different types of AF (P<0.001). *Defined as being in
sinus rhythm or in AF with heart rate (HR) ≤80 beats per minute.
638 Circ Arrhythm Electrophysiol August 2012
Table 6. Changes of AF Management Strategy After the Visit
in Different Types of AF
Paroxysmal
Persistent
Permanent
Before the visit, %
Rhythm control
67.8
51.9
9.0
Rate control
18.8
37.0
84.2
None
13.3
10.8
6.8
Both
<0.1
0.2
Rhythm control
73.8
55.7
7.2
Rate control
0
After the visit, %
<0.0001
19.6
39.3
88.3
None
6.5
4.5
4.3
Both
0.1
0.5
0.2
Change of management
strategy, %
Yes
P Value
<0.0001
<0.0001
17.7
24.4
8.5
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AF indicates atrial fibrillation.
geographic scope of this study, it does not include Central
Africa or the United States and Canada. There are likely major
differences in patient characteristics and management in these
regions. However, RealiseAF has unprecedented geographic
relevance by including many developing low- and middleincome countries.
Conclusions
RealiseAF is an international survey of different types of AF
in daily practice and provides a snapshot of real-world data
regarding the risk level and AF management strategy on a
global basis. About half of all patients had permanent AF,
whereas paroxysmal and persistent AF equated a quarter each.
Risk factors and comorbidities were common and similar to
those in clinical trials. The prevalence of moderate to severe
heart failure, coronary artery disease, diabetes mellitus, and
cerebrovascular disease increased from paroxysmal to permanent AF. More than half of all patients with AF qualified for
the use of OACs, but OACs were inadequately used. AADs
were not effective in reducing symptoms or in maintaining
sinus rhythm. The RealiseAF survey disclosed high cardiovascular risks and an unmet need in our daily practice in patients
with AF, especially the permanent form.
Acknowledgments
We acknowledge the assistance of Sandrine Brette (Lincoln, under
contract with Sanofi) for the statistical analyses and Sola Neunie,
MSc (PPSI, UK) for the editing of the manuscript, references, and
figures, supported by Sanofi.
Sources of Funding
Funding for the RealiseAF survey was provided by Sanofi, Paris,
France.
Disclosures
Dr Chiang has received Honoraria for lectures from AstraZeneca,
Merck Sharp & Dome, Novartis, Pfizer, Sanofi, Daichi-Sankyo,
Bayer, Boehringer Ingelheim, Roche, Servier, Tanabe, and
Takeda. Dr Naditch-Brûlé is an employee of Sanofi. Dr Murin has
received consultancy fees from Sanofi and Boehringer Ingelheim
and congress fees from Pfizer, Richter Gedeon, and Abbott. Dr
Goethals has received consulting fees from Sanofi, Bayer, and
Boehringer Ingelheim. Dr Inoue has received honoraria from
Daiichi Sankyo, Sanofi, and Eisai. Dr O’Neill has received honoraria and lecture fees from Sanofi, AstraZeneca, Novartis, and
Bayer. Dr Silva-Cardoso has received consulting fees and lecture
fees from Abbott, AstraZeneca, Menarini, Merck, Merck Sharp &
Dohme, Novartis, Pfizer, and Sanofi. Dr Zharinov has received
consultancy fees and honoraria from Sanofi. Dr Gamra has received consulting fees from Sanofi. Dr Alam has nothing to disclose. Dr Ponikowski has received consulting fees and lecture fees
from Sanofi and Merck Sharp & Dohme. Dr Lewalter has received
lecture fees from Sanofi. Dr Rosenqvist has received consulting
fees from Medtronic, Sanofi, Merck, Sharp & Dohme, Boehringer
Ingelheim, Bayer, and Bristol-Myers Squibb. Dr Steg has received
research grants from Servier; consultancy fees/honoraria from
Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim,
Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly alliance, Eisai,
GlaxoSmithKline, Medtronic, Merck Sharpe & Dohme, Pfizer,
Roche, Sanofi, Servier, and The Medicines Company; and has
equity ownership in Aterovax.
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CLINICAL PERSPECTIVE
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Real-life global survey evaluating patients with
atrial fibrillation (RealiseAF) is an international survey of 9816 patients with AF from 831 sites in 26 countries. Most previous studies stem from data from a single country or from Europe or North America or exclude permanent AF patients. In
addition, data from patients enrolled in clinical trials are often highly selected and fail to represent patients encountered in
routine clinical practice. Furthermore, clinical practice and the epidemiology of AF have been changing rapidly. RealiseAF
represents a contemporary, cross-sectional survey of different types of AF in daily practice that provides a global snapshot of
real-world data regarding AF risk and AF management strategy. When AF progressed from paroxysmal to persistent and permanent forms, it was found that there was an increase in the prevalence of comorbidities and the risk of thromboembolism,
similar to or higher than those in patients enrolled in clinical trials. Patients became more symptomatic, and the AF became
less controlled. This survey disclosed high cardiovascular risk and an unmet need in daily practice for patients with any type
of AF but especially those with the permanent form. In the turmoil after the PALLAS trial [Permanent Atrial fibriLLAtion
outcome Study using Dronedarone on top of standard therapy], the data from the RealiseAF survey are extremely important
for the understanding of the risk level in patients with permanent AF and for the design of clinical trials for AF in the future.
To the best of our knowledge, the RealiseAF survey is the largest and most comprehensive survey in AF and thus is highly
relevant to clinical practice.
Distribution and Risk Profile of Paroxysmal, Persistent, and Permanent Atrial Fibrillation
in Routine Clinical Practice: Insight From the Real-Life Global Survey Evaluating
Patients With Atrial Fibrillation International Registry
Chern-En Chiang, Lisa Naditch-Brûlé, Jan Murin, Marnix Goethals, Hiroshi Inoue, James
O'Neill, Jose Silva-Cardoso, Oleg Zharinov, Habib Gamra, Samir Alam, Piotr Ponikowski,
Thorsten Lewalter, Mårten Rosenqvist and Philippe Gabriel Steg
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Circ Arrhythm Electrophysiol. 2012;5:632-639; originally published online July 11, 2012;
doi: 10.1161/CIRCEP.112.970749
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