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CLINICAL RESEARCH: CARDIAC RHYTHM DISORDER

Monitored Atrial Fibrillation Duration Predicts Arterial Embolic Events in Patients Suffering From Bradycardia and Atrial Fibrillation Implanted With Antitachycardia Pacemakers

Alessandro Capucci, MD^_*,_*, Massimo Santini, MD, Luigi Padeletti, MD, Michele Gulizia, MD, GianLuca Botto, MD^||, Giuseppe Boriani, MD^¶, Renato Ricci, MD, Stefano Favale, MD^#, Francesco Zolezzi, MD^_**, Natale Di Belardino, MD, Giulio Molon, MD, Fabrizio Drago, MD, Giovanni Q. Villani, MD^_*, Elena Mazzini, MS^||||, Marco Vimercati, MS^||||, Andrea Grammatico, PhD^|||| on behalf of the Italian AT500 Registry Investigators

^_* Cardiology Department, Civile Hospital, Piacenza, Italy
Cardiology Department, S. Filippo Neri Hospital, Rome, Italy
Cardiology Department, Clinica Medica, University of Florence, Florence, Italy
Cardiology Department, San Luigi-S. Currò Hospital, Catania, Italy
^|| Cardiology Department, S. Anna Hospital, Como, Italy
^¶ Institute of Cardiology, University of Bologna, Bologna, Italy
^# Cardiology Department, Policlinico Hospital, Bari, Italy
^_** Cardiology Department, Civile Hospital, Vigevano, Italy
Cardiology Department, Civile Hospital, Velletri, Italy
Cardiology Department, S. Cuore Hospital, Negrar, Italy
Cardiology Department, Bambino Gesù Hospital, Rome, Italy
^|||| Clinical Department, Medtronic Italy, Milan, Italy

Manuscript received April 29, 2005; revised manuscript received June 28, 2005, accepted July 4, 2005.

^_* Reprint requests and correspondence: Dr. Alessandro Capucci, Institute of Cardiology, Civile Hospital, Divisione di Cardiologia, Ospedale "Guglielmo da Saliceto," Via Taverna 49, 29100 Piacenza, Italy (Email: progettovita{at}hotmail.com).

	Abstract

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OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies.

BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE.

METHODS: A total of 725 patients (360 men, age 71 ± 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents.

RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients’ characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up.

CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Abbreviations and Acronyms   AF = atrial fibrillation   CI = confidence interval   CTOPP = Canadian Trial Of Physiologic Pacing   IQR = interquartile range   MOST = Mode Selection Trial   OR = odds ratio   TIA = transient ischemic attack

The Mode Selection Trial (MOST) atrial diagnostics ancillary study (16) recently showed that atrial high rate episodes detected by an implanted pacemaker in sinus node disease patients are associated with a two-fold increase in the risk of death or stroke. Thus, early identification of patients with AF recurrences may have clinical importance.

The aim of this prospective multicenter observational study was to assess the incidence of arterial embolic events in patients suffering from bradycardia and symptomatic paroxysmal or persistent AF and therefore implanted with pacemakers able to deliver antitachycardia therapies. We also aimed to find predictors of arterial embolic events and to evaluate the clinical significance of AF as detected by pacemaker diagnostics.

	Methods

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Patients suffering from bradycardia, having at least a class I or II American College of Cardiology/American Heart Association indication for dual-chamber pacing (17) and a history of symptomatic atrial tachyarrhythmias (at least three symptomatic episodes within the last year before implant, one episode in the last month before implant, and electrocardiogram or 24-h Holter monitoring documentation of at least one of these episodes) were eligible for study participation.

Antithrombotic therapy.   The choice of drug treatment to prevent embolism was performed by each attending physician, who decided according to the patient’s clinical condition and his own experience and preferences.

Device characteristics and programming.   The Medtronic AT500 (Medtronic Inc., Minneapolis, Minnesota) is a dual-chamber rate-responsive pacemaker, with advanced algorithms designed for rhythm discrimination and prevention and treatment of atrial arrhythmias, as previously described (18,19). Programming of conventional pacemaker parameters were left to physician discretion. Paced and sensed atrioventricular delays were programmed with the aim of promoting intrinsic atrioventricular conduction as much as possible.

Detection of atrial arrhythmias.   The implanted devices continuously classify the rhythm status of each patient: it bases the classification on the PR Logic (Medtronic Inc.) algorithm (20,21), which has been previously tested on this device and showed 100% sensitivity, 97% specificity (18), and 100% positive predictive value (95% confidence interval [CI] in the range 96% to 100%) (21) for atrial tachyarrhythmia detection.

Data analysis.   Data about arterial embolic events were obtained at follow-up visits and, when necessary, by a telephone contact. An outcome committee of two physicians evaluated arterial embolic events, defined as the occurrence of ischemic stroke, transient ischemic attack (TIA), or peripheral arterial embolism. Ischemic stroke was defined as a neurological deficit with sudden onset, persisting for more than 24 h.

We considered as risk factors for embolic events: prior ischemic stroke or TIA, age >75 years, ejection fraction <35%, left atrium diameter >50 mm, ischemic heart disease, hypertension, heart failure, and diabetes. Patients were stratified according to the number of such risk factors at enrollment.

The possible association between AF occurrence and embolic events was studied by stratifying patients according to their device-calculated duration of AF recurrences observed at follow-up. Prespecified AF duration were at least 5 min of AF (recognized as an appropriate cutoff to select AF episodes and discard premature atrial contraction runs or spurious events [22]), and 1 day duration (which is the new measurement used in device diagnostics that daily collects long-term information about AF), during the whole observational period. An episode review committee of three physicians evaluated atrial electrograms of AF episodes saved in device diagnostics to verify detection appropriateness.

Statistical analysis.   Descriptive statistics were calculated using mean and standard deviation for normally distributed continuous variables, or median with 25th to 75th interquartile range (IQR) in case of skewed distributions. Skewness and kurtosis values were calculated, in order to document a normal distribution of each studied parameter. Absolute and relative frequencies were calculated for categorical variables.

Logistic models were fitted to evaluate patients’ clinical characteristics associated with embolic events. Odds ratios (OR) and their 95% CIs were computed. Odds ratio expresses the increased (OR >1) or decreased (OR <1) embolism risk, according to the examined characteristic. Variables that showed a p < 0.2 when compared for homogeneity between groups of patients with and without embolic events were included in the univariate analysis. After checking for collinearity, variables that showed a significant (p < 0.05) correlation with embolic events at univariate analysis were considered in the multivariate logistic models.

Cox proportional hazards models were used to examine the association between occurrence of AF episodes, longer than 5 min and longer than 1 day, and the occurrence of embolic events. Atrial fibrillation recurrences contributed to the models as time-dependent covariates, with patients entering the AF risk class at the time of the first AF episode. Models were adjusted for other known embolism predictors.

Comparisons of continuous variables were performed by two-tailed unpaired Student t test for normally distributed variables and by Mann-Whitney test for variables with skewed distribution. Comparisons of categorical variables were performed by means of Fisher exact test for extreme proportions or chi-square otherwise.

Curves for survival to embolic events were calculated using the Kaplan-Meier method and displayed for the entire patient population and for patients subgroups selected as a function of AF recurrence in the follow-up. Kaplan-Meier curves comparison was performed by log-rank test. All reported p values are two-tailed. SPSS software (version 11.5 statistical package, SPSS Inc., Chicago, Illinois) was used for all the statistical analysis.

	Results

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Between September 1999 to December 2003, 725 patients were enrolled in 83 cardiology departments (Appendix) after they received a DDDR pacemaker (AT500, Medtronic Inc.). Pacing indication was sinus node disease in 600 (82.8%) patients, atrioventricular block in 34 (4.7%) patients, drug-induced bradycardia in 32 (4.4%) patients, other in 59 (8.1%) patients. A review of patients clinical characteristics is shown in Table 1.

View larger version (17K): [in this window] [in a new window]   Figure 1 Kaplan-Meier cumulative survival from embolic events.

Results of univariate and multivariate analysis are shown in Table 2. Among patient baseline characteristics, univariate analysis associated ischemic heart disease, prior embolic events, diabetes, hypertension, and anticoagulant use as those associated with a significantly higher risk of embolic events. Furthermore, for each additional stroke risk factor, we observed an increase by a factor of 2.7 in the risk of embolic events. Multivariate logistic analysis showed that embolic events are independently associated with ischemic heart disease (7.0 OR, 95% CI 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). Cox multivariate analysis, adjusted for previously shown embolism predictors, demonstrated that the occurrence of AF episodes longer than one day was independently associated with arterial embolism (3.1 hazard ratio, 95% CI 1.1 to 10.5, p = 0.044). Occurrence of AF episodes longer than 5 min was not associated with a significantly higher risk of embolic events.

View larger version (15K): [in this window] [in a new window]   Figure 2 Kaplan-Meier cumulative survival from embolic events for patients with atrial fibrillation (AF) episodes longer than one day and for patients without AF recurrences or with AF episodes shorter than one day.

The distribution of enrolled patients, of patients treated with antiplatelet agents, of patients treated with anticoagulation therapy, of patients who suffered embolic events, and the distribution of embolism annual rate is shown in Table 4 as a function of the number of embolism risk factors exhibited at baseline. During follow-up, anticoagulation therapy was started in two patients at the time of embolic events.

	Discussion

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Main study findings.   This study is the first to report on embolic events during a long-term follow-up (1,166 patient-years) on a large cohort of patients paced for bradycardia, suffering from AF, and implanted with a pacemaker capable of atrial therapies delivery. About 36% of the patients were anticoagulated with warfarin and acenocumarol according to the usual clinical practice (23).

Our data confirm that prior embolism, ischemic cardiopathy, hypertension, diabetes mellitus, and the presence of any stroke risk factor are independently associated with embolic events.

Furthermore, our results show that, in a population of pacemaker patients suffering from AF, device-detected AF recurrences longer than one day are independently associated with embolic events. Atrial fibrillation duration longer than one day could certainly be a simple parameter to be used in clinical practice to guide anticoagulation therapy.

Arterial embolism annual rates.   Embolic risk has been extensively studied in the general population of patients with AF treated with conventional pharmacological agents (6,7,24,25). On the other hand, only limited and recent data are available (3,15) about patients with bradycardia and coexisting AF. Our data show a yearly incidence of arterial embolism in general and of ischemic stroke in particular of 1.2% and 0.6%, respectively.

Investigators of the Canadian Trial Of Physiologic Pacing (CTOPP) (3) enrolled 2,568 patients and observed an annual stroke rate of 1.1% in the patient group with ventricular pacing and of 1.0% in the group with physiological pacing. Investigators of the MOST study (15) observed an annual rate of ischemic stroke equal to 1.4%, with no clear differences according to pacing mode.

Anticoagulant therapy may explain the observation of a lower annual rate for stroke observed in our study compared with the MOST study (15). As a matter of fact, 32% of patients in our study and 24% in the MOST study had anticoagulant therapy. The percentage of anticoagulated patients (34%) in the CTOPP study (3) was similar to ours. An alternative hypothesis could be that atrial pacing, with preventive algorithms and/or antitachycardia therapies, may have some protective action against thromboembolism, by preventing or suppressing AF triggers and terminating regular and slow atrial tachyarrhythmias. There are no published data to support this hypothesis, which should be tested in a prospective randomized trial. Unfortunately, such a study would require in practice a very large sample size, due to the very low expected event rate (3,15) and to the possible occurrence in an elderly population of stroke with etiologies other than left atrium cardiogenic embolism (which may be hypothetically affected by atrial pacing), such as left ventricle embolism, carotid and aortic atherosclerosis, or hypoperfusion of small arteriolar beds.

Predictors of embolic events.   Previous studies (25,26) about AF patients without bradycardia identified ischemic cardiopathy, hypertension, diabetes mellitus, increasing age, previous TIA or stroke, heart failure, low ventricular function, and large left atrium dimensions as independent predictors of stroke. Our data confirm that ischemic cardiopathy, hypertension, diabetes mellitus, and prior embolism are independently associated with embolic events for our population.

Embolic events and AF.   The percentage of patients with device-detected AF recurrences longer than one day was significantly higher among patients who suffered arterial embolism than among patients without embolism. Multivariate analysis, adjusted for embolism prognostic factors, demonstrated that patients with AF recurrences longer than one day were 3.1 x more likely to suffer arterial embolism. Finally, Kaplan-Meier survival analyses showed that embolic events were significantly more frequent in patients with AF episodes longer than one day when compared with patients without AF or with shorter AF recurrences. Glotzer et al. (16) recently showed that device-detected AF episodes longer than 5 min are associated with a two-fold increase in risk of death or stroke. In our results occurrence of AF episodes longer than 5 min was not associated with higher embolic risk: this is probably due to the fact that in our patient population (i.e., bradycardia patients with history of frequent symptomatic AF episodes) short AF recurrences were very common, occurring in about 80% of our patients. Considering the results of the present study, and the findings by Glotzer et al. (16), antithrombotic therapy should be considered in patients with device-detected AF recurrences.

Clinical implications of our study.   Greenspon et al. (15) showed a higher risk of embolism in patients found in AF during follow-up visits. There could be important limitations associated to limiting the selection of clinically evident AF (i.e., symptomatic or discovered by chance during a routine follow-up) as a supplementary risk factor to guide anticoagulant therapy, because patients may be exposed to the risk of embolism by persistent asymptomatic and undetected AF episodes. Our results show that, in patients paced for bradycardia and suffering from frequent AF recurrences, simple device daily diagnostics showing the time spent in AF could be useful to guide anticoagulant therapy. In particular, it could suggest that the clinician start anticoagulation in patients with no other risk factors but with long periods of arrhythmia, or to request accurate international normalized ratio control, or to add antiplatelet drugs to anticoagulant agents in specific patients. Device diagnostic capabilities may be of particular importance in pacemaker patients because pacing often results in rate smoothing, usually decreasing patients’ symptomaticity.

Embolism and risk factors.   Our data show that embolism occurred only in patients with stroke risk factors, that embolism risk is directly correlated to the number of risk factors, and finally that the yearly incidence of embolism is <1% in patients with 1 risk factor and increases as a function of the number of cardiac or noncardiac risk factors.

Embolism and antithrombotic therapy.   Warfarin has been shown as highly effective, in particular more effective than antiplatelet agents, in preventing stroke in patients with AF in several randomized trials (24,26–28), most likely by minimizing the formation of atrial thrombi.

Guidelines about antithrombotic therapy recommend preventive oral anticoagulation in patients with valvular heart disease, in patients 65 years old, or in the presence of additional risk factors for thromboembolic events (23).

Among 14 patients who suffered arterial embolism, 9 were on anticoagulant therapy, even if we cannot state if international normalized ratio values were in the expected range at the time of embolic events.

The choice of antithrombotic treatment in this study was left to the decision of the attending cardiologists who are used to managing anticoagulation therapy. The percentage of patients on antiplatelet therapy, but not the percentage of patients on anticoagulant agents, increased as a function of patient stroke risk factors.

Among patients indicated for anticoagulation, those who actually were on anticoagulant agents were only 32.2% at baseline and 41.2% at the end of the follow-up. This percentage is lower than those described in previous studies (29–34) outlining an important underutilization of anticoagulation therapy. However, in the arterial embolic group, the percentage of anticoagulated patients was up to 64%, which is average for this patient population (Table 1).

Study limitations.   The incidence of some embolic events, such as asymptomatic ischemic attacks, could have been underestimated because no systematic neurological imaging procedures were requested by the study. Underestimation of the embolism risk, associated to AF episodes or other known stroke risk factors, cannot be excluded because the patients with the greatest numbers of risk factors were also selected for anticoagulation by their clinicians.

Low frequency of embolic events leaves considerable room for statistical error associated with the estimation of arterial embolism annual rate or risk associated with predictors of embolic events. Our study did not record systematically the level of anticoagulation, which was left to the attending cardiologist; therefore, we cannot discuss the adequate anticoagulation level at the time of stroke. This study did not collect information about contraindications to the anticoagulation therapy; therefore, we were only able to observe the low use of anticoagulation agents in the referred patients.

Our data should be limited to this studied population.

Conclusions.   Our study is the first to report thromboembolic complications on a long-term follow-up of a large cohort of patients paced for bradycardia and suffering from AF, and therefore implanted with a pacemaker capable of atrial therapies delivery. Our data show a 0.6% annual stroke incidence and a 1.2% annual incidence of embolism in general. Prior embolism, ischemic cardiopathy, hypertension, diabetes mellitus, and, in general, the presence of stroke risk factors resulted in the association of higher risk of embolism in the observation period.

Patients with device-detected AF recurrences longer than one day had a risk of embolism 3.1 times increased as compared to patients without or with shorter AF recurrences, showing that AF recurrences longer than one day are independently associated with arterial embolism. Anticoagulation therapy was underused in our patient population; moreover, arterial embolic events were observed also in anticoagulated patients. This datum suggests either a stricter international normalized ratio monitoring or an addition of antiplatelet therapy.

	Appendix

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For a list of the investigators and centers participating in the Italian AT500 Registry, please see the online version of this article.

	Acknowledgments

 
The authors thank Tiziana DeSanto, Paola DiStefano, Daniela Fabrizi, Massimiliano Pepe, Rita Ianni, and Fabiola Zanna for their expert assistance in data management and statistical analysis.

	Footnotes

 
Elena Mazzini, Marco Vimercati, and Dr. Andrea Grammatico are employees of Medtronic, Inc.

	References

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1. Mattioli AV, Castellani ET, Vivoli D, Sgura FA, Mattioli G. Prevalence of atrial fibrillation and stroke in paced patients without prior atrial fibrillationa prospective study. Clin Cardiol 1998;21:117-122.[ISI][Medline]
2. Andersen HR, Thuesen L, Baggar JP, Vesterlund T, Thomsen PEB. Prospective randomized trial of atrial versus ventricular pacing in sick sinus syndrome Lancet 1994;344:1523-1528.[CrossRef][ISI][Medline]
3. Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes N Engl J Med 2000;342:1385-1391.[Abstract/Free Full Text]
4. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual chamber pacing for sinus node dysfunction N Engl J Med 2002;346:1854-1860.[Abstract/Free Full Text]
5. Benjamin EJ, Wolff PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of deaththe Framingham Heart study. Circulation 1995;92:835-841.[Abstract/Free Full Text]
6. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for strokethe Framingham study. Stroke 1991;22:983-988.[Abstract/Free Full Text]
7. Britton M, Gustafsson C. Non-rheumatic atrial fibrillation as a risk factor for stroke Stroke 1985;16:182-188.[Abstract/Free Full Text]
8. Bogousslavsky J, Van Melle G, Regli F, Kappenberger L. Pathogenesis of anterior circulation stroke in patients with nonvalvular atrial fibrillationthe Lausanne Stroke registry. Neurology 1990;40:1046-1050.[Abstract/Free Full Text]
9. Manning WJ, Silverman DI, Waksmonski CA, Oettgen P, Douglas PS. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation Arch Intern Med 1995;155:2193-2198.[Abstract]
10. Petersen P, Godtfredsen J. Embolic complications in paroxysmal atrial fibrillation Stroke 1986;17:622-626.[Abstract/Free Full Text]
11. Albers GW. Atrial fibrillation and stroke Arch Intern Med 1994;154:1443-1448.[Abstract]
12. Fairfax AJ, Lambert CD, Leatham A. Systemic embolism in chronic sinoatrial disorder N Engl J Med 1976;295:190-192.[Abstract]
13. Bathen J, Sparr S, Rokseth R. Embolism in sinoatrial disease Acta Med Scand 1978;203:7-11.[ISI][Medline]
14. Fisher M, Kase CS, Stelle B, Mills Jr RM. Ischemic stroke after pacemaker implantation in sick sinus syndrome Stroke 1988;19:712-715.[Abstract/Free Full Text]
15. Greenspon AJ, Hart RG, Dawson D, et al. Predictors of stroke in patients paced for sick sinus syndrome J Am Coll Cardiol 2004;43:1617-1622.[Abstract/Free Full Text]
16. Glotzer TV, Hellkamp AS, Zimmerman J, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke Circulation 2003;107:1614-1619.[Abstract/Free Full Text]
17. Gregoratos G, Cheitlin MD, Conill A, et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devicesexecutive summary—a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). Circulation 1998;97:1325-1335.[Free Full Text]
18. Israel CW, Hugl B, Unterberg C, et al. Pace-termination and pacing for prevention of atrial tachyarrhythmiasresults from a multicenter study with an implantable device for atrial therapy. J Cardiovasc Electrophysiol 2001;12:1121-1128.[CrossRef][ISI][Medline]
19. Lee MA, Weachter R, Pollak S, et al. The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias J Am Coll Cardiol 2003;41:1926-1932.[Abstract/Free Full Text]
20. Swerdlow CD, Schöls W, Dijkman B, et al. Detection of atrial fibrillation and flutter by a dual chamber implantable cardioverter-defibrillator Circulation 2000;101:878-885.[Abstract/Free Full Text]
21. Wilkoff BL, Kuhlkamp V, Volosin K, et al. Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detectionresults and technical considerations. Circulation 2001;103:381-386.[Abstract/Free Full Text]
22. Pollack WM, Simmons JD, Interian A, et al. Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial fibrillation and flutter Pacing Clin Electrophysiol 2001;24:424-429.[CrossRef][Medline]
23. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary: 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology Circulation 2001;104:2118-2150.[Free Full Text]
24. Atrial Fibrillation Investigators: AFAAS, BAATAFS, CAFAS, SPAFS, and VASPNAFS Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillationanalysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449-1457.[Abstract]
25. The Stroke Prevention in Atrial Fibrillation Investigators Predictors of thromboembolism in atrial fibrillation. I. Clinical features of patients at risk Ann Intern Med 1992;116:1-5.[ISI][Medline]
26. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillationa metaanalysis. Ann Intern Med 1999;131:492-501.[Abstract/Free Full Text]
27. Stroke Prevention in Atrial Fibrillation Investigators Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillationStroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996;348:633-638.[CrossRef][ISI][Medline]
28. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation N Engl J Med 1996;335:540-546.[Abstract/Free Full Text]
29. Stafford R, Singer D. Recent national patterns of warfarin use in atrial fibrillation Circulation 1998;97:1231-1233.[Abstract/Free Full Text]
30. Perez I, Melbourn A, Kalra L. Use of antithrombotic measures for stroke prevention in atrial fibrillation Heart 1999;82:570-574.[Abstract/Free Full Text]
31. Cohen N, Amoznino-Sarafian D, Alon I, et al. Warfarin for stroke prevention still underused in atrial fibrillation Stroke 2000;31:1217-1222.[Abstract/Free Full Text]
32. Bungard T, Ghali W, Teo K, et al. Why do patients with atrial fibrillation not receive warfarin? Arch Intern Med 2000;160:41-46.[Abstract/Free Full Text]
33. Weisbord SD, Whittle J, Brooks RC. Is warfarin really underused in patients with atrial fibrillation? J Gen Intern Med 2001;11:743-749.
34. Blanch P, Freixa R, Ibernon M, et al. Use of oral anticoagulants in patients discharged with atrial fibrillation in 2000 Rev Esp Cardiol 2003;56:1057-1063.[CrossRef][ISI][Medline]

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				R. Nieuwlaat, A. Capucci, G. Y.H. Lip, S. B. Olsson, M. H. Prins, F. H. Nieman, J. Lopez-Sendon, P. E. Vardas, E. Aliot, M. Santini, et al. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation Eur. Heart J., December 2, 2006; 27(24): 3018 - 3026. [Abstract] [Full Text] [PDF]

				M. Gulizia, S. Mangiameli, S. Orazi, G. Chiaranda, G. Boriani, G. Piccione, N. DiGiovanni, A. Colletti, C. Puntrello, G. Butera, et al. Randomized comparison between Ramp and Burst+ atrial antitachycardia pacing therapies in patients suffering from sinus node disease and atrial fibrillation and implanted with a DDDRP device Europace, July 1, 2006; 8(7): 465 - 473. [Abstract] [Full Text] [PDF]

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