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Archives of cardiovascular diseases
Volume 105, n° 4
pages 226-238 (avril 2012)
Doi : 10.1016/j.acvd.2011.11.005
Received : 27 July 2011 ;  accepted : 16 November 2011
Rate versus rhythm control in atrial fibrillation and clinical outcomes: Updated systematic review and meta-analysis of randomized controlled trials
Contrôle de la fréquence ou du rythme cardiaque dans la fibrillation atriale : méta-analyse des études randomisées contrôlées
 

Daniel Caldeira a, Cláudio David a, , b , Cristina Sampaio a, c
a Laboratory of Clinical Pharmacology and Therapeutics, School of Medicine, University of Lisbon, Lisbon, Portugal 
b Departement of Cardiology, Santa Maria University Hospital, Lisbon, Portugal 
c Institute de Molecular Medicine, Lisbon, Portugal 

Corresponding author. Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas-Moniz, 1649-028 Lisbon, Portugal.
Summary

Atrial fibrillation is the most frequently occurring sustained cardiac arrhythmia and is associated with a significantly increased risk of thromboembolic events and death. We sought to compare the clinical efficacy of rate and rhythm control strategies in patients with non-postoperative atrial fibrillation. We searched the PubMed database and the Cochrane Central Register of Controlled Trials for randomized controlled trials comparing rate versus rhythm control in patients with atrial fibrillation. Studies were retrieved and we analysed major clinical outcomes. Risk ratios (RRs) and 95% confidence intervals were calculated assuming random effects due to the clinical heterogeneity of the study populations. Eight randomized controlled trials were identified, with a total of 7499 patients with atrial fibrillation. There were no significant differences in the effects of rate and rhythm control on any outcome: all-cause mortality (RR: 0.95; CI: 0.86–1.05), cardiovascular mortality (RR: 0.99; CI: 0.87–1.13), arrhythmic/sudden death (RR: 1.12; CI: 0.91–1.38), ischaemic stroke (RR: 0.89; CI: 0.52–1.53), systemic embolism (RR: 0.89; CI: 0.69–1.14) and major bleeding (RR: 1.10; CI: 0.89–1.36). Updated data pooled from a large population of patients with atrial fibrillation suggests that rate and rhythm control strategies have similar effects on major clinical outcomes. Other factors, including individual preferences, comorbidities, drug tolerance and cost issues, should be considered when choosing the approach for these patients.

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Résumé

La fibrillation atriale est l’arythmie cardiaque soutenue la plus fréquente et est associée avec une augmentation du risque de complication thromboembolique et de décès. Notre objectif a été de comparer l’efficacité clinique des stratégies contrôles du rythme versus contrôle de la fréquence cardiaque chez des patients en fibrillation atriale en excluant la phase postopératoire. Notre recherche a été centrée sur les bases de données PubMed et CENTRAL, avec les mots clés « essais randomisés contrôlés » comparant les stratégies de contrôle de la fréquence du rythme cardiaque chez les patients en fibrillation atriale. Les études ont été analysées pour ce qui concerne les évènements cliniques majeurs. Le risque relatif et les intervalles de confiance à 95 % ont été calculés, en retenant l’hypothèse d’effets au hasard dus à l’hétérogénéité clinique des populations incluses dans les différentes études. Huit essais randomisés contrôlés ont été identifiés, incluant un total de 7499 patients en fibrillation atriale. Il n’y avait pas de différence significative entre les deux stratégies pour ce qui concerne le taux de mortalité globale (RR : 0,95 ; IC 95 % : 0,86–1,05), la mortalité cardiovasculaire (RR : 0,99 ; IC 95 % : 0,87–1,13), la mort subite ou arythmique (RR : 1,12 ; IC 95 % : 0,91–1,38), le taux d’accident ischémique cérébral (RR : 0,89 ; IC 95 % : 0,52–1,53), d’embolie systémique (RR : 0,89 ; IC 95 % : 0,69–1,14) et le taux de saignement majeur (RR : 1,10 ; IC 95 % : 0,89–1,36). Cette méta-analyse, mise à jour des précédentes, basée sur une population importante de patients en fibrillation atriale suggère que les deux stratégies: contrôle du rythme ou de la fréquence cardiaque dans la fibrillation atriale, ont des effets similaires sur les évènements cardiovasculaires majeurs. D’autres facteurs prenant en considération les préférences individuelles, les comorbidités, la tolérance des médicaments ou encore les coûts devraient être pris en considération lorsqu’une des deux stratégies est retenue dans la prise de ces patients.

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Keywords : Adrenergic beta-antagonists, Calcium-channel blockers, Digitalis, Antiarrhythmia agents, Atrial fibrillation

Mots clés : Bêtabloquants, Antagonistes calciques, Digitaliques, Agents antiarythmiques, Fibrillation atriale

Abbreviations : AF, AFFIRM, AF-CHF, CAFÉ-II, CI, HOT CAFÉ, J-RHYTHM, PIAF, RACE, RCT, RR, STAF


Introduction

AF is the most common sustained cardiac arrhythmia. Risk factors for this condition include male sex, smoking, heart failure, diabetes, arterial hypertension, left ventricular hypertrophy, valvular heart disease, myocardial infarction and advanced age. The lifetime risk of developing AF in subjects aged greater than 40 years is around 25% [1, 2].

AF is associated with increased cardiovascular morbidity and mortality. In addition to the deleterious haemodynamic effects that can trigger or worsen heart failure, AF also predisposes to thromboembolic events; stroke incidence increases with age, with the 5-year risk rising from 1.5% in the 6th decade of life to 23.5% in those aged more than 80 years [3]. AF is an independent risk factor for death [4].

The pharmacological treatment of AF follows one of two strategies: rate control (controlling the ventricular rate with beta-blockers, non-dihydropyridine calcium-channel blockers and/or digitalis); or rhythm control (restoring and maintaining sinus rhythm with electrical cardioversion and/or antiarrhythmic agents) [5]. Rhythm control maintenance with antiarrhythmic drugs can improve symptoms and reduce the incidence of stroke but may lead to an increased risk of adverse events due to negative inotropic and proarrhythmic effects [6]. The rate control strategy may have fewer adverse events [7]. Antithrombotic agents are usually used to prevent thromboembolic events in association with rate control drugs, whereas their use after sinus rhythm is restored in rhythm control depends on the patient’s risk factors.

Our aim was to systematically review RCTs and compare the relative effects of rate and rhythm control in AF. We proposed to analyse clinically relevant outcomes: all-cause mortality, cardiovascular mortality, arrhythmic/sudden death, ischaemic stroke, systemic embolism and major bleeding.

Methods
Searching

A search strategy was developed in September 2011 using the PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases for study identification. There were no language limitations. References of obtained studies were also comprehensively searched.

The electronic search for RCT publication type was undertaken using the following keywords: rate, beta-blocker, acebutolol, atenolol, bisoprolol, carvedilol, esmolol, metoprolol, nadolol, pindolol, propranolol, timolol, calcium-channel blocker, verapamil, diltiazem, digitalis, digoxin, rhythm, amiodarone, sotalol, propafenone, disopyramide, dofetilide, flecainide, ibutilide, dronedarone and azimilide, mortality, death, stroke, embolism, thromboembolic, thromboembolism, bleeding and atrial fibrillation. Boolean operators AND and OR were used to combine terms. Postoperative and postpercutaneous intervention studies were excluded from the search using the Boolean operator NOT.

Selection

We included RCTs comparing pharmacological approaches to maintaining rate or rhythm control in patients with AF. Quasi-randomized studies and prospective cohorts were not included. The patients’ mean age had to be greater than 55 years due to the low risk of death or stroke in patients with AF under this age [4, 8]. To determine the efficacy of the interventions as primary strategies, the trials had to have intention-to-treat analysis or provide data that allowed this type of calculation. The analysed outcomes were all-cause mortality, cardiovascular mortality, arrhythmic/sudden death, ischaemic stroke, systemic embolism (combining ischaemic stroke and other systemic embolic events) and major bleeding.

Validity assessment

The PEDro score was used to assess the methodological quality of data reporting in the studies [9]. This score is based on the presence/absence of 11 items: eligibility criteria, random allocation, allocation concealment, similar baseline characteristics, blinding of all subjects, blinding of therapists, blinding of outcome assessors, crossover rate less than 15%, intention-to treat analysis, statistical comparisons between groups and measures of variability.

Data abstraction

Studies that met the criteria outlined above were assessed by one review author and checked by another. AF population, study size, follow-up, primary outcome, demographic characteristics and comorbidities were retrieved. Anticoagulation therapy, and rate and rhythm interventions were also sought. Data entry into software was also double checked. All disagreements were solved by consensus.

Quantitative data synthesis

The statistical analyses were performed using the RevMan software (version 5.1.4) provided by the Cochrane Collaboration when more than one trial had data for pooled analysis. Dichotomous outcomes were analysed by the Mantel-Haenszel method. RR and 95% CI were calculated. When zero cells were present in one arm, RevMan automatically added 0.5 to them to perform the calculations. The results estimates were based on a fixed-effects model or a random effects model, depending on heterogeneity. Statistical heterogeneity was assumed if I2was greater than 50%. Clinical heterogeneity was analysed by authors according to clinical differences between study patients. Publication bias assessment with a funnel plot was planned if more than 10 studies were retrieved.

Sensitivity analysis was planned according to baseline heart failure, age, anticoagulation treatment, mean follow-up and study size.

Results

One hundred and fifty-seven studies were found in the database search and 146 studies were excluded: 11 were not RCTs; 36 were not AF studies; 73 citations reported trials that did not compare pharmacological rate versus rhythm control in AF; and 26 records were substudies of eligible trials. Eleven RCTs remained and three were excluded due to lack of data necessary for analysis based on intention-to-treat.

Eight RCTs were included for meta-analysis [10, 11, 12, 13, 14, 15, 16, 17]. Data not provided in the main papers were sought from the RACE and AFFIRM post-hoc studies (Figure 1) [18, 19].



Figure 1


Figure 1. 

Flowchart of study selection for meta-analysis. AF: atrial fibrillation; CENTRAL: Cochrane Central Register of Controlled Trials; RCTs: randomized controlled trials.

Zoom

Included studies enrolled a total of 7499 AF patients with a mean age of 68 years. In all these trials the majority of patients were men (63.4–82.0%). Prevalence of hypertension ranged from 42.8 to 64.3%, valvular disease from 4.9 to 17% and coronary disease from 7.4% to 43.5%. The AF-CHF study and the CAFÉ-II study included only heart failure patients. The PIAF study provided no heart failure data. In the other trials, the prevalence of heart failure ranged from 3.6 to 70%. Weighted mean follow-up was 2.9 years, ranging from 1 year (PIAF) to 3.5 years (AFFIRM).

The PEDro quality score (scale range 1–11) for the obtained trials varied between 6 and 7. None of the trials described allocation concealment methods and interventions were unblinded for patients and physicians. The RACE study was the only one that reported blinding of the researchers who recorded the outcomes. The PIAF and RACE studies had differences in relevant baseline characteristics. The AFFIRM and AF-CHF studies and the J-RHYTHM had crossover rates greater than 15%. Table 1 details the main characteristics of each study and Table 2 contains their conclusions.

Rate and rhythm control showed no statistical heterogeneity in any outcome. The I2test was 0% for all outcomes, with the exception of ischaemic stroke, which reported an I2of 26%. However, the authors stated that the existence of clinical heterogeneity was due to differences in the patients included in the studies. The different types of AF (paroxysmal and persistent), the existence of studies that included heart failure patients exclusively and the different therapeutic combinations/sequences used in the rate and rhythm control strategies led us to choose the random effects model for pooled analysis. A funnel plot for publication bias analysis was not done because it is not recommended when fewer than 10 studies are analysed [20].

All-cause mortality was assessed in all trials and no intervention showed significant superiority in any individual study. To determine the overall effect, a meta-analysis was done and the calculated death RR was 0.95 (95% CI: 0.86–1.05) (Figure 2). In six trials with a total of 6615 patients, the cardiovascular mortality RR was 0.99 (95% CI: 0.87–1.13) (Figure 3).



Figure 2


Figure 2. 

Forest plot for all-cause mortality. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; AF-CHF: Atrial Fibrillation and Congestive Heart Failure study; CAFÉ-II: controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure; CI: confidence interval; HOT CAFÉ: How to Treat Chronic Atrial Fibrillation study; J-RHYTHM: Japanese Rhythm Management Trial for Atrial Fibrillation; M-H: Mantel-Haenszel; PIAF: Pharmacological Intervention in Atrial Fibrillation study; RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom



Figure 3


Figure 3. 

Forest plot for cardiovascular mortality. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; AF-CHF: Atrial Fibrillation and Congestive Heart Failure study; CAFÉ-II: controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure; CI: confidence interval; HOT CAFÉ: How to Treat Chronic Atrial Fibrillation study; M-H: Mantel-Haenszel; PIAF: Pharmacological Intervention in Atrial Fibrillation study; RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom

The arrhythmic/sudden death RR was 1.12 (95% CI: 0.91–1.38) among 6410 patients in five studies (Figure 4). Ischaemic stroke data was retrieved from four trials with a total of 5288 patients, with a pooled analysis RR of 0.89 (95% CI: 0.52–1.53) (Figure 5). Six trials with 6062 patients evaluated systemic embolism (which included ischaemic strokes and other systemic embolic events) and the RR was 0.89 (95% CI: 0.69–1.14) (Figure 6). Major bleeding also showed no significant differences in results pooled from five RCTs that enrolled 5810 patients; the RR was 1.10 (95% CI: 0.89–1.36) (Figure 7). Table 3 presents a summary of the findings.



Figure 4


Figure 4. 

Forest plot for arrhythmic/sudden death mortality. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; AF-CHF: Atrial Fibrillation and Congestive Heart Failure study; CI: confidence interval; M-H: Mantel-Haenszel; PIAF: Pharmacological Intervention in Atrial Fibrillation study; RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom



Figure 5


Figure 5. 

Forest plot for ischaemic stroke. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; CI: confidence interval; HOT CAFÉ: How to Treat Chronic Atrial Fibrillation study; J-RHYTHM: Japanese Rhythm Management Trial for Atrial Fibrillation; M-H: Mantel-Haenszel; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom



Figure 6


Figure 6. 

Forest plot for systemic embolism. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; AF-CHF: Atrial Fibrillation and Congestive Heart Failure study; CI: confidence interval; HOT CAFÉ: How to Treat Chronic Atrial Fibrillation study; J-RHYTHM: Japanese Rhythm Management Trial for Atrial Fibrillation; M-H: Mantel-Haenszel; PIAF: Pharmacological Intervention in Atrial Fibrillation study; RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom



Figure 7


Figure 7. 

Forest plot for major bleeding. AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management study; CI: confidence interval; HOT CAFÉ: How to Treat Chronic Atrial Fibrillation study; J-RHYTHM: Japanese Rhythm Management Trial for Atrial Fibrillation; M-H: Mantel-Haenszel; RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study; STAF: Strategies of Treatment of Atrial Fibrillation study.

Zoom

A sensitivity analysis was done according to variables such as heart failure, mean age, anticoagulation treatment, mean follow-up period and study size, as shown in Table 4. Pooled systemic embolic events were significantly less frequent with rate control when trials with more than 50% of patients with heart failure were analysed. The PIAF, AFFIRM and J-RHYTHM studies were excluded for this reason. The RR was 0.43 (95% CI: 0.21–0.89).

Discussion

This systematic review with meta-analysis was done to assess the direction, size and consistency of effects across RCTs comparing rate versus rhythm control in AF.

In a previous meta-analysis, rate and rhythm control strategies were not significantly different in terms of mortality but a trend towards rate control was observed in patient survival (odds ratio 0.87 [95% CI: 0.74–1.02]; P =0.09) [21]. Statistically significant results favouring rate control with regard to a mortality-stroke composite have been reported in another meta-analysis (odds ratio 0.84 [95% CI: 0.73–0.98]; P =0.02) [22]. Under these circumstances and with new RCTs, it is important to clarify which is the best treatment strategy according to the best available evidence. Our meta-analysis included these new RCTs and provides updated results that answer with more powered information whether rate or rhythm control is better for treating these patients.

None of the strategies showed superiority in the outcomes assessed. Although the results of individual studies did not show clear differences, the performance of the meta-analysis ensured the consistency of findings for a large population, especially when approaching very important clinical outcomes.

Despite the cardiovascular consequences of AF, we considered it important to assess all-cause mortality to include possible non-cardiovascular deaths caused by antiarrhythmic drugs. Amiodarone, which can induce pulmonary toxicity, was prescribed to most patients in four of the six trials that reported data on antiarrhythmic agent use (Table 1). In the AFFIRM analysis of cause-specific mortality, non-cardiovascular deaths were mainly due to pulmonary diseases and lung cancer. Pneumonia was the most common cause of pulmonary death in both interventions. Pulmonary toxicity of amiodarone was the cause of death in only three of 39 patients in the rhythm intervention who died due to lung diseases [19]. The incidence of this effect may be more important, as AF needs to be treated longer than the mean follow-up of this study and the long-term incidence of amiodarone toxicity events is likely to be higher.

Cardiovascular mortality was 63% of the total mortality of all trials and the incidence of this outcome was shown to be independent of the intervention strategy. In AFFIRM, arrhythmias were the main cause of cardiovascular mortality, probably due to the high incidence of atherosclerotic risk factors and ischaemic heart disease in patients with AF [19, 23]. In a post-hoc analysis of the RACE trial, myocardial infarction history was the baseline characteristic more frequently associated with sudden deaths [18]. The two therapeutic strategies were not significantly different with regard to arrhythmic/sudden death, although there was a slight tendency favouring rhythm control; this was surprising because beta-blockers (used in 41% and 68.1% of RACE and AFFIRM rate control patients, respectively) have been shown to prevent sudden death in patients with previous myocardial infarction [24]. Nevertheless, AF subgroup analysis of the US Carvedilol Heart Failure Trials Program showed that these drugs had no advantage in reducing mortality in these patients [25]. Antiarrhythmics used to restore and maintain sinus rhythm have been shown previously to be ineffective in sudden death prevention [27, 26]. However, an increase in arrhythmic/sudden death adverse effect was not observed and a trend towards rhythm control preventing this outcome was seen.

AF itself can be considered as a prothrombotic state and cumulative thrombotic risk factors play an important role in these patients [28, 29]. Rate control groups had protocols that favoured the maintenance of anticoagulant therapy. At the end of all studies, with exception of J-RHYTHM, the rhythm control group had fewer anticoagulated patients than the rate control sample. Recurrence of AF and anticoagulation withdrawal may explain the trend favouring rate control in ischaemic stroke and systemic embolism outcomes. Vitamin K antagonists were the chosen drugs for anticoagulation. These drugs have a narrow therapeutic window with major bleeding incidence rates ranging from 1.4 to 13 per 100 patient-years [30]. Major bleeding incidence was not different between the interventions but there was a tendency favouring rhythm control; this was expected because anticoagulant therapy is a well-known risk factor for bleeding and rate control patients were more frequently treated with anticoagulants.

Sensitivity analysis showed that rate control was better at preventing embolic events in a pooled analysis of studies with more than 50% of patients with heart failure. Heart failure is a component of the CHADS2 score and adequate anticoagulation may have produced this result favouring rate control. A pooled analysis of results from the HOT CAFÉ, STAF and RACE studies was done. None of these trials had both arms anticoagulated during study follow-up. In these studies, rhythm control patients were less likely to receive oral anticoagulation. As AF may have a structural origin and arrhythmia recurrence is frequent, premature or inadequate withdrawal of oral anticoagulants in the rhythm control arm could have predisposed towards thromboembolic events. More recently, AF-CHF, an RCT that exclusively analysed patients with heart failure with both rate and rhythm control arms under anticoagulation, showed that stroke was similar between interventions (hazard ratio 0.74 [95% CI: 0.40–1.35]).

Eight RCTs were included in the meta-analysis, but most of the statistical weight came from AFFIRM and AF-CHF. A sensitivity analysis excluding these trials was done. A pooled analysis of the smaller studies showed the same result as the primary analysis (Table 4). It is interesting that when trials with a mean patient age less than 65 years were analysed, there was a trend towards rate control. The analysed population may not be sufficiently young to be representative of younger/middle-aged symptomatic patients, for whom the primary policy would be to restore and maintain sinus rhythm.

In the absence of a clear benefit for one intervention in the analysed outcomes, other factors should be considered for strategy choice, such as individual preferences, comorbidities, drug tolerance and cost issues; regarding this last factor, cost-effectiveness studies favoured the rate control strategy [31, 32, 33].

Implications for clinical practice and research

All-cause mortality and cardiovascular mortality analysis showed no trend towards either intervention and had small CIs. In the other outcomes, with larger CIs, there was a tendency for rate control to be better in the prevention of ischaemic stroke and systemic embolism, while prevention of arrhythmic/sudden death and major bleeding tended towards rhythm control. These last data were not statistically significant but can be clinically relevant when applied to the individual patient, tailoring the approach according to their characteristics.

Limitations

This review includes a meta-analysis of RCTs. Results were pooled from reported outcomes and not from individual patient data, which is a potential source of bias in this type of analysis.

Heterogeneity of clinical characteristics and interventions across the various studies are important limitations despite the random effects method used in quantitative analysis.

All RCTs included in this meta-analysis were unblinded. This may be explained by the physical nature of electrical cardioversion that is very distinct from rate control standard procedures. The use of fake electrical cardioversion for blinding would raise ethical issues and would interfere with other outcomes measured in some studies, such as quality of life and number of hospitalizations.

In the arrhythmic/sudden death outcome, we included presumable arrhythmic deaths from AF-CHF, arrhythmic deaths from AFFIRM and sudden deaths from the other trials.

For studies that did not supply data for systemic embolism, the information was calculated by adding ischaemic stroke to systemic embolism. Ischaemic stroke can be either embolic or thrombotic but most ischaemic strokes in AF patients have a cardiac embolic source [34].

Conclusion

In this review, rate and rhythm control options did not differ in terms of all-cause mortality, cardiovascular mortality, arrhythmic/sudden death, ischaemic stroke, systemic embolism and major bleeding. The large population of patients with AF from which quantitative data was obtained allowed us to robustly reinforce the conclusions that rate and rhythm control are similar in terms of clinical outcomes. This supports guidelines’ class I recommendations for rate and rhythm control strategies [35, 36]. Both are acceptable alternatives for patients with AF and the initial clinical choice should be individualized according to patient preferences, AF symptoms, AF recurrence risk, comorbidities, tolerance to antiarrhythmic drugs and expected costs.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

References

Benjamin E.J., Levy D., Vaziri S.M., and al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham heart study JAMA 1994 ;  271 : 840-844
Lloyd-Jones D.M., Wang T.J., Leip E.P., and al. Lifetime risk for development of atrial fibrillation: the Framingham heart study Circulation 2004 ;  110 : 1042-1046 [cross-ref]
Wolf P.A., Abbott R.D., Kannel W.B. Atrial fibrillation as an independent risk factor for stroke: the Framingham study Stroke 1991 ;  22 : 983-988 [cross-ref]
Benjamin E.J., Wolf P.A., D’Agostino R.B., and al. Impact of atrial fibrillation on the risk of death: the Framingham heart study Circulation 1998 ;  98 : 946-952
Page R.L. Clinical practice. Newly diagnosed atrial fibrillation N Engl J Med 2004 ;  351 : 2408-2416 [cross-ref]
Saxonhouse S.J., Curtis A.B. Risks and benefits of rate control versus maintenance of sinus rhythm Am J Cardiol 2003 ;  91 : 27D-32D [inter-ref]
Deneer V.H., Borgh M.B., Kingma J.H., and al. Oral antiarrhythmic drugs in converting recent onset atrial fibrillation Pharm World Sci 2004 ;  26 : 66-78 [cross-ref]
Wang T.J., Massaro J.M., Levy D., and al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham heart study JAMA 2003 ;  290 : 1049-1056 [cross-ref]
Maher C.G., Sherrington C., Herbert R.D., and al. Reliability of the PEDro scale for rating quality of randomized controlled trials Phys Ther 2003 ;  83 : 713-721
Carlsson J., Miketic S., Windeler J., and al. Randomized trial of rate control versus rhythm ontrol in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study J Am Coll Cardiol 2003 ;  41 : 1690-1696 [cross-ref]
Hohnloser S.H., Kuck K.H., Lilienthal J. Rhythm or rate control in atrial fibrillation – pharmacological intervention in atrial fibrillation (PIAF): a randomised trial Lancet 2000 ;  356 : 1789-1794 [cross-ref]
Ogawa S., Yamashita T., Yamazaki T., and al. Optimal treatment strategy for patients with paroxysmal atrial fibrillation: J-RHYTHM study Circ J 2009 ;  73 : 242-248 [cross-ref]
Opolski G., Torbicki A., Kosior D.A., and al. Rate control vs rhythm control in patients with non-valvular persistent atrial fibrillation: the results of the polish how to treat chronic atrial fibrillation (HOT CAFE) study Chest 2004 ;  126 : 476-486 [cross-ref]
Roy D., Talajic M., Nattel S., and al. Rhythm control versus rate control for atrial fibrillation and heart failure N Engl J Med 2008 ;  358 : 2667-2677 [cross-ref]
Shelton R.J., Clark A.L., Goode K., and al. A randomised, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFE-II Study) Heart 2009 ;  95 : 924-930 [cross-ref]
Van Gelder I.C., Hagens V.E., Bosker H.A., and al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation N Engl J Med 2002 ;  347 : 1834-1840 [cross-ref]
Wyse D.G., Waldo A.L., DiMarco J.P., and al. A comparison of rate control and rhythm control in patients with atrial fibrillation N Engl J Med 2002 ;  347 : 1825-1833
Hagens V.E., Rienstra M., Van Veldhuisen D.J., and al. Determinants of sudden cardiac death in patients with persistent atrial fibrillation in the rate control versus electrical cardioversion (RACE) study Am J Cardiol 2006 ;  98 : 929-932 [inter-ref]
Steinberg J.S., Sadaniantz A., Kron J., and al. Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study Circulation 2004 ;  109 : 1973-1980 [cross-ref]
Sterne JAC, Egger M, Moher D. (editors). Chapter 10: Addressing reporting biases. Cochrane Handbook for Systematic Reviews of Intervention. Version 5.0.1 (updated September 2008): The Cochrane Collaboration; 2008. Available at: 10_addressing_reporting_biases.htm.
de Denus S., Sanoski C.A., Carlsson J., and al. Rate vs rhythm control in patients with atrial fibrillation: a meta-analysis Arch Intern Med 2005 ;  165 : 258-262 [cross-ref]
Testa L., Biondi-Zoccai G.G., Dello Russo A., and al. Rate control vs. rhythm control in patients with atrial fibrillation: a meta-analysis Eur Heart J 2005 ;  26 : 2000-2006 [cross-ref]
Wattigney W.A., Mensah G.A., Croft J.B. Increased atrial fibrillation mortality: United States, 1980-1998 Am J Epidemiol 2002 ;  155 : 819-826 [cross-ref]
Held P.H., Yusuf S. Effects of beta-blockers and calcium-channel blockers in acute myocardial infarction Eur Heart J 1993 ;  14 Suppl. F : 18-25
Joglar J.A., Acusta A.P., Shusterman N.H., and al. Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program Am Heart J 2001 ;  142 : 498-501 [inter-ref]
Echt D.S., Liebson P.R., Mitchell L.B., and al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial N Engl J Med 1991 ;  324 : 781-788 [cross-ref]
Buxton A.E., Lee K.L., Fisher J.D., and al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter unsustained tachycardia trial investigators N Engl J Med 1999 ;  341 : 1882-1890 [cross-ref]
Kahn S.R., Solymoss S., Flegel K.M. Non-valvular atrial fibrillation: evidence for a prothrombotic state CMAJ 1997 ;  157 : 673-681
Ohara K., Inoue H., Nozawa T., and al. Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation Int J Cardiol 2008 ;  126 : 316-321 [cross-ref]
Lindh J.D., Holm L., Dahl M.L., and al. Incidence and predictors of severe bleeding during warfarin treatment J Thromb Thrombolysis 2008 ;  25 : 151-159 [cross-ref]
Hagens V.E., Vermeulen K.M., TenVergert E.M., and al. Rate control is more cost-effective than rhythm control for patients with persistent atrial fibrillation – results from the RAte Control versus Electrical cardioversion (RACE) study Eur Heart J 2004 ;  25 : 1542-1549 [cross-ref]
Marshall D.A., Levy A.R., Vidaillet H., and al. Cost-effectiveness of rhythm versus rate control in atrial fibrillation Ann Intern Med 2004 ;  141 : 653-661
Pietrasik A., Kosior D.A., Niewada M., and al. The cost comparison of rhythm and rate control strategies in persistent atrial fibrillation Int J Cardiol 2007 ;  118 : 21-27 [cross-ref]
Hart R.G., Pearce L.A., Miller V.T., and al. Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies Cerebrovasc Dis 2000 ;  10 : 39-43 [cross-ref]
Camm A.J., Kirchhof P., Lip G.Y., and 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 : 2369-2429
Fuster V., Ryden L.E., Cannom D.S., and 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 : e257-e354



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