Friday, August 31, 2007

Clinical Evidence Concise

This clinical content conforms to AAFP criteria for evidence-based continuing medical education

A Publication of BMJ Publishing Group

Atrial Fibrillation (Chronic)

christopher j. boos, Deidre a. lane, and Gregory y.h. lipUniversity Department of Medicine, City Hospital, Birmingham, United Kingdom

What are the effects of oral medical treatments to control heart rate in persons with chronic (longer than one week) nonvalvular atrial fibrillation?

likely to be beneficial

Beta Blockers vs. Digoxin (Beta Blockers More Effective Than Digoxin in Controlling Symptoms). One randomized controlled trial (RCT) identified by a systematic review found that digoxin reduced nocturnal heart rate compared with carvedilol in persons with chronic nonvalvular atrial fibrillation. It found no significant difference in 24-hour ventricular rate, exercise tolerance, or daytime and exercise heart rate. The systematic review, which also included weaker evidence from an RCT on a withdrawn drug and expert opinion, concluded that beta blockers should be used in preference to digoxin in persons who are not sedentary.

(Categorization based on consensus.)

Beta Blockers Plus Digoxin vs. Beta Blockers Alone (Beta Blockers Plus Digoxin More Effective Than Beta Blockers Alone). We found no systematic review or RCTs of persons with chronic nonvalvular atrial fibrillation that met BMJ Clinical Evidence inclusion criteria. A systematic review, which also included weaker evidence, an RCT on a withdrawn drug, and expert opinion supported the addition of digoxin when a beta blocker alone is ineffective. (Categorization based on consensus.)

Calcium Channel Blockers (Rate Limiting) vs. Digoxin (Calcium Channel Blockers More Effective Than Digoxin for Controlling Heart Rate). One RCT identified by a systematic review found that verapamil lowered rest and exercise heart rate more effectively than digoxin in persons with chronic nonvalvular atrial fibrillation; however, significance was not assessed. The RCT also did not assess harms. The systematic review, which also included weaker evidence and expert opinion, supported the use of rate-limiting calcium channel blockers over digoxin as initial monotherapy in most persons, with the exception of sedentary persons. (Categorization based on consensus.)

Calcium Channel Blocker (Rate Limiting) Plus Digoxin vs. Calcium Channel Blocker (Rate Limiting) Alone (Calcium Channel Blocker Plus Digoxin More Effective Than Calcium Channel Blocker Alone). One RCT identified by a systematic review found that calcium channel blockers plus digoxin decreased resting and exercise heart rate and improved maximal effort capacity compared with calcium channel blockers alone. The systematic review, which also included weaker evidence and expert opinion, supported the addition of digoxin when a calcium channel blocker alone was ineffective.

trade-off between benefits and harms

Beta Blockers vs. Rate-Limiting Calcium Channel Blockers (Selection Is Dependent on Individual Risk Factors and Coexisting Morbidities). One RCT identified by a systematic review found that, in persons taking digoxin, ventricular rates (during rest and exercise), average heart rate, and maximal heart rates were lower with a beta blocker compared with a calcium channel blocker. Minimal heart rate was similar in both groups. More adverse effects were reported with the beta blocker than with the calcium channel blocker. The systematic review, which also included weaker evidence and expert opinion, supported the use of beta blockers or calcium channel blockers.

What is the effect of different treatment strategies for persons with persistent nonvalvular atrial fibrillation?

trade-off between benefits and harms

Rhythm Control vs. Rate Control (Selection Dependent on Individual Risk Factors and Coexisting Morbidities). We found inconclusive results from RCTs comparing rhythm control versus rate control strategies. One systematic review found that rate control was associated with a better prognosis than rhythm control when the combined end point of all-cause mortality and thromboembolic events was examined, particularly in older persons. Another systematic review and one RCT found no significant difference between rhythm and rate control in thromboembolism, strokes, and major bleeding. RCTs found that rhythm control improved exercise tolerance, reduced ventricular heart rate, and achieved sinus rhythm compared with rate control; however, the difference did not reach significance in some RCTs. Two RCTs found no difference in quality of life between rhythm and rate control. Adverse effects were more common with rhythm control strategies compared with rate control strategies. Current consensus supports the use of either rhythm or rate control depending on individual risk factors and coexisting morbidities.


Atrial fibrillation is the most commonly encountered and sustained cardiac arrhythmia in clinical practice.1 It is a supraventricular tachyarrhythmia, which is characterized by the presence of uncoordinated atrial activation and deteriorating atrial mechanical function.1,2 On the surface electrocardiography, P waves are absent and are replaced by rapid fibrillatory waves that vary in size, shape, and timing, leading to an irregular ventricular response when atrioventricular conduction is intact.


Chronic atrial fibrillation is most commonly classified according to its temporal pattern.3 Faced with a first detected episode of atrial fibrillation, three recognized patterns of chronic disease may develop: (1) persistent atrial fibrillation describes an episode of sustained atrial fibrillation (usually longer than seven days) that does not convert to sinus rhythm without medical intervention, with the achievement of sinus rhythm by pharmacologic or electrical cardioversion; (2) paroxysmal atrial fibrillation refers to self-terminating episodes of atrial fibrillation, usually lasting less than 48 hours (paroxysmal and persistent atrial fibrillation may be recurrent); and (3) permanent atrial fibrillation, episodes of persistent atrial fibrillation (usually longer than one year), in which cardioversion is not attempted or is unsuccessful, with atrial fibrillation accepted as the long-term rhythm for that person. Lone atrial fibrillation is largely a diagnosis of exclusion and refers to atrial fibrillation occurring in the absence of concomitant cardiovascular disease (e.g., hypertension) or structural heart disease (normal echocardiography), with normal electrocardiography and chest radiography.2

In most cases of suspected atrial fibrillation, 12-lead electrocardiography is sufficient for diagnosis confirmation.2 Where diagnostic uncertainty remains, such as in chronic permanent atrial fibrillation, the use of 24-hour (or even seven-day) Holter monitoring or event recorder (e.g., Cardiomemo) may also be required.2 The most common presenting symptoms of chronic atrial fibrillation are palpitations, shortness of breath, fatigue, chest pain, dizziness, and stroke.1,2

Incidence and Prevalence

Atrial fibrillation carries an overall population prevalence of 0.5 to 1.0 percent and an incidence of 0.54 cases per 1,000 person-years.4,5 The prevalence of atrial fibrillation is highly age dependent and increases markedly with each advancing decade of age, from 0.5 percent at 50 to 59 years of age to almost 9 percent at 80 to 90 years of age.6 The incidence of atrial fibrillation has a male predisposition, affecting men 1.5 times more commonly than women.7 The Screening for Atrial Fibrillation in the Elderly project reported that the baseline prevalence of atrial fibrillation in persons older than 65 years was 7.2 percent, with a higher prevalence in men (7.8 percent) and persons at least 75 years of age, with an incidence of 0.69 to 1.64 percent a year, depending on screening method.8 These incidence data refer to cross-sectional study data whereby most persons would have atrial fibrillation of more than seven days duration (persistent, paroxysmal, or permanent atrial fibrillation), and not acute atrial fibrillation.


Atrial fibrillation is linked to all types of cardiac disease, including cardiothoracic surgery, as well as to a large number of noncardiac conditions such as thyroid disease, any pyrexial illness, electrolyte imbalance, cancer, and acute infections.1,2


Chronic atrial fibrillation confers an enormous and significant clinical burden. It is an independent predictor of mortality and is associated with an odds ratio for death of 1.5 for men and 1.9 for women, independent of other risk factors.9 It increases the risk of ischemic stroke and thromboembolism by an average of fivefold.10 Furthermore, the presence of chronic atrial fibrillation is linked to far more severe strokes, with greater disability and lower discharge rate to their own home.10,11 Chronic atrial fibrillation is common (3 to 6 percent of all medical admissions)2 and results in longer hospital stays. In addition, chronic atrial fibrillation increases the development of heart failure and adversely affects quality of life, including cognitive function.12

search date: June 2006
Adapted with permission from Boos CJ, Lane DA, Lip GY. Atrial fibrillation (chronic). Clin Evid Handbook June 2007:27-9.

Author disclosure: Nothing to disclose.

1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257-e354.
2. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London, UK: Royal College of Physicians, 2006. Accessed June 15, 2007, at:
3. Levy S, Camm AJ, Saksena S, et al. International consensus on nomenclature and classification of atrial fibrillation; a collaborative project of the Working Group on Arrhythmias and the Working Group on Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Europace 2003;5:119-22.
4. Stewart S, Hart CL, Hole DJ, et al. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001;86:516-21.
5. Murdoch DL, O'Neill K, Jackson J, et al. Are atrial fibrillation guidelines altering management? A community based study. Scott Med J 2005;50:166-9.
6. Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998;82:2N-9N.
7. Singh SN, Tang XC, Singh BN, et al. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy. J Am Coll Cardiol 2006;48:721-30.
8. Hobbs FD, Fitzmaurice DA, Mant J, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess 2005;9:1-74.
9. Benjamin EJ, Wolf PA, D'Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946-52.
10. Wolf PA, D'Agostino RB, Belanger AJ, et al. Probability of stroke: a risk profile from Framingham Study. Stroke 1991;22:312-8.
11. Jorgensen HS, Nakayama H, Reith J, et al. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996;27:1765-9.
12. Freestone B, Lip GYH. Epidemiology and costs of cardiac arrhythmias. In: Lip GYH, Godtfredson J, eds. Cardiac Arrhythmias: A Clinical Approach. Edinburgh, UK: Mosby, 2003:3-24.

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