Atrial Fibrillation: An Observational Study with Outpatients ´ ALBINA, M.D.,* JULIAN ´ DE LUCA, M.D.,*,† DIEGO CONDE, M.D.,* GASTON and ALBERTO GINIGER, M.D.* *From the Department of Cardiology, Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina; and †Medical Staff Group, Sanofi-Aventis, Buenos Aires, Argentina Background: Atrial fibrillation (AF) is the most common sustained arrhythmia with serious clinical consequences in the absence of treatment. However, there are limited data on the treatment of these patients in Argentina. The objective was to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and to determine the incidence of clinical events after 12 months followup. Methods: The Atrial Fibrillation study in Argentina (FARAON) was an observational, descriptive, prospective, national, and multicentric study that included outpatients with AF, followed for 12 months. The study included 38 sites in Argentina. Each researcher included the first 10 patients who met the inclusion criteria of being over 21 and also being an AF carrier documented by electrocardiogram or Holter within 12 months prior to or at the time of enrollment. Results: A total of 373 patients were included, mean age 70 ± 11.5 years, 40% women; 65% had AF rhythm at the time of inclusion, 57% had permanent AF, and 56% were asymptomatic. At the time of enrollment, 40% of physicians opted for rhythm control strategy. β-blockers and amiodarone were the most used drugs. Patients with rhythm control drugs had higher success rate than those with frequency control drug therapy (80% vs 57%). Conclusion: Cardiologists in Argentina receive patients with AF that are mostly permanent AF. More than half of the patients are asymptomatic. They opt primarily by controlling the pace. When choosing antiarrhythmic drugs, nearly half of them indicated amiodarone. (PACE 2014; 37:1485–1491) atrial fibrillation, anticoagulation, rhythm control, rate control, antiarrhythmic drugs, Argentina
Introduction Atrial fibrillation (AF) is the most frequent sustained arrhythmia; prevalence ranges from 0.4% to 1% in the general population, rising up to 10% in subjects older than 80 years.1–4 At any age, incidence is 1.5 times more frequent in men than in women.4 Even though AF can be present in patients with no cardiac structural disease, there
‡ The
investigators are listed in Appendix II. Disclosure: The FARAON Registry was sponsored by SanofiAventis in Argentina. Conflicts of Interest: Dr. Gaston Albina and Dr. Diego Conde declare no conflicts of interest. Dr. Julian De Luca is a member of the Sanofi Group Staff. Dr. Alberto Giniger is a consultant/advisor for Bristol-Myers Squibb and Pfizer. Address for reprints: Diego Conde, M.D., Department of Cardiology, Instituto Cardiovascular de Buenos Aires, Blanco Encalada 1543, Buenos Aires 1428, Argentina. Fax: 54 11 4787 7500 ext 3170; e-mail: [email protected] Received March 12, 2014; revised May 27, 2014; accepted May 31, 2014.
are some independent associated factors such as age, gender, ischemic heart disease, hypertension, cardiac failure, and rheumatologic disease.4–6 AF is the most frequent arrhythmia cause of admittance to hospital.7 There are two main current approaches to AF management: cardioversion and maintenance to sinus rhythm (SR; rhythm control) and ventricular response control (rate control).8–10 In the AFFIRM trial, the largest available trial comparing both approaches, no significant differences regarding mortality could be found.11 Similar results were obtained in the RACE (RAte Control vs Electrical cardioversion for persistent atrial fibrillation) and PIAF (Pharmacological Intervention in Atrial Fibrillation).12,13 Regarding stroke prevention, a clear benefit is obtained with anticoagulation, compared to aspirin or placebo in high-risk patients. For low-risk patients, bleeding risk with anticoagulants overwhelms the benefits for stroke prevention, so aspirin or nothing is recommended.14 Information about management of AF in real life comes from clinical studies or registries performed mainly in Europe and the United States.
doi: 10.1111/pace.12462
© 2014 Wiley Periodicals, Inc. PACE, Vol. 37
November 2014
1485
ALBINA, ET AL.
There is scarce availability of local data. In our country, a multicenter study was carried out during the last decade in which various factors related to this population were evaluated. It calls to our attention that the drug agent most frequently used for the control of ventricular response was digoxin (55%).15 The goal of this registry was to obtain updated and detailed information about the management of AF in Argentina and characteristics of the population suffering from this condition, and to find out the incidence of events in this population after a 12-month follow-up. This study will be conducted in a sample of outpatients by their treating physicians. The main aims were to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and thromboembolic prophylaxis during their routine practice; to determine the incidence of clinical events after 12 ± 2 months’ follow-up in a cohort of patients with nonacute AF; to measure the rate of therapeutic success (defined as SR or cardiac rate [CR] at rest lower or equal to 80/min plus absence of clinical events) after 12 ± 2 months of follow-up of the cohort; to determine the control rate (SR or CR at rest lower or equal to 80/min) after 12 ± 2 months of follow-up; to establish the incidence of drugrelated adverse events and to identify associated factors to clinical events. Methods The study Atrial Fibrillation in Argentina: an observational study with outpatients (FARAON) was approved by all appropriate national regulatory authorities and ethics committees of the participating centers. This study was conducted in accordance with the principles laid by the 18th World Medical Assembly (Helsinki, 1964) and all subsequent amendments. Each participating site locally ensured all necessary regulatory submissions (e.g., institutional review board/independent ethics committee) were performed in accordance with local regulations, including local data protection regulations. All the authors vouch for the accuracy and completeness of the data and the analyses. It is an observational, descriptive, prospective, national, and multicenter study which comprises a cross-sectional study: to evaluate the characteristics and usual management of the nonacute AF in Argentina and a longitudinal, prospective study after 12 ± 2 months follow-up to evaluate the incidence of adverse events and therapeutic success in the cohort of patients with nonacute AF included. Researchers (from cities with a population greater than 1,200,000 inhabitants) were randomly
1486
selected from a list of cardiologists provided by prescription auditing companies. The number of researchers per city was determined on the basis of the population of each city. Each selected researcher included the first 10 consecutive patients who met all the inclusion criteria and none of the exclusion criteria, independently of the purpose of the visit. The recruitment period lasted 9 months, based upon the outpatient practice. The study was conducted from October 27, 2009 to August 12, 2011. The follow-up period lasted 12 ± 2 months. An enrollment visit (V0) and two follow-up visits at 6 months (V1) and 12 (V2) months were performed. To be eligible, patients had to be older than 21 years old; past history of: documented AF by an electrocardiogram (ECG) or 24-hour Holter ECG study result documenting the arrhythmia or study result documented in the patients’ charts, within 12 months prior to the inclusion visit (V0). Hospitalized patients, pregnant women, history of cardiac surgery within the previous 3 months, patients in plan of radiofrequency ablation, or pacemaker or cardioverter device implant were excluded. To see the complete inclusion/exclusion criteria refer to Appendix I. All patients were provided written Informed Consent. Social demographic characteristics, cardiovascular risk factors and past history, thromboembolic past history, and any other cardiac comorbidity data were collected. The main evaluation criteria of this study were the rate of therapeutic success (defined as SR or CR at rest lower or equal to 80/min plus absence of clinical events) after 12 ± 2 months of follow-up of the cohort, the control rate (SR or CR at rest lower or equal to 80/min) after 12 ± 2 months of follow-up, and the incidence of clinical events after 12 ± 2 months followup. Any of the following are defined as clinical events: death due to cardiovascular causes (CV); hemorrhagic, ischemic, or unknown cause of stroke; transient ischemic attack (TIA) resulting in hospitalization; peripheral vascular disease; hospitalization due to arrhythmia or proarrythmic events; hospitalization due to other cardiovascular disease; and hospitalization or prolonged stay in hospital resulting from complications in the ablation procedure. Categorical variables were described by frequencies and proportions. For quantitative variables, numerical summary measures were used: mean, median, as well as measures of dispersion: interquartile range and standard deviation (SD). T-test was used to compare two sets (continuous data with normal distribution). Wilcoxon
November 2014
PACE, Vol. 37
ATRIAL FIBRILLATION IN OUTPATIENTS
rank-sum test was used for continuous data not normally distributed, and the χ 2 or Fischer’s test (for categorical data). To test association among different variables and the occurrence of events, bi- and multivariate models were used. Odds ratio (OR) was used as the association measure. In all cases, a level of significance (P) of 0.05 was established. Logistic regression model: Dependent variable: patient with at least one “clinical event” during the 12 ± 2 months follow-up. The independent variables selected were: socialdemographic characteristics, cardiovascular risk factors, cardiovascular disease, and prescribed treatment. Variables were removed stepwise from the model when the P value exceeded 0.15. Variables with P value 70 years w/RF (n = 39) >75 years/with or without RF (n = 129)
P: 0.000 OR: 0.32 95% CI: 0.18–0.55 Statistical Significance P: 0.000 OR: 0.19 95% CI: 0.09–0.37
= risk factor. AF = atrial fibrillation; CI = confidence interval; OR = odds ratio.
a RF
the calibration and discrimination capacity were low. Discussion AF is the most common cardiac sustained arrhythmia. Although there has been important progress in treatment, AF remains an independent predictor of morbidity and mortality.1 The FARAON trial is the first epidemiologic study performed after a decade in Argentina. There were 373 subjects included. The average age was 70 years in concordance with the results shown in the majority of trials about prevalence worldwide.16 Sex was mainly male as also reported by Ryder and Benjamin in an epidemiologic review conducted in the United States.17 Nearly two-thirds of the population lived in Buenos Aires city and its suburbs. Half of the population completed university or high school. Ninety percent had some kind of health coverage. At enrollment, more than half of the subjects had permanent AF, with it being the first event in 3% of the cases. Half of them were taking β-blockers (in contrast with the digoxin strategy used in the past)15 ; 41% received amiodarone and 19%, digoxin. Regarding anticoagulation, 68% were on acenocoumarol and 39%, aspirin at enrollment. After 1-year follow-up, AF treatment strategy remained very much the same but the anticoagu-
PACE, Vol. 37
lation medication treatment dropped to 57%, and use of aspirin decreased to 31.6%. The most frequent comorbidities in this population were hypertension, diabetes, heart failure, and past medical history of stroke/TIA. Hypertension was responsible for more AF than any other risk factor due to its high prevalence in the population, higher than reported in other trials.6,15 Argentine cardiologists know both AF treatments, and their first choice is the rate control strategy. Once a therapy strategy is chosen, there is very little crossover. In 93.2% of the cases, anticoagulation is handled by hematologists. The rate of adverse events occurred mostly when the rhythm control strategy was chosen, as well as in other series presented.12,13 The most frequent adverse events found were general symptoms such as syncope, fatigue, lethargy, and others. It should also be highlighted that 15% of participants presented thyroid dysfunction, due to the use of amiodarone. As in other series reported, less than half of the patients who received amiodarone were tested for thyroid dysfunction, although this is a recommended practice.14 In the sample assessed, twenty-nine patients had anticoagulation contraindications. It is important to point out that the most frequent causes were social limitation and the patient’s own decision to
November 2014
1489
ALBINA, ET AL.
discontinue the treatment. A patient’s adherence and acceptance is one of the major challenges in thromboembolic therapy, and it shows how much influence social and cultural variables have when implementing this strategy.15 There are different trials showing the costbenefit of treatment with anticoagulants in patients over 75 years old although this is a population with greater predisposition to adverse events and poor understanding of the care needed.4,15 These results demonstrate that in spite of social limitations, it is possible to carry out effective and safe anticoagulation treatments in high-risk populations, and it calls the attention against prejudice for not prescribing anticoagulation treatment to elderly patients. The rates of AF control and therapeutic success were 80% and 74%, respectively—a ratio significantly higher than the results obtained by other local studies.15 In the RACE study, it was observed that the rate control strategy showed no inferiority than the rhythm control strategy in the prevention of cardiovascular morbidity and mortality. In this trial, it was found that stroke incidence and death rate were similar to other trials. However, hospitalizations due to arrhythmia, proarrhythmic events, and other cardiovascular events showed higher figures than other clinical studies.11,12 The incidence of clinical events, stroke, or hospitalization showed no association with the antiarrhythmic therapy chosen, in concordance with the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, which also showed no difference on mortality or stroke ratios associated with the selection of the treatment strategy.11–13
Limitations Some of the potential limitations of this study were the sample, which did not respond to a probabilistic population sampling. It is also important to highlight that the sample did not include all the social classes and all the geographic regions or educational levels, and the prepaid health coverage was overestimated. On the other hand, the loss of follow-up was higher than 20%, which would make the findings biased. Some comorbidity may befall during longterm follow-up. Given that this study lasted 12 months, they may be underestimated in this trial. Given that hospitalized patients and those with history of cardiac surgery within the previous 3 months were excluded, high-risk patients were not considered. This arrhythmia is extremely frequent, particularly in the elderly population and in patients with organic heart disease. Coordinated efforts will be needed to achieve the increasing challenge of AF management. Conclusions In this cohort, the most frequent type of AF was the permanent one. The antiarrhythmic strategy mostly used was the rate control, and nearly half of the patients were on antithrombotic drugs. Two-thirds of the population included achieved therapeutic success and AF control; this outcome was higher in the rhythm control group, with statistical significance. However, results indicate that neither of the two therapeutic strategies is superior in terms of AF clinical events. Ten percent of the population had an adverse event related to antiarrhythmic medication, being higher the incidence in those patients treated with rhythm control strategy.
References 1. Greenlee RT, Vidaillet H. Recent progress in the epidemiology of atrial fibrillation. Curr Opin Cardiol 2005; 20:7–14. 2. Wattigney WA, Mensah GA, Croft JB. Increased atrial fibrillation mortality: United States 1980–1998. Am J Epidemiol 2002; 155:819– 826. 3. Fuster V, Ryd´en LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA,Halperin JL, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation. Circulation 2006; 114:e257–e354. 4. 2003 European Society of Hypertension: European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21:1011–1053. 5. Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994; 74:236– 241. 6. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: Population based estimates. Am J Cardiol 1998; 82:2N–9N. 7. Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999. Circulation 2003; 108:711–716.
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8. Levy S. Pharmacologic management of atrial fibrillation. Current therapeutic strategies. Am Heart J 2001; 141:S15–S21. 9. Donahue TP, Conti JB. Atrial fibrillation: Rate control versus maintenance of sinus rhythm. Curr Opin Cardiol 2001; 16:46–53. 10. Boos CJ, Carlsson J, More RS. Rate or rhythm control in persistent atrial fibrillation? QJM 2003; 96:881–892. 11. Wyse DG, Waldo AL, Dimarco JP, Domanski MJ, Rosemberg Y, Schron EB, Kellen JC, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825–1833. 12. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347:1834–1840. 13. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): A randomized trial. Lancet 2000; 9244:1789–1794. 14. Nieuwlaat R, Cappucci A, Camm AJ, Olsson SB, Andresen D, Davies DW, Cobbe S, et al, on behalf of the Euro Heart Survey Investigators. Atrial fibrillation management: A prospective survey in ESC member countries. The Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2005; 26:2422–2434.
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ATRIAL FIBRILLATION IN OUTPATIENTS 15. Labadet C, Liniado G, Ferreiros ´ ER, Molina Viamonte V, Di Toro D, Cragnolino R, Sansalone R, et al. Resultados del Primer Estudio Nacional, multic´entrico y prospectivo de fibrilacion ´ auricular cronica en la Republica Argentina. Rev Argent Cardiol. 2001; 69:49– ´ ´ 67. 16. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. 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. J Am Med Assoc 2001; 285:2370–2375. 17. Ryder KM, Benjamin EJ. Epidemiology and significance of atrial fibrillation. Am J Cardiol 1999; 84:131R–138R.
Appendix: Inclusion/Exclusion Criteria I Inclusion Criteria: 1. Men or women older than 21 years old. 2. Past history of: r Documented atrial fibrillation by an ECG or 24-hour Holter ECG study result documenting the arrhythmia or study result documented in the patients’ charts, within 12 months prior to the inclusion visit (V0) (treated or not at the moment of inclusion due to any rhythm at the inclusion visit). r Or having atrial fibrillation diagnosed during the inclusion visit (diagnosed by an ECG or 24-hour Holter ECG). 3. Outpatient setting. 4. Patient willing to sign the Informed Consent Form. Exclusion Criteria: 1. Transient atrial fibrillation due to thyrotoxicosis. 2. Alcoholic intoxication. 3. Acute phase of myocardial infarction. 4. Myocarditis, pericarditis. 5. Hypokalemia, anemia, electrocution.
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6. AF requiring hospitalization. 7. Patient with past history of atrial flutter only. 8. AF after cardiac surgery (within 3 months postsurgery). 9. Life expectancy less than 1 year (according to investigator’s opinion) due to a severe disease. 10. Mentally impaired subjects who are unable to understand and sign the Informed Consent Form (ICF). 11. Patients unable to comply with the follow-up visits. 12. Patients with a pacemaker or implantable heart cardioverter/defibrillator device. 13. Patients in plan of radiofrequency ablation or pacemaker or cardioverter device implanting. 14. Patients who might change their treating physician during the next year. 15. Pregnant or breastfeeding women. 16. Hospitalized patients; patient who refused to sign the ICF. Appendix II The following persons participated in the FARAON Registry: Dr. E. Rusak, Dr. O. Montana, ˜ Dr. S. Dubner, Dr. C. Millitello, Dr. R. Iglesias, Dr. G. Maid, Dr. J. Aiub, Dr. J.C. Medrano, Dr. C. Labadet, Dr. A. Sinisi, Dr. V. Mezzalira, Dr. S. Chehkerdemian, Dr. J.L. Presta, Dr. R. Goicochea, Dr. J. Buscema, Dr. C. Cazenabe, Dr. H. Casab´e, Dr. J. Gagliardi, Dr. R. Esper, Dr. G. Mazzola, Dr. C. De Zuloaga, Dr. H. Paves Palacio, Dr. R. Lopez Santi, Dr. M. Rodriguez, Dr. A. Caccavo, Dr. F. Ferre Pacora, Dr. H. Colombo, Dr. R. Martellotto, Dr. F. Femenia, Dr. J. Piasentin, Dr. M. Hominal, Dr. R. Coloccini, Dr. J. Garguichevich, Dr. J.L. Ramos, Dr. O. Pellizon, Dr. E. Aguinaga, Dr. S. Gonzalez.
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This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
Introduction Atrial fibrillation (AF) is the most frequent sustained arrhythmia; prevalence ranges from 0.4% to 1% in the general population, rising up to 10% in subjects older than 80 years.1–4 At any age, incidence is 1.5 times more frequent in men than in women.4 Even though AF can be present in patients with no cardiac structural disease, there
‡ The
investigators are listed in Appendix II. Disclosure: The FARAON Registry was sponsored by SanofiAventis in Argentina. Conflicts of Interest: Dr. Gaston Albina and Dr. Diego Conde declare no conflicts of interest. Dr. Julian De Luca is a member of the Sanofi Group Staff. Dr. Alberto Giniger is a consultant/advisor for Bristol-Myers Squibb and Pfizer. Address for reprints: Diego Conde, M.D., Department of Cardiology, Instituto Cardiovascular de Buenos Aires, Blanco Encalada 1543, Buenos Aires 1428, Argentina. Fax: 54 11 4787 7500 ext 3170; e-mail: [email protected] Received March 12, 2014; revised May 27, 2014; accepted May 31, 2014.
are some independent associated factors such as age, gender, ischemic heart disease, hypertension, cardiac failure, and rheumatologic disease.4–6 AF is the most frequent arrhythmia cause of admittance to hospital.7 There are two main current approaches to AF management: cardioversion and maintenance to sinus rhythm (SR; rhythm control) and ventricular response control (rate control).8–10 In the AFFIRM trial, the largest available trial comparing both approaches, no significant differences regarding mortality could be found.11 Similar results were obtained in the RACE (RAte Control vs Electrical cardioversion for persistent atrial fibrillation) and PIAF (Pharmacological Intervention in Atrial Fibrillation).12,13 Regarding stroke prevention, a clear benefit is obtained with anticoagulation, compared to aspirin or placebo in high-risk patients. For low-risk patients, bleeding risk with anticoagulants overwhelms the benefits for stroke prevention, so aspirin or nothing is recommended.14 Information about management of AF in real life comes from clinical studies or registries performed mainly in Europe and the United States.
doi: 10.1111/pace.12462
© 2014 Wiley Periodicals, Inc. PACE, Vol. 37
November 2014
1485
ALBINA, ET AL.
There is scarce availability of local data. In our country, a multicenter study was carried out during the last decade in which various factors related to this population were evaluated. It calls to our attention that the drug agent most frequently used for the control of ventricular response was digoxin (55%).15 The goal of this registry was to obtain updated and detailed information about the management of AF in Argentina and characteristics of the population suffering from this condition, and to find out the incidence of events in this population after a 12-month follow-up. This study will be conducted in a sample of outpatients by their treating physicians. The main aims were to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and thromboembolic prophylaxis during their routine practice; to determine the incidence of clinical events after 12 ± 2 months’ follow-up in a cohort of patients with nonacute AF; to measure the rate of therapeutic success (defined as SR or cardiac rate [CR] at rest lower or equal to 80/min plus absence of clinical events) after 12 ± 2 months of follow-up of the cohort; to determine the control rate (SR or CR at rest lower or equal to 80/min) after 12 ± 2 months of follow-up; to establish the incidence of drugrelated adverse events and to identify associated factors to clinical events. Methods The study Atrial Fibrillation in Argentina: an observational study with outpatients (FARAON) was approved by all appropriate national regulatory authorities and ethics committees of the participating centers. This study was conducted in accordance with the principles laid by the 18th World Medical Assembly (Helsinki, 1964) and all subsequent amendments. Each participating site locally ensured all necessary regulatory submissions (e.g., institutional review board/independent ethics committee) were performed in accordance with local regulations, including local data protection regulations. All the authors vouch for the accuracy and completeness of the data and the analyses. It is an observational, descriptive, prospective, national, and multicenter study which comprises a cross-sectional study: to evaluate the characteristics and usual management of the nonacute AF in Argentina and a longitudinal, prospective study after 12 ± 2 months follow-up to evaluate the incidence of adverse events and therapeutic success in the cohort of patients with nonacute AF included. Researchers (from cities with a population greater than 1,200,000 inhabitants) were randomly
1486
selected from a list of cardiologists provided by prescription auditing companies. The number of researchers per city was determined on the basis of the population of each city. Each selected researcher included the first 10 consecutive patients who met all the inclusion criteria and none of the exclusion criteria, independently of the purpose of the visit. The recruitment period lasted 9 months, based upon the outpatient practice. The study was conducted from October 27, 2009 to August 12, 2011. The follow-up period lasted 12 ± 2 months. An enrollment visit (V0) and two follow-up visits at 6 months (V1) and 12 (V2) months were performed. To be eligible, patients had to be older than 21 years old; past history of: documented AF by an electrocardiogram (ECG) or 24-hour Holter ECG study result documenting the arrhythmia or study result documented in the patients’ charts, within 12 months prior to the inclusion visit (V0). Hospitalized patients, pregnant women, history of cardiac surgery within the previous 3 months, patients in plan of radiofrequency ablation, or pacemaker or cardioverter device implant were excluded. To see the complete inclusion/exclusion criteria refer to Appendix I. All patients were provided written Informed Consent. Social demographic characteristics, cardiovascular risk factors and past history, thromboembolic past history, and any other cardiac comorbidity data were collected. The main evaluation criteria of this study were the rate of therapeutic success (defined as SR or CR at rest lower or equal to 80/min plus absence of clinical events) after 12 ± 2 months of follow-up of the cohort, the control rate (SR or CR at rest lower or equal to 80/min) after 12 ± 2 months of follow-up, and the incidence of clinical events after 12 ± 2 months followup. Any of the following are defined as clinical events: death due to cardiovascular causes (CV); hemorrhagic, ischemic, or unknown cause of stroke; transient ischemic attack (TIA) resulting in hospitalization; peripheral vascular disease; hospitalization due to arrhythmia or proarrythmic events; hospitalization due to other cardiovascular disease; and hospitalization or prolonged stay in hospital resulting from complications in the ablation procedure. Categorical variables were described by frequencies and proportions. For quantitative variables, numerical summary measures were used: mean, median, as well as measures of dispersion: interquartile range and standard deviation (SD). T-test was used to compare two sets (continuous data with normal distribution). Wilcoxon
November 2014
PACE, Vol. 37
ATRIAL FIBRILLATION IN OUTPATIENTS
rank-sum test was used for continuous data not normally distributed, and the χ 2 or Fischer’s test (for categorical data). To test association among different variables and the occurrence of events, bi- and multivariate models were used. Odds ratio (OR) was used as the association measure. In all cases, a level of significance (P) of 0.05 was established. Logistic regression model: Dependent variable: patient with at least one “clinical event” during the 12 ± 2 months follow-up. The independent variables selected were: socialdemographic characteristics, cardiovascular risk factors, cardiovascular disease, and prescribed treatment. Variables were removed stepwise from the model when the P value exceeded 0.15. Variables with P value 70 years w/RF (n = 39) >75 years/with or without RF (n = 129)
P: 0.000 OR: 0.32 95% CI: 0.18–0.55 Statistical Significance P: 0.000 OR: 0.19 95% CI: 0.09–0.37
= risk factor. AF = atrial fibrillation; CI = confidence interval; OR = odds ratio.
a RF
the calibration and discrimination capacity were low. Discussion AF is the most common cardiac sustained arrhythmia. Although there has been important progress in treatment, AF remains an independent predictor of morbidity and mortality.1 The FARAON trial is the first epidemiologic study performed after a decade in Argentina. There were 373 subjects included. The average age was 70 years in concordance with the results shown in the majority of trials about prevalence worldwide.16 Sex was mainly male as also reported by Ryder and Benjamin in an epidemiologic review conducted in the United States.17 Nearly two-thirds of the population lived in Buenos Aires city and its suburbs. Half of the population completed university or high school. Ninety percent had some kind of health coverage. At enrollment, more than half of the subjects had permanent AF, with it being the first event in 3% of the cases. Half of them were taking β-blockers (in contrast with the digoxin strategy used in the past)15 ; 41% received amiodarone and 19%, digoxin. Regarding anticoagulation, 68% were on acenocoumarol and 39%, aspirin at enrollment. After 1-year follow-up, AF treatment strategy remained very much the same but the anticoagu-
PACE, Vol. 37
lation medication treatment dropped to 57%, and use of aspirin decreased to 31.6%. The most frequent comorbidities in this population were hypertension, diabetes, heart failure, and past medical history of stroke/TIA. Hypertension was responsible for more AF than any other risk factor due to its high prevalence in the population, higher than reported in other trials.6,15 Argentine cardiologists know both AF treatments, and their first choice is the rate control strategy. Once a therapy strategy is chosen, there is very little crossover. In 93.2% of the cases, anticoagulation is handled by hematologists. The rate of adverse events occurred mostly when the rhythm control strategy was chosen, as well as in other series presented.12,13 The most frequent adverse events found were general symptoms such as syncope, fatigue, lethargy, and others. It should also be highlighted that 15% of participants presented thyroid dysfunction, due to the use of amiodarone. As in other series reported, less than half of the patients who received amiodarone were tested for thyroid dysfunction, although this is a recommended practice.14 In the sample assessed, twenty-nine patients had anticoagulation contraindications. It is important to point out that the most frequent causes were social limitation and the patient’s own decision to
November 2014
1489
ALBINA, ET AL.
discontinue the treatment. A patient’s adherence and acceptance is one of the major challenges in thromboembolic therapy, and it shows how much influence social and cultural variables have when implementing this strategy.15 There are different trials showing the costbenefit of treatment with anticoagulants in patients over 75 years old although this is a population with greater predisposition to adverse events and poor understanding of the care needed.4,15 These results demonstrate that in spite of social limitations, it is possible to carry out effective and safe anticoagulation treatments in high-risk populations, and it calls the attention against prejudice for not prescribing anticoagulation treatment to elderly patients. The rates of AF control and therapeutic success were 80% and 74%, respectively—a ratio significantly higher than the results obtained by other local studies.15 In the RACE study, it was observed that the rate control strategy showed no inferiority than the rhythm control strategy in the prevention of cardiovascular morbidity and mortality. In this trial, it was found that stroke incidence and death rate were similar to other trials. However, hospitalizations due to arrhythmia, proarrhythmic events, and other cardiovascular events showed higher figures than other clinical studies.11,12 The incidence of clinical events, stroke, or hospitalization showed no association with the antiarrhythmic therapy chosen, in concordance with the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, which also showed no difference on mortality or stroke ratios associated with the selection of the treatment strategy.11–13
Limitations Some of the potential limitations of this study were the sample, which did not respond to a probabilistic population sampling. It is also important to highlight that the sample did not include all the social classes and all the geographic regions or educational levels, and the prepaid health coverage was overestimated. On the other hand, the loss of follow-up was higher than 20%, which would make the findings biased. Some comorbidity may befall during longterm follow-up. Given that this study lasted 12 months, they may be underestimated in this trial. Given that hospitalized patients and those with history of cardiac surgery within the previous 3 months were excluded, high-risk patients were not considered. This arrhythmia is extremely frequent, particularly in the elderly population and in patients with organic heart disease. Coordinated efforts will be needed to achieve the increasing challenge of AF management. Conclusions In this cohort, the most frequent type of AF was the permanent one. The antiarrhythmic strategy mostly used was the rate control, and nearly half of the patients were on antithrombotic drugs. Two-thirds of the population included achieved therapeutic success and AF control; this outcome was higher in the rhythm control group, with statistical significance. However, results indicate that neither of the two therapeutic strategies is superior in terms of AF clinical events. Ten percent of the population had an adverse event related to antiarrhythmic medication, being higher the incidence in those patients treated with rhythm control strategy.
References 1. Greenlee RT, Vidaillet H. Recent progress in the epidemiology of atrial fibrillation. Curr Opin Cardiol 2005; 20:7–14. 2. Wattigney WA, Mensah GA, Croft JB. Increased atrial fibrillation mortality: United States 1980–1998. Am J Epidemiol 2002; 155:819– 826. 3. Fuster V, Ryd´en LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA,Halperin JL, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation. Circulation 2006; 114:e257–e354. 4. 2003 European Society of Hypertension: European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21:1011–1053. 5. Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994; 74:236– 241. 6. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: Population based estimates. Am J Cardiol 1998; 82:2N–9N. 7. Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999. Circulation 2003; 108:711–716.
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8. Levy S. Pharmacologic management of atrial fibrillation. Current therapeutic strategies. Am Heart J 2001; 141:S15–S21. 9. Donahue TP, Conti JB. Atrial fibrillation: Rate control versus maintenance of sinus rhythm. Curr Opin Cardiol 2001; 16:46–53. 10. Boos CJ, Carlsson J, More RS. Rate or rhythm control in persistent atrial fibrillation? QJM 2003; 96:881–892. 11. Wyse DG, Waldo AL, Dimarco JP, Domanski MJ, Rosemberg Y, Schron EB, Kellen JC, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825–1833. 12. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347:1834–1840. 13. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): A randomized trial. Lancet 2000; 9244:1789–1794. 14. Nieuwlaat R, Cappucci A, Camm AJ, Olsson SB, Andresen D, Davies DW, Cobbe S, et al, on behalf of the Euro Heart Survey Investigators. Atrial fibrillation management: A prospective survey in ESC member countries. The Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2005; 26:2422–2434.
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ATRIAL FIBRILLATION IN OUTPATIENTS 15. Labadet C, Liniado G, Ferreiros ´ ER, Molina Viamonte V, Di Toro D, Cragnolino R, Sansalone R, et al. Resultados del Primer Estudio Nacional, multic´entrico y prospectivo de fibrilacion ´ auricular cronica en la Republica Argentina. Rev Argent Cardiol. 2001; 69:49– ´ ´ 67. 16. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. 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. J Am Med Assoc 2001; 285:2370–2375. 17. Ryder KM, Benjamin EJ. Epidemiology and significance of atrial fibrillation. Am J Cardiol 1999; 84:131R–138R.
Appendix: Inclusion/Exclusion Criteria I Inclusion Criteria: 1. Men or women older than 21 years old. 2. Past history of: r Documented atrial fibrillation by an ECG or 24-hour Holter ECG study result documenting the arrhythmia or study result documented in the patients’ charts, within 12 months prior to the inclusion visit (V0) (treated or not at the moment of inclusion due to any rhythm at the inclusion visit). r Or having atrial fibrillation diagnosed during the inclusion visit (diagnosed by an ECG or 24-hour Holter ECG). 3. Outpatient setting. 4. Patient willing to sign the Informed Consent Form. Exclusion Criteria: 1. Transient atrial fibrillation due to thyrotoxicosis. 2. Alcoholic intoxication. 3. Acute phase of myocardial infarction. 4. Myocarditis, pericarditis. 5. Hypokalemia, anemia, electrocution.
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6. AF requiring hospitalization. 7. Patient with past history of atrial flutter only. 8. AF after cardiac surgery (within 3 months postsurgery). 9. Life expectancy less than 1 year (according to investigator’s opinion) due to a severe disease. 10. Mentally impaired subjects who are unable to understand and sign the Informed Consent Form (ICF). 11. Patients unable to comply with the follow-up visits. 12. Patients with a pacemaker or implantable heart cardioverter/defibrillator device. 13. Patients in plan of radiofrequency ablation or pacemaker or cardioverter device implanting. 14. Patients who might change their treating physician during the next year. 15. Pregnant or breastfeeding women. 16. Hospitalized patients; patient who refused to sign the ICF. Appendix II The following persons participated in the FARAON Registry: Dr. E. Rusak, Dr. O. Montana, ˜ Dr. S. Dubner, Dr. C. Millitello, Dr. R. Iglesias, Dr. G. Maid, Dr. J. Aiub, Dr. J.C. Medrano, Dr. C. Labadet, Dr. A. Sinisi, Dr. V. Mezzalira, Dr. S. Chehkerdemian, Dr. J.L. Presta, Dr. R. Goicochea, Dr. J. Buscema, Dr. C. Cazenabe, Dr. H. Casab´e, Dr. J. Gagliardi, Dr. R. Esper, Dr. G. Mazzola, Dr. C. De Zuloaga, Dr. H. Paves Palacio, Dr. R. Lopez Santi, Dr. M. Rodriguez, Dr. A. Caccavo, Dr. F. Ferre Pacora, Dr. H. Colombo, Dr. R. Martellotto, Dr. F. Femenia, Dr. J. Piasentin, Dr. M. Hominal, Dr. R. Coloccini, Dr. J. Garguichevich, Dr. J.L. Ramos, Dr. O. Pellizon, Dr. E. Aguinaga, Dr. S. Gonzalez.
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