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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 Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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 Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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 Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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, % Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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. Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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. Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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 Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 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. References 1. 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ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257–e354. 3. Meiltz A, Zimmermann M, Urban P, Bloch A; Association of Cardiologists of the Canton of Geneva. Atrial fibrillation management by practice cardiologists: a prospective survey on the adherence to guidelines in the real world. Europace. 2008;10:674–680. 4.Nabauer M, Gerth A, Limbourg T, Schneider S, Oeff M, Kirchhof P, Goette A, Lewalter T, Ravens U, Meinertz T, Breithardt G, Steinbeck G. 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Am J Cardiol. 2010;105:687–693. 16. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH; European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–2429. 17. Wyse DG. Lenient versus strict rate control in atrial fibrillation some devils in the details. J Am Coll Cardiol. 2011;58:950–952. 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 Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017 Circ Arrhythm Electrophysiol. 2012;5:632-639; originally published online July 11, 2012; doi: 10.1161/CIRCEP.112.970749 Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2012 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-3149. 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