Atrial Fibrillation
Saudi Atrial Fibrillation Survey: National, Observational, Cross-sectional Survey Evaluating Atrial Fibrillation Management and the Cardiovascular Risk Profile of Patients With Atrial Fibrillation
Angiology 2015, Vol. 66(3) 244-248 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714529180 ang.sagepub.com
Ahmad Hersi, MBBS, MSc, FRCPC1, Mohammad Abdul-Moneim, MBBS2, Abdulmohsen Almous’ad, MBBS3, Faisal Al-Samadi, MBBS, FRCPC4, Ahmed AlFagih, MBBS5, and Raid Sweidan, MD6
Abstract Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The Saudi Atrial Fibrillation Survey registry was designed to provide epidemiological and clinical data on patients with AF. The registry included 400 consecutive patients who met the eligibility criteria. Control of AF at the time of the initial visit was achieved by 211 (52.75%) patients. Cardiovascular risk profile of the patients with AF was smoking 92 (23.5%), hypertension 253 (63.25%), diabetes 192 (48%), and dyslipidemia 173 (44%). Rate control was the most frequent management strategy (in 265 patients, 66.2%) whereas rhythm control was chosen in 48 (12%) patients. Both strategies were attempted in 5 (1.2%) patients. This is the first nationwide registry of patients with AF in Saudi Arabia. Compared to developed countries, our patients with AF are relatively young and have higher rates of diabetes and rheumatic heart disease. Rate control is the main strategy currently used for managing AF. Keywords Saudi Arabia, atrial fibrillation, survey
Introduction Atrial fibrillation (AF) is the most common encountered arrhythmia.1,2-4 It is quite often associated with comorbidities, particularly ischemic heart disease, valvular diseases, heart failure (HF), diabetes mellitus (DM), and hypertension (HTN).2,5-7 The prevalence of AF continues to rise as the population of the developed countries ages and is expected to show a greater rise in the coming years 3,8,9 Atrial fibrillation is an important cause of morbidity, mortality, and reduced quality of life and a principal cause of hospitalization.8,10,11 Currently, there are 2 main strategies for the management of AF: one is the restoration and maintenance of sinus rhythm (rhythm control) and the other is the control of the ventricular response (rate control). Both rhythm and rate control strategies can be achieved by nonpharmacological as well as pharmacological therapies.12-17 Several randomized clinical trials have been conducted to compare these 2 strategies, and the meta-analysis of these trials showed that rate control and anticoagulation are equivalent to rhythm control strategy. Therefore, treatment guidelines have moved toward rate control and anticoagulation, with rhythm control reserved for highly symptomatic patients.18,19 The characteristics of patients included in rate control versus rhythm control trials are often different than patients treated in
real life.20 Furthermore, data on the management of patients with AF in the Middle East are scarce. Therefore, the Saudi Atrial Fibrillation Survey (SAS) was conducted to compare patients with AF in clinical trials with patients having AF in real-world experience with respect to different management strategies.
Method Study Design The SAS is a multicenter observational cross-sectional study that recruited consecutive patients with AF in 18 centers in 1
Department of Cardiac Sciences, King Saud University, Riyadh, Saudi Arabia Sanofi, Riyadh, Saudi Arabia 3 Cardiology Department, National Guard Hospital, Riyadh, Saudi Arabia 4 Cardiology Department, Prince Salman Heart Center, Riyadh, Saudi Arabia 5 Cardiology Department, Prince Sultan Cardiac Center, Riyadh, Saudi Arabia 6 Cardiology Department, King Fahad Military Hospital, Jeddah, Saudi Arabia 2
Corresponding Author: Ahmad Hersi, Department of Cardiac Sciences, College of Medicine, King Saud University, PO Box 7805 (92), Riyadh, 11472, Saudi Arabia. Email: [email protected]
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Saudi Arabia between April 2011 and November 2011. Each site was asked to recruit a target of 20 to 30 patients. Patients included in the study were aged 18 years with a history of AF (treated or not and whatever the rhythm at inclusion) with at least 1 AF episode documented by standard electrocardiogram (ECG) or by ECG-Holter monitoring in the last 12 months or documented current AF. Patients were asked to participate and sign a written informed consent (obtained from patients or their legal representatives). Those with 1 of the following criteria were excluded from the study: mental disability (including dementia and significant cognitive disorders), unable to understand or sign the written informed consent, postcardiac surgery AF (AF within 3 months after surgery), and participated in a clinical trial in the field of AF or in the field of antithrombotic treatment in the previous month. In order to allow extrapolation of the results to the broadest possible population, patients were recruited from office or hospital-based cardiologists and internists practicing in governmental, private, secondary, and tertiary care centers. The primary objectives of the SAS were to assess the characteristics, management strategies, and outcomes of patients with AF in a real world setting in Saudi Arabia.
Data Collection Data were collected using a paper case report form (CRF) filled by the study investigators. Data collected included the following variables: patient demographics, medical history, stroke risk profile such as congestive HF, age 75, diabetes, stroke, or transient ischemic attack, vascular disease, age 65 to 74 years, sex (female; CHA2DS2-VASc risk score), type of AF (paroxysmal, persistent, permanent, and new onset), management strategy (rhythm control vs rate control), medications use including antiarrhythmic agents, echocardiogram and ECG findings, laboratory investigations, medical therapy, use of cardiac procedures and interventions, and in-hospital outcomes in the past 12 months prior to enrollment. Data entry was carried out by experienced data entry specialists using the Microsoft Access software interface. The study monitor was responsible for solving any correction queries with the survey investigator regarding key variables (by phone, fax, e-mail, or visit). On-site data quality control was performed by study monitors through reviewing the completed CRF for 15% of a random sample of study patients against patient source documents. In addition, another quality control was performed by a data entry supervisor through reviewing the electronic data of a 5% random sample of study patients against the paper CRF.
Statistical Analysis Continuous variables were summarized as mean + standard deviation, or median and interquartile range, as appropriate and categorical variables were summarized as percentages. Conversion of the database into an SPSS data file was performed using SPSS version 15 for windows which was the software used for conducting the statistical analysis.
Table 1. Baseline Characteristics of the Cohort. Variable Age (mean + SD) 75 years 65-74 years 64 years Sex Male Female Nationality Saudi Obesity BMI 25 kg/m2 HTN DM Dyslipidemia Prior stroke/TIA RHD CHF CAD History of smoking Premature CAD Premature Sudden death Family History of AF 12 months hospitalization HF ACS Stroke
Patients (n ¼ 400) 61.7 82 98 220
+ 15.9 (20.5) (24.5) (55)
206 (51.5) 194 (48.5) 337 (84.2) 311 253 192 173 36 115 127 114 92 25 9 24
(77.7) (63.2) (48) (44) (9) (28.7) (31.7) (28.5) (23) (6.3) (2.3) (6)
62 (15.5) 56 (14) 31 (7.7)
Abbreviations: SD, standard deviation; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; TIA, transient ischemic attack; RHD, rheumatic heart disease; CHF, congestive heart failure; CAD, coronary artery disease; AF, atrial fibrillation; HF, heart failure; ACS, acute coronary syndrome.
Results Characteristics of Patients A total of 415 patients with AF were enrolled in SAS between April 2011 and November 2011. Of these, 15 (3.6%) patients were excluded due to protocol violation due to noncompliance with inclusion/exclusion criteria. Baseline characteristics of the cohort are shown in Table 1. The mean age of the cohort was 61.7 + 15 years. The majority of the patients were male (n ¼ 206; 51.5%), and there was a high prevalence of HTN (n ¼ 253; 63.2%), DM (n ¼ 192; 43%), dyslipidemia (n ¼ 173; 44%), and overweight or obesity with a body mass index >25 (n ¼ 311; 77.7%). Smoking was present in 23% (n ¼ 92), HF in 31.7% (n ¼ 127), rheumatic heart disease in 28.7% (n ¼ 115), and coronary artery disease (CAD) in 28.5% (n ¼ 114). Of the total cohort, 149 (37.2%) patients were hospitalized in the 12 months prior to enrollment. Reasons for hospitalization included congestive heart failure in 62 (15.5%), acute coronary syndrome in 56 (14%), and stroke in 31 (7.7%) patients. Atrial fibrillation characteristics and management strategies of the cohort are shown in Tables 2 and 3. Of the total cohort, the most frequent type of AF was permanent (n ¼ 180; 45%), followed by paroxysmal (n ¼ 98; 24.5%), and persistent (n ¼ 70; 17.5%). In all, 180 (47.4%) patients were European Heart Rhythm Association (EHRA) class I, 113
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Table 2. Characteristics and Management Strategies of Atrial Fibrillation Patients. Variable Types of AF Paroxysmal Persistent Permanent New onset EHRA (data available for 325 patients) Class I Class II Class III Class IV Palpitation Dyspnea Fatigue Dizziness Rate control by ECG Yes 80 bpm Duration of AF ECHO done
Patients (n ¼ 400) 98 70 180 52
(24.5) (17.5) (45) (13)
154 113 51 7 85 82 53 35
(47.4) (34.8) (15.7) (2.1) (21.3) (20.5) (13.3) (8.8)
211 (52.7) 3 years 296 (74)
Abbreviations: AF, atrial fibrillation; EHRA, European Heart Rhythm Association; ECG, electrocardiogram; ECHO, echocardiogram.
Table 3. Management Strategies of Patients With Atrial Fibrillation. Variable Management strategy Rate control Rhythm control Unknown Both Missing data Medication b-Blocker CCB Digoxin Antiarrhythmic therapy Amiodarone Sotalol Flecainide Electrical cardioversion attempted Ablation
Patients (n ¼ 400) 265 (66.25) 48 (12) 63 (15.75) 5 (1.25) 19 (4.75) 264 (66) 83 (20.8) 121 (30.3) 170 (42.3) 140 (35) 91 (22.7) 37 (11.6) 15 (3.8)
Abbreviations: CCB, Calcium Channel Blocker.
(34.8%) were EHRA class II, 51 (15.7%) were EHRA class III, and 7 (2.1%) were EHRA class IV. Two-hundred and fifty-five (63.4%) patients reported symptoms related to AF in the last 2 weeks prior to enrollment. The most frequent symptom reported was palpitation in 85 (21.3%) patients, followed by dyspnea in 82 (20.5%), fatigue in 53 (13.3%), and dizziness in 35 (8.8%). Rate control was the most frequent management strategy in 265 (66.2%) patients whereas rhythm control was chosen in 48 (12%) patients. Both strategies were attempted in 5 (1.2%) patients. Eighty-two patients had either no data or unknown management strategy. The most frequent antiarrhythmic medication used in this cohort was amiodarone in 170 (42.5%)
80% 70% 60% 50% 40% 30% 20% 10% 0%
69.6%
68.1%
57.2% 42.8% 31.9%
30.4%
CHA2DS2-VASc Score = 0
CHA2DS2-VASc Score = 1
Acetyl salicylic acid
CHA2DS2-VASc Score ≥ 2
Vitamin K antagonists
Figure 1. Stroke risk stratification and antithrombotic use by *CHA2DS2-VASc score. * indicates congestive heart failure, age 75 years, diabetes, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex (female).
patients, followed by sotalol in 140 (25%), and flecainide in 91 (22.7%). Direct cardioversion was attempted in 37 (11.6%) patients and catheter-based AF ablation in 15 (3.8%) patients. Figure 1 depicts stroke risk stratification and antithrombotic use by CHA2DS2-VASc scores. Of the total cohort, 302 (75.5%) patients were given an antithrombotic agent for stroke prevention. The most frequent agent used was vitamin K antagonists prescribed in 154 (38.5%) patients, followed by aspirin in 142 (35.5%) patients, and 6 (1.5%) patients used other antiplatelet agents. Vitamin K antagonists were used in 4 (57.2%) of 7 patients with CHA2DS2-VASc score ¼ 0, and in 130 (68%) of the 191 patients in CHA2DS2-VASc score 2.
Discussion This study is the first prospective multicenter survey assessing the clinical characteristics, management, and outcomes of patients with AF in Saudi Arabia. Age is an important risk factor for the development of AF. In the developed countries, the mean age of patients with AF is 70 years21; in contrast, patients in other studies including ours were younger.22,23 Worldwide, the reported proportion of women with AF ranges from 35% to 56%,20 which is similar to 48% of women with AF in our patients. Additionally, the rate of HTN, congestive HF, CAD, and stroke was similar to those in other reports.20 Conversely, the rate of DM of 48% in our study is the highest reported in the literature. Atrial fibrillation was secondary to valvular heart disease in 28% of patients in our study, consistent with other reports from African and Asian countries.22,23 The proportion of different types of AF in our study was similar to other reports.24-27 The majority of our patients had EHRA class I or II. The American College of Cardiology, American Heart Association, and European Society of Cardiology guidelines advocate using rhythm control strategy in symptomatic patients with AF.28 In the Euro Heart Survey, which yielded the first regional snapshot of current AF management—analysis of 5333 ambulant and hospitalized patients with AF—the use of rhythm control strategy was 67%.29 Nevertheless, the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry enrolled more than 10 000 patients in the United States from different practice settings and found that 68% were managed with rate control versus 32% with rhythm control.30 In a multivariate
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logistic regression model, predictors of rhythm control in the ORBIT-AF registry cohort were high symptoms score and referral to an electrophysiologist.31 These findings are in line with our study where 66% of our cohort with AF were managed with rate control strategy; however, this has not been consistent across studies. Potential explanation for this variability in adherence to the guidelines includes different patient populations and settings, types of AF, and awareness of the guidelines. The overall rate of oral anticoagulation (OAC) use in our study was high (75%); this is higher than what was reported in several studies (32% to 64%).20 Furthermore, a high proportion who are ineligible for OAC received it (57%) and this rate is similar to 40% in the Euro Heart survey.29 In contrast, 31% of high-risk patients for stroke did not receive OAC. Plausible explanations for this paradox of overuse of OAC in low-risk patients and underuse in high-risk patients include a knowledge gap due to lack of awareness of the indication for OAC, lack of access to anticoagulation clinic, patient preference, and other comorbidities that put the patient at high risk of bleeding. However, many physicians have concerns about bleeding that is caused by OAC therapy that they initiated more than stroke risk. Therefore, given the significant and global burden of AF, our data and several other studies highlight the need for OAC. These data call for an immediate action to bridge this knowledge and care gap in this population. The most recent European AF guidelines has recommend CHA2DS2-VASc for the assessment of the risk of stroke combined with the validated Hypertension, Abnormal liver or renal function, Stroke, Bleeding, Labial INR, Elderly >65, Drugs score to assess the risk of bleeding.32 In addition, in the last 3 years 3 new OACs were approved by regulatory authorities with a good benefit/risk profile and no need for monitoring. Consequently, we would potentially imagine that these tools and new agents would make stroke prevention in patients with AF simpler and more achievable.
Limitations We strived to collect data on patients with AF from different geographical regions to ensure representativeness of patients with AF. Participation in the study was based on willingness to participate and this could potentially introduce a bias. However, the participating centers included teaching, nonteaching, and private hospitals. Some of the hospitals included were tertiary and secondary care centers. In any registry, there is a potential of selection bias during enrollment; however, to mitigate this risk we kept a log in each center. Also, bias includes the fact that all patients were not recruited consecutively. Each center provided a range of patients but not all who presented to them.
Conclusions In our study, patients with AF had the highest prevalence of DM in the world, and the most predominant management strategy was rate control. The survey also shows underuse of OAC in high-risk patients and overuse in low-risk patients. Better
adherence to the guidelines is needed to properly manage patients with AF in this part of the world. Acknowledgment Sanofi-Aventis financially sponsored this survey.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support from Sanofi-Aventis and the college of Medicine Research Center at King Khalid University Hospital, King Saud University.
References 1. Greenlee RT, Vidaillet H. Recent progress in the epidemiology of atrial fibrillation. Curr Opin Cardiol. 2005;20(1):7-14. 2. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994;74(3):236-241. 3. Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155(5):469-473. 4. Wattigney WA, Mensah GA, Croft JB. Increased atrial fibrillation mortality: United States, 1980-1998. Am J Epidemiol. 2002;155(9): 819-826. 5. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European society of hypertensionEuropean society of cardiology guidelines for the management of hypertension. J Hypertens. 2003;21(6):1011-1053. 6. Furberg CD, Manolio TA, Psaty BM, et al. Major electrocardiographic abnormalities in persons aged 65 years and older (the cardiovascular health study). Am J Cardiol. 1992;69(16):1329-1335. 7. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82(8A):2N-9N. 8. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications of for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA. 2001;285(18):2370-2375. 9. Ryder KM, Benjamin EJ. Epidemiology and significance of atrial fibrillation. Am J Cardiol. 1999;84(9A):131R-138R. 10. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham study. Arch Intern Med. 1987;147(9):1561-1154. 11. Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999. Circulation. 2003;108(6):711-716. 12. Levy S. Pharmacologic management of atrial fibrillation. Current therapeutic strategies. Am Heart J. 200l;141(2 suppl):S15-S21. 13. Donahue TP, Conti JB. Atrial fibrillation: rate control versus maintenance of sinus rhythm. Curr Opin Cardiol. 2001;16(1):46-53.
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14. Prasun MA, Kocheril AG. Treating atrial fibrillation: rhythm control or rate control. J Cardiovasc Nurs. 2003;18(5):369-373. 15. Boos CJ, Carlsson J, More RS. Rate or rhythm control in persistent atrial fibrillation? QJM. 2003;96(12):881-892. 16. Vidaillet H, Greenlee RT. Rate control versus rhythm control. Curr Opin Cardiol. 2005;20(1):15-20. 17. Hersi A, Wyse DG. Medical management of atrial fibrillation. Curr Cardiol Rep. 2006;8(5):323-329. 18. Fuster V, Ryden LE, Caimom DS, et al. 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: developed in collaboration with the European heart rhythm association and the heart rhythm society. Circulation. 2006;114(7):257-354. 19. Snow V, Weiss KB, Le Fevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American academy of family physicians and the American college of physicians. Ann Intern Med. 2003;139(12):1009-1017. 20. Hersi AS, Alsheikh-Ali A, Zubaid M, Al Suwaidi J. Prospective observational studies of the management and outcomes in patients with atrial fibrillation: a systematic review. J Saudi Heart Assoc. 2012;24(4):243-252. 21. Wyse DG, Waldo AL, Dimarco JP, et al. for the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-1833. 22. Ntep-Gweth M, Zimmermann M, Meiltz A, et al. Atrial fibrillation in Africa: clinical characteristics, prognosis, and adherence to guidelines in Cameroon. Europace. 2010;12(4):482-487. 23. Habibzadeh F, Yadollahie M, Roshanipoor M, Haghighi AB. Prevalence of atrial fibrillation in a primary health care centre in Fars Province, Islamic Republic of Iran. East Mediterr Health J. 2004; 10(1-2):147-151. 24. Van Gelder IC, Hagens yE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347(23):1834-1840.
25. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation- Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. Lancet. 2000;356(9244): 1789-1794. 26. Carlsson J, Miketic 5, Windeler J, et al. Randomized trial of ratecontrol versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol. 2003;41(10):1690-1696. 27. Hohnloser SH1, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(15):668-678. 28. Fuster V, Ryden LE, Cannom DS, et al. 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(7):e257-e354. 29. Nieuwlaat R, Cappucci A, Camm AJ. Atrial fibrillation management: a prospective survey in ESC member countries. The Euro heart survey on atrial fibrillation. Eur Heart J. 2005;26(22): 2422-2434. 30. Fosbol EL, Holmes DN, Piccini JP, et al. Provider specialty and atrial fibrillation treatment strategies in United States community practice: findings from the ORBIT -AF registry. J Am Heart Assoc. 2013;2(4):e000110. 31. Steinberg BA, Holmes DN, Ezekowitz MD, et al. Rate versus rhythm control for management of atrial fibrillation in clinical practice: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J 2013;165(4):622-629. 32. Camm AJ, Kirchhof P, Lip GY, et al. 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(19):2369-2429.
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Saudi Atrial Fibrillation Survey: National, Observational, Cross-sectional Survey Evaluating Atrial Fibrillation Management and the Cardiovascular Risk Profile of Patients With Atrial Fibrillation
Angiology 2015, Vol. 66(3) 244-248 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714529180 ang.sagepub.com
Ahmad Hersi, MBBS, MSc, FRCPC1, Mohammad Abdul-Moneim, MBBS2, Abdulmohsen Almous’ad, MBBS3, Faisal Al-Samadi, MBBS, FRCPC4, Ahmed AlFagih, MBBS5, and Raid Sweidan, MD6
Abstract Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The Saudi Atrial Fibrillation Survey registry was designed to provide epidemiological and clinical data on patients with AF. The registry included 400 consecutive patients who met the eligibility criteria. Control of AF at the time of the initial visit was achieved by 211 (52.75%) patients. Cardiovascular risk profile of the patients with AF was smoking 92 (23.5%), hypertension 253 (63.25%), diabetes 192 (48%), and dyslipidemia 173 (44%). Rate control was the most frequent management strategy (in 265 patients, 66.2%) whereas rhythm control was chosen in 48 (12%) patients. Both strategies were attempted in 5 (1.2%) patients. This is the first nationwide registry of patients with AF in Saudi Arabia. Compared to developed countries, our patients with AF are relatively young and have higher rates of diabetes and rheumatic heart disease. Rate control is the main strategy currently used for managing AF. Keywords Saudi Arabia, atrial fibrillation, survey
Introduction Atrial fibrillation (AF) is the most common encountered arrhythmia.1,2-4 It is quite often associated with comorbidities, particularly ischemic heart disease, valvular diseases, heart failure (HF), diabetes mellitus (DM), and hypertension (HTN).2,5-7 The prevalence of AF continues to rise as the population of the developed countries ages and is expected to show a greater rise in the coming years 3,8,9 Atrial fibrillation is an important cause of morbidity, mortality, and reduced quality of life and a principal cause of hospitalization.8,10,11 Currently, there are 2 main strategies for the management of AF: one is the restoration and maintenance of sinus rhythm (rhythm control) and the other is the control of the ventricular response (rate control). Both rhythm and rate control strategies can be achieved by nonpharmacological as well as pharmacological therapies.12-17 Several randomized clinical trials have been conducted to compare these 2 strategies, and the meta-analysis of these trials showed that rate control and anticoagulation are equivalent to rhythm control strategy. Therefore, treatment guidelines have moved toward rate control and anticoagulation, with rhythm control reserved for highly symptomatic patients.18,19 The characteristics of patients included in rate control versus rhythm control trials are often different than patients treated in
real life.20 Furthermore, data on the management of patients with AF in the Middle East are scarce. Therefore, the Saudi Atrial Fibrillation Survey (SAS) was conducted to compare patients with AF in clinical trials with patients having AF in real-world experience with respect to different management strategies.
Method Study Design The SAS is a multicenter observational cross-sectional study that recruited consecutive patients with AF in 18 centers in 1
Department of Cardiac Sciences, King Saud University, Riyadh, Saudi Arabia Sanofi, Riyadh, Saudi Arabia 3 Cardiology Department, National Guard Hospital, Riyadh, Saudi Arabia 4 Cardiology Department, Prince Salman Heart Center, Riyadh, Saudi Arabia 5 Cardiology Department, Prince Sultan Cardiac Center, Riyadh, Saudi Arabia 6 Cardiology Department, King Fahad Military Hospital, Jeddah, Saudi Arabia 2
Corresponding Author: Ahmad Hersi, Department of Cardiac Sciences, College of Medicine, King Saud University, PO Box 7805 (92), Riyadh, 11472, Saudi Arabia. Email: [email protected]
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Saudi Arabia between April 2011 and November 2011. Each site was asked to recruit a target of 20 to 30 patients. Patients included in the study were aged 18 years with a history of AF (treated or not and whatever the rhythm at inclusion) with at least 1 AF episode documented by standard electrocardiogram (ECG) or by ECG-Holter monitoring in the last 12 months or documented current AF. Patients were asked to participate and sign a written informed consent (obtained from patients or their legal representatives). Those with 1 of the following criteria were excluded from the study: mental disability (including dementia and significant cognitive disorders), unable to understand or sign the written informed consent, postcardiac surgery AF (AF within 3 months after surgery), and participated in a clinical trial in the field of AF or in the field of antithrombotic treatment in the previous month. In order to allow extrapolation of the results to the broadest possible population, patients were recruited from office or hospital-based cardiologists and internists practicing in governmental, private, secondary, and tertiary care centers. The primary objectives of the SAS were to assess the characteristics, management strategies, and outcomes of patients with AF in a real world setting in Saudi Arabia.
Data Collection Data were collected using a paper case report form (CRF) filled by the study investigators. Data collected included the following variables: patient demographics, medical history, stroke risk profile such as congestive HF, age 75, diabetes, stroke, or transient ischemic attack, vascular disease, age 65 to 74 years, sex (female; CHA2DS2-VASc risk score), type of AF (paroxysmal, persistent, permanent, and new onset), management strategy (rhythm control vs rate control), medications use including antiarrhythmic agents, echocardiogram and ECG findings, laboratory investigations, medical therapy, use of cardiac procedures and interventions, and in-hospital outcomes in the past 12 months prior to enrollment. Data entry was carried out by experienced data entry specialists using the Microsoft Access software interface. The study monitor was responsible for solving any correction queries with the survey investigator regarding key variables (by phone, fax, e-mail, or visit). On-site data quality control was performed by study monitors through reviewing the completed CRF for 15% of a random sample of study patients against patient source documents. In addition, another quality control was performed by a data entry supervisor through reviewing the electronic data of a 5% random sample of study patients against the paper CRF.
Statistical Analysis Continuous variables were summarized as mean + standard deviation, or median and interquartile range, as appropriate and categorical variables were summarized as percentages. Conversion of the database into an SPSS data file was performed using SPSS version 15 for windows which was the software used for conducting the statistical analysis.
Table 1. Baseline Characteristics of the Cohort. Variable Age (mean + SD) 75 years 65-74 years 64 years Sex Male Female Nationality Saudi Obesity BMI 25 kg/m2 HTN DM Dyslipidemia Prior stroke/TIA RHD CHF CAD History of smoking Premature CAD Premature Sudden death Family History of AF 12 months hospitalization HF ACS Stroke
Patients (n ¼ 400) 61.7 82 98 220
+ 15.9 (20.5) (24.5) (55)
206 (51.5) 194 (48.5) 337 (84.2) 311 253 192 173 36 115 127 114 92 25 9 24
(77.7) (63.2) (48) (44) (9) (28.7) (31.7) (28.5) (23) (6.3) (2.3) (6)
62 (15.5) 56 (14) 31 (7.7)
Abbreviations: SD, standard deviation; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; TIA, transient ischemic attack; RHD, rheumatic heart disease; CHF, congestive heart failure; CAD, coronary artery disease; AF, atrial fibrillation; HF, heart failure; ACS, acute coronary syndrome.
Results Characteristics of Patients A total of 415 patients with AF were enrolled in SAS between April 2011 and November 2011. Of these, 15 (3.6%) patients were excluded due to protocol violation due to noncompliance with inclusion/exclusion criteria. Baseline characteristics of the cohort are shown in Table 1. The mean age of the cohort was 61.7 + 15 years. The majority of the patients were male (n ¼ 206; 51.5%), and there was a high prevalence of HTN (n ¼ 253; 63.2%), DM (n ¼ 192; 43%), dyslipidemia (n ¼ 173; 44%), and overweight or obesity with a body mass index >25 (n ¼ 311; 77.7%). Smoking was present in 23% (n ¼ 92), HF in 31.7% (n ¼ 127), rheumatic heart disease in 28.7% (n ¼ 115), and coronary artery disease (CAD) in 28.5% (n ¼ 114). Of the total cohort, 149 (37.2%) patients were hospitalized in the 12 months prior to enrollment. Reasons for hospitalization included congestive heart failure in 62 (15.5%), acute coronary syndrome in 56 (14%), and stroke in 31 (7.7%) patients. Atrial fibrillation characteristics and management strategies of the cohort are shown in Tables 2 and 3. Of the total cohort, the most frequent type of AF was permanent (n ¼ 180; 45%), followed by paroxysmal (n ¼ 98; 24.5%), and persistent (n ¼ 70; 17.5%). In all, 180 (47.4%) patients were European Heart Rhythm Association (EHRA) class I, 113
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Table 2. Characteristics and Management Strategies of Atrial Fibrillation Patients. Variable Types of AF Paroxysmal Persistent Permanent New onset EHRA (data available for 325 patients) Class I Class II Class III Class IV Palpitation Dyspnea Fatigue Dizziness Rate control by ECG Yes 80 bpm Duration of AF ECHO done
Patients (n ¼ 400) 98 70 180 52
(24.5) (17.5) (45) (13)
154 113 51 7 85 82 53 35
(47.4) (34.8) (15.7) (2.1) (21.3) (20.5) (13.3) (8.8)
211 (52.7) 3 years 296 (74)
Abbreviations: AF, atrial fibrillation; EHRA, European Heart Rhythm Association; ECG, electrocardiogram; ECHO, echocardiogram.
Table 3. Management Strategies of Patients With Atrial Fibrillation. Variable Management strategy Rate control Rhythm control Unknown Both Missing data Medication b-Blocker CCB Digoxin Antiarrhythmic therapy Amiodarone Sotalol Flecainide Electrical cardioversion attempted Ablation
Patients (n ¼ 400) 265 (66.25) 48 (12) 63 (15.75) 5 (1.25) 19 (4.75) 264 (66) 83 (20.8) 121 (30.3) 170 (42.3) 140 (35) 91 (22.7) 37 (11.6) 15 (3.8)
Abbreviations: CCB, Calcium Channel Blocker.
(34.8%) were EHRA class II, 51 (15.7%) were EHRA class III, and 7 (2.1%) were EHRA class IV. Two-hundred and fifty-five (63.4%) patients reported symptoms related to AF in the last 2 weeks prior to enrollment. The most frequent symptom reported was palpitation in 85 (21.3%) patients, followed by dyspnea in 82 (20.5%), fatigue in 53 (13.3%), and dizziness in 35 (8.8%). Rate control was the most frequent management strategy in 265 (66.2%) patients whereas rhythm control was chosen in 48 (12%) patients. Both strategies were attempted in 5 (1.2%) patients. Eighty-two patients had either no data or unknown management strategy. The most frequent antiarrhythmic medication used in this cohort was amiodarone in 170 (42.5%)
80% 70% 60% 50% 40% 30% 20% 10% 0%
69.6%
68.1%
57.2% 42.8% 31.9%
30.4%
CHA2DS2-VASc Score = 0
CHA2DS2-VASc Score = 1
Acetyl salicylic acid
CHA2DS2-VASc Score ≥ 2
Vitamin K antagonists
Figure 1. Stroke risk stratification and antithrombotic use by *CHA2DS2-VASc score. * indicates congestive heart failure, age 75 years, diabetes, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex (female).
patients, followed by sotalol in 140 (25%), and flecainide in 91 (22.7%). Direct cardioversion was attempted in 37 (11.6%) patients and catheter-based AF ablation in 15 (3.8%) patients. Figure 1 depicts stroke risk stratification and antithrombotic use by CHA2DS2-VASc scores. Of the total cohort, 302 (75.5%) patients were given an antithrombotic agent for stroke prevention. The most frequent agent used was vitamin K antagonists prescribed in 154 (38.5%) patients, followed by aspirin in 142 (35.5%) patients, and 6 (1.5%) patients used other antiplatelet agents. Vitamin K antagonists were used in 4 (57.2%) of 7 patients with CHA2DS2-VASc score ¼ 0, and in 130 (68%) of the 191 patients in CHA2DS2-VASc score 2.
Discussion This study is the first prospective multicenter survey assessing the clinical characteristics, management, and outcomes of patients with AF in Saudi Arabia. Age is an important risk factor for the development of AF. In the developed countries, the mean age of patients with AF is 70 years21; in contrast, patients in other studies including ours were younger.22,23 Worldwide, the reported proportion of women with AF ranges from 35% to 56%,20 which is similar to 48% of women with AF in our patients. Additionally, the rate of HTN, congestive HF, CAD, and stroke was similar to those in other reports.20 Conversely, the rate of DM of 48% in our study is the highest reported in the literature. Atrial fibrillation was secondary to valvular heart disease in 28% of patients in our study, consistent with other reports from African and Asian countries.22,23 The proportion of different types of AF in our study was similar to other reports.24-27 The majority of our patients had EHRA class I or II. The American College of Cardiology, American Heart Association, and European Society of Cardiology guidelines advocate using rhythm control strategy in symptomatic patients with AF.28 In the Euro Heart Survey, which yielded the first regional snapshot of current AF management—analysis of 5333 ambulant and hospitalized patients with AF—the use of rhythm control strategy was 67%.29 Nevertheless, the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry enrolled more than 10 000 patients in the United States from different practice settings and found that 68% were managed with rate control versus 32% with rhythm control.30 In a multivariate
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logistic regression model, predictors of rhythm control in the ORBIT-AF registry cohort were high symptoms score and referral to an electrophysiologist.31 These findings are in line with our study where 66% of our cohort with AF were managed with rate control strategy; however, this has not been consistent across studies. Potential explanation for this variability in adherence to the guidelines includes different patient populations and settings, types of AF, and awareness of the guidelines. The overall rate of oral anticoagulation (OAC) use in our study was high (75%); this is higher than what was reported in several studies (32% to 64%).20 Furthermore, a high proportion who are ineligible for OAC received it (57%) and this rate is similar to 40% in the Euro Heart survey.29 In contrast, 31% of high-risk patients for stroke did not receive OAC. Plausible explanations for this paradox of overuse of OAC in low-risk patients and underuse in high-risk patients include a knowledge gap due to lack of awareness of the indication for OAC, lack of access to anticoagulation clinic, patient preference, and other comorbidities that put the patient at high risk of bleeding. However, many physicians have concerns about bleeding that is caused by OAC therapy that they initiated more than stroke risk. Therefore, given the significant and global burden of AF, our data and several other studies highlight the need for OAC. These data call for an immediate action to bridge this knowledge and care gap in this population. The most recent European AF guidelines has recommend CHA2DS2-VASc for the assessment of the risk of stroke combined with the validated Hypertension, Abnormal liver or renal function, Stroke, Bleeding, Labial INR, Elderly >65, Drugs score to assess the risk of bleeding.32 In addition, in the last 3 years 3 new OACs were approved by regulatory authorities with a good benefit/risk profile and no need for monitoring. Consequently, we would potentially imagine that these tools and new agents would make stroke prevention in patients with AF simpler and more achievable.
Limitations We strived to collect data on patients with AF from different geographical regions to ensure representativeness of patients with AF. Participation in the study was based on willingness to participate and this could potentially introduce a bias. However, the participating centers included teaching, nonteaching, and private hospitals. Some of the hospitals included were tertiary and secondary care centers. In any registry, there is a potential of selection bias during enrollment; however, to mitigate this risk we kept a log in each center. Also, bias includes the fact that all patients were not recruited consecutively. Each center provided a range of patients but not all who presented to them.
Conclusions In our study, patients with AF had the highest prevalence of DM in the world, and the most predominant management strategy was rate control. The survey also shows underuse of OAC in high-risk patients and overuse in low-risk patients. Better
adherence to the guidelines is needed to properly manage patients with AF in this part of the world. Acknowledgment Sanofi-Aventis financially sponsored this survey.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support from Sanofi-Aventis and the college of Medicine Research Center at King Khalid University Hospital, King Saud University.
References 1. Greenlee RT, Vidaillet H. Recent progress in the epidemiology of atrial fibrillation. Curr Opin Cardiol. 2005;20(1):7-14. 2. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994;74(3):236-241. 3. Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155(5):469-473. 4. Wattigney WA, Mensah GA, Croft JB. Increased atrial fibrillation mortality: United States, 1980-1998. Am J Epidemiol. 2002;155(9): 819-826. 5. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European society of hypertensionEuropean society of cardiology guidelines for the management of hypertension. J Hypertens. 2003;21(6):1011-1053. 6. Furberg CD, Manolio TA, Psaty BM, et al. Major electrocardiographic abnormalities in persons aged 65 years and older (the cardiovascular health study). Am J Cardiol. 1992;69(16):1329-1335. 7. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82(8A):2N-9N. 8. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications of for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA. 2001;285(18):2370-2375. 9. Ryder KM, Benjamin EJ. Epidemiology and significance of atrial fibrillation. Am J Cardiol. 1999;84(9A):131R-138R. 10. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham study. Arch Intern Med. 1987;147(9):1561-1154. 11. Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999. Circulation. 2003;108(6):711-716. 12. Levy S. Pharmacologic management of atrial fibrillation. Current therapeutic strategies. Am Heart J. 200l;141(2 suppl):S15-S21. 13. Donahue TP, Conti JB. Atrial fibrillation: rate control versus maintenance of sinus rhythm. Curr Opin Cardiol. 2001;16(1):46-53.
Downloaded from ang.sagepub.com at Freie Universitaet Berlin on May 10, 2015
248
Angiology 66(3)
14. Prasun MA, Kocheril AG. Treating atrial fibrillation: rhythm control or rate control. J Cardiovasc Nurs. 2003;18(5):369-373. 15. Boos CJ, Carlsson J, More RS. Rate or rhythm control in persistent atrial fibrillation? QJM. 2003;96(12):881-892. 16. Vidaillet H, Greenlee RT. Rate control versus rhythm control. Curr Opin Cardiol. 2005;20(1):15-20. 17. Hersi A, Wyse DG. Medical management of atrial fibrillation. Curr Cardiol Rep. 2006;8(5):323-329. 18. Fuster V, Ryden LE, Caimom DS, et al. 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: developed in collaboration with the European heart rhythm association and the heart rhythm society. Circulation. 2006;114(7):257-354. 19. Snow V, Weiss KB, Le Fevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American academy of family physicians and the American college of physicians. Ann Intern Med. 2003;139(12):1009-1017. 20. Hersi AS, Alsheikh-Ali A, Zubaid M, Al Suwaidi J. Prospective observational studies of the management and outcomes in patients with atrial fibrillation: a systematic review. J Saudi Heart Assoc. 2012;24(4):243-252. 21. Wyse DG, Waldo AL, Dimarco JP, et al. for the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-1833. 22. Ntep-Gweth M, Zimmermann M, Meiltz A, et al. Atrial fibrillation in Africa: clinical characteristics, prognosis, and adherence to guidelines in Cameroon. Europace. 2010;12(4):482-487. 23. Habibzadeh F, Yadollahie M, Roshanipoor M, Haghighi AB. Prevalence of atrial fibrillation in a primary health care centre in Fars Province, Islamic Republic of Iran. East Mediterr Health J. 2004; 10(1-2):147-151. 24. Van Gelder IC, Hagens yE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347(23):1834-1840.
25. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation- Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. Lancet. 2000;356(9244): 1789-1794. 26. Carlsson J, Miketic 5, Windeler J, et al. Randomized trial of ratecontrol versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol. 2003;41(10):1690-1696. 27. Hohnloser SH1, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(15):668-678. 28. Fuster V, Ryden LE, Cannom DS, et al. 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(7):e257-e354. 29. Nieuwlaat R, Cappucci A, Camm AJ. Atrial fibrillation management: a prospective survey in ESC member countries. The Euro heart survey on atrial fibrillation. Eur Heart J. 2005;26(22): 2422-2434. 30. Fosbol EL, Holmes DN, Piccini JP, et al. Provider specialty and atrial fibrillation treatment strategies in United States community practice: findings from the ORBIT -AF registry. J Am Heart Assoc. 2013;2(4):e000110. 31. Steinberg BA, Holmes DN, Ezekowitz MD, et al. Rate versus rhythm control for management of atrial fibrillation in clinical practice: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J 2013;165(4):622-629. 32. Camm AJ, Kirchhof P, Lip GY, et al. 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(19):2369-2429.
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