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Atrial Fibrillation

This guidance is for the management of patients with atrial fibrillation, including patients with paroxysmal atrial fibrillation. It includes advice on control of ventricular rate, indications for cardioversion, and need for antithrombotic treatment. It does not advise on the management of childhood cases.

Goals and outcomes

Goals

bulletTo establish the diagnosis
bulletTo control ventricular rate
bulletTo identify those patients suitable for attempted cardioversion
bulletTo identify those patients suitable for antithrombotic medication to reduce the risk of stroke

Outcome measures

bulletProportion of patients with resting ventricular rate less than 90/minute.
bulletProportion of patients on warfarin, where this is indicated and there are no contraindications
bulletMaintained sinus rhythm in patients who have been successfully cardioverted.

 

Background information

CONTENT
bulletWhat is it?
bulletHow common is it?
bulletHow do I know my patient has it?
bulletWhat else might it be?
bulletRisk of stroke?
bulletWhat can go wrong?

 

What is it ?

bulletAtrial fibrillation (AF) is an arrhythmia in which electrical activity in the atria is disorganised. The atrio-ventricular (AV) node receives more electrical impulses than it can conduct, and most of these impulses are blocked resulting in an irregular ventricular rhythm. The ventricular rate can vary between 50-200 per minute, depending on the degree of AV conduction.
bulletAF is most commonly associated with hypertensive and ischaemic heart disease, heart failure, cardiomyopathy, mitral valve disease, alcohol excess, pulmonary embolism, and hyperthyroidism. It may also occur with acute systemic infection, hypoxia, and post cardiac surgery. Rheumatic heart disease is now an uncommon cause in developed countries [DTB, 1996].
bulletUp to a third of patients have "lone AF", i.e. a structurally normal heart and no significant co-morbid disease [Lip and Lowe, 1996].

How common is it ?

bulletPrevalence of atrial fibrillation (AF) increases with age. Prevalence in the general population aged 65 years and older is 4.7% (95% CI 4.1% to 5.3%). In those aged 65 to 74 years, prevalence in men is 3.5% (2.4-4.7) and in women it is 2.4% (1.4-3.5). Among those aged 75 years and older the prevalence in men is 10% (8.3-11.7) and in women is 5.6% (4.4-6.8) [Sudlow et al. 1998b].
bulletAF is found in 15% of all stroke patients and in 2-8% of transient ischaemic attack patients [Royal College of Physicians of Edinburgh, 1999].

How do I know my patient has it ?

bulletThe patient may be asymptomatic or may complain of palpitations, chest pain, breathlessness or giddiness.
bulletThe pulse is irregular and can range between 50-200 beats per minute.
bulletThe diagnosis is confirmed by electrocardiography, which shows no P waves, a chaotic baseline and an irregular ventricular rate. The ventricular complexes look normal unless there is a ventricular conduction defect.

What else might it be ?

An irregular pulse may be due to multiple atrial or ventricular ectopic beats, or variable atrio-ventricular block.

Risk of stroke?

bulletThe risk of stroke in patients with atrial fibrillation (AF) and rheumatic mitral stenosis is markedly increased.
bulletEven in the absence of rheumatic heart disease several studies have identified AF as an important risk factor for stroke [Reid et al. 1974; Rose et al. 1978; Wolf et al. 1991]. The overall incidence of stroke in chronic non-valvular AF (NVAF) is 5% per year [AFI, 1994].
bulletThe relative risk of paroxysmal versus chronic NVAF is uncertain but is probably the same [Laupacis and Cuddy, 1995; SIGN, 1999].
bulletThrombotic risk is increased with age, hypertension, heart failure, diabetes, and a history of a previous embolic event [AFI, 1994; Laupacis and Cuddy, 1995; SIGN, 1999].
bulletPatients less than 65 years of age who do not have any of these risk factors have a low risk of stroke.
bulletPatients greater than 65 years of age, or younger patients with any of these risk factors, have an annual stroke risk greater than 3-4%.
bulletUp to 20% of those with AF who have a first stroke will have a further episode within a year.

What can go wrong ?

bulletThe loss of synchronised atrial contractions and the irregular and often rapid ventricular rate can impair cardiac performance, leading to myocardial ischaemia, hypotension, heart failure and tachycardia-induced cardiomyopathy. Patients with pre-existing cardiac disease are particularly vulnerable.
bulletAtrial fibrillation (AF) increases the risk of thrombotic stroke (see previous).
bulletThe mortality rate with AF is twice that of the general population [Laupacis and Cuddy, 1995].

 

Management issues

 

CONTENT
bulletDiagnosis and investigation
bulletRate control
bulletRhythm control
bulletCardioversion
bulletParoxysmal atrial fibrillation
bulletAntithrombotic treatment

Diagnosis and investigation

bulletScreening by detection of an irregular pulse misses few cases of atrial fibrillation (AF), but only 8-23% of patients are subsequently found to have AF on electrocardiograph (ECG) [Sudlow et al. 1998a].
bulletAlways confirm the presence of AF by ECG, i.e. no P waves, a baseline that appears to be irregular and undulating, and an irregular ventricular rate. The ventricular complexes look normal unless there is a ventricular conduction defect.
bulletAn ECG may also indicate a possible underlying cause, e.g. signs of ischaemia, an old myocardial infarction, left ventricular hypertrophy, or a pre-excitation syndrome (e.g. delta wave in the Wolff-Parkinson-White syndrome if in sinus rhythm).
bulletArrange baseline blood tests - full blood count to identify anaemia, serum electrolytes in case digoxin needed and to identify impaired renal function, thyroid function tests to identify thyrotoxicosis [Gillis et al. 1995]. If anticoagulation is planned additional investigations are coagulation screen and liver function tests [British Society for Haematology, 1998; SIGN, 1999].
bulletConsider a chest X-ray. In a young patient it may suggest the presence of congenital heart disease, such as atrial septal defect. In an older patient it can give information on the size of the heart and whether heart failure is present [Lip et al. 1995].
bulletThe routine use of echocardiography continues to be debated. It may provide useful information on the presence of associated valvular disease and ventricular failure, and a recent consensus statement recommends that it should be part of the optimal assessment of patients with AF [Royal College of Physicians of Edinburgh, 1999]. However, for the majority of patients it is unlikely to affect the decision on whether to recommend anticoagulation or not [Sudlow et al. 1998b; Cantley et al. 2000].
bulletAmbulatory ECG monitoring, event recorders, and exercise tolerance testing may be of value in selected patients [Gillis et al. 1995].

Rate control

bulletInappropriate ventricular rate is one of the main causes of symptoms in patients with atrial fibrillation. Although there is a lack of good quality data from trials of drug treatment, recent studies of atrio-ventricular node ablation and pacing show significant improvements in symptoms and exercise tolerance [Royal College of Physicians of Edinburgh, 1999].
bulletThe goal of treatment is usually to keep the ventricular rate less than 90/minute at rest and 180/minute on exercise [Rawles, 1990; Royal College of Physicians of Edinburgh, 1999].
bulletDigoxin alone may control the ventricular rate in a resting patient but is less effective at controlling heart rate during exercise [Royal College of Physicians of Edinburgh, 1999; Segal et al. 2000b].
bulletBeta-blockers or rate limiting calcium-channel blockers (verapamil or diltiazem) are as effective as digoxin at controlling resting heart rate and are more effective at controlling heart rate on exercise [Segal et al. 2000b]. They should therefore be considered for first line use, particularly in patients with hypertension or angina [Royal College of Physicians of Edinburgh, 1999].
bulletIf rate control is not achieved despite adequate monotherapy, then consider combining digoxin with a beta-blocker or verapamil, or consider referral. Diltiazem is not currently licensed for treatment of arrhythmias, and it is difficult to recommend dosing as trials have been small and dosing has varied enormously. Verapamil must not be combined with a beta-blocker due to the risk of bradycardia and reduced cardiac output.
bulletCombination of digoxin with a beta-blocker or verapamil may be particularly useful in exercise-induced tachycardia and may avoid the need for higher doses of either medication [Beasley et al. 1985; Gardner and Gilbert, 1995; DTB, 1996; Royal College of Physicians of Edinburgh, 1999; Segal et al. 2000b].
bulletIn refractory cases, amiodarone may be effective when other drugs have failed. However, this has a high incidence of side effects and should only be initiated under specialist supervision.
bulletRadio-frequency ablation of the atrio-ventricular node and pacemaker implantation should be considered in patients in whom medical treatment is ineffective or not tolerated [Gardner and Gilbert, 1995; Klein and Kerr, 1995; Royal College of Physicians of Edinburgh, 1999]. There are currently no large randomised controlled trials comparing AV node ablation and pacing against medical management.

Rhythm control

bulletRestoration and maintenance of sinus rhythm improves exercise tolerance and cardiac output in patients with atrial fibrillation [Royal College of Physicians of Edinburgh, 1999]. It is not known, however, whether this is more effective than rate control at reducing symptoms, or improving survival and reducing the risk of thromboembolism. Results from a small, unblinded pilot study suggest that rhythm control may be more effective at improving exercise tolerance, but with no effect on quality of life and at the cost of increased drug side effects and more frequent hospital admissions [Hohnloser et al. 2000]. The results from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, due to finish late 2001, will hopefully clarify these issues [Wyse, 2000].

Cardioversion

bulletThis is a secondary care intervention.
bulletCardioversion is most likely to be successful and maintained when the duration of atrial fibrillation (AF) is short [Royal College of Physicians of Edinburgh, 1999; Houghton et al. 2000].
bulletCardioversion is associated with an increased risk of thromboembolism in patients who have been in AF for more than 2 days; such patients should be treated with warfarin for 3 weeks prior to cardioversion and for at least 4 weeks following this [British Society for Haematology, 1998; Laupacis et al. 1998; SIGN, 1999].
bulletElectrical cardioversion by synchronised direct current shock is currently the preferred method and has a success rate of more than 90% in selected cases [Talajic et al. 1995; Lip et al. 1996; Royal College of Physicians of Edinburgh, 1999]. There have been no randomised controlled trials of electrical cardioversion.
bulletPharmacological cardioversion can be attempted with either the Class I agents quinidine, disopyramide, flecainide and propafenone, or the Class III agent amiodarone and possibly sotalol [Talajic et al. 1995; DTB, 1996]. The quality of clinical trials is generally poor, but evidence best supports the use of flecainide, with cardioversion rates of 60-90% [Royal College of Physicians of Edinburgh, 1999]. Digoxin, beta-blockers and verapamil have no effect on helping to restore sinus rhythm [Talajic et al. 1995; Royal College of Physicians of Edinburgh, 1999].
bulletRelapse rate following successful cardioversion is high: 60-75% of patients relapse, often in the first month [Talajic et al. 1995; DTB, 1996].
bulletThe use of anti-arrhythmic drugs after cardioversion in an attempt to maintain sinus rhythm is controversial and is not without risk. A recent large, but unblinded, randomised controlled trial found that over a 16 month period 35% of patients taking amiodarone had a recurrence of AF compared to 63% of patients taking sotalol or propafenone [Roy et al. 2000].

Indications for attempted cardioversion

bulletRecent onset atrial fibrillation (AF) - however, it is not always easy to know time of onset and there is a case for referring all patients with newly diagnosed AF for at least one attempt at cardioversion [DTB, 1996].
bulletNo structural heart disease, such as mitral valve disease, poor left ventricular function, or dilated left atrium.
bulletSuccessful treatment of any precipitating cause of atrial fibrillation (e.g. thyrotoxicosis, chest infection.
bulletYoung age, although age should not be an automatic barrier.
bulletPatients with acute AF and severe hypotension, acute heart failure, or unstable angina, who do not respond promptly to medical management [Gardner and Gilbert, 1995; Talajic et al. 1995].

Paroxysmal atrial fibrillation

bulletParoxysmal atrial fibrillation (PAF) is defined as intermittent episodes of AF with sinus rhythm in between - there is no accepted threshold for the time in between episodes.
bulletPsychological morbidity may be significant. Many patients avoid activities for fear of precipitating an episode. Patients may believe that their "heart will stop" or they will have a "heart attack" and such fears should be addressed [Royal College of Physicians of Edinburgh, 1999].
bulletThe risk of thromboembolism is probably the same as that for chronic AF and the same criteria for antithrombotic treatment apply.
bulletAnti-arrhythmic treatment aims to reduce the frequency and severity of attacks, and possibly prevent progression to persistent AF [DTB, 1996; Royal College of Physicians of Edinburgh, 1999].
bulletTreatment may not be necessary if symptomatic episodes are mild, infrequent, and short lasting. The benefits of treatment have to be balanced against the risks of long-term anti-arrhythmic medication.
bulletAnti-arrhythmic treatment should be initiated only under specialist supervision.
bulletA large number of drugs have been shown to reduce the frequency of episodes. Flecainide, propafenone, and sotalol have been most studied and are generally well tolerated. Disopyramide and quinidine are effective but are more likely to cause side effects [Royal College of Physicians of Edinburgh, 1999]. Recent trial data suggest that amiodarone may be particularly effective [Roy et al. 2000].
bulletCo-administration of atrio-ventricular blocking drugs (verapamil, diltiazem, and beta-blockers) with anti-arrhythmic drugs may reduce symptoms during attacks and may reduce the risk of dangerous one-to-one conduction of atrial flutter [Royal College of Physicians of Edinburgh, 1999].
bulletDigoxin is not generally recommended as it does not reduce the frequency of paroxysms and may worsen rate control during paroxysms [Rawles et al. 1990; Galun et al. 1991; Gardner and Gilbert, 1995; Royal College of Physicians of Edinburgh, 1999].

Antithrombotic treatment

bulletPatients with mitral valve disease and atrial fibrillation (AF) have a markedly increased risk of embolic stroke. Despite the few randomised controlled trials carried out it is accepted such patients should be treated with warfarin.
bulletAF is an important risk factor for stroke even in the absence of mitral valve disease, i.e. non-valvular AF (NVAF) [Reid et al. 1974; Rose et al. 1978; Wolf et al. 1991]. There have now been several randomised controlled trials examining the use of anticoagulant and antiplatelet therapy in NVAF, with significant benefit shown.

Primary prevention

bulletWarfarin: Meta-analysis of five primary prevention studies [AFASAK, 1989; BAATAF, 1990; CAFA, 1991; SPAF-I, 1991; VA-SPINAF, 1992] showed that warfarin reduced the incidence of stroke by 68% (95% CI 50% to 79%), with an absolute annual risk reduction of 3.1% [AFI, 1994]. Recent meta-analyses come to virtually identical conclusions [Segal et al. 2000a; Benavente et al. 2000b].
bulletFor AF patients with an annual risk of stroke of 4% per year, about 25 strokes (of which 12 would have been disabling or fatal) will be prevented yearly for every 1000 given warfarin.
bulletAspirin: 2 primary prevention studies compared aspirin with placebo [AFASAK, 1989; SPAF-I, 1991]. The AFASAK trial, using 75 mg aspirin per day, showed a non-significant 18% reduction in stroke rate. The SPAF-I study, using 325 mg of aspirin per day, showed a significant reduction in stroke rate of 44% (95% CI 7% to 66%). Recent meta-analyses, using pooled data from these two trials, show a non-significant reduction in the incidence of stroke of 30-44%, with 95% confidence intervals ranging from -35% to +81% [Segal et al. 2000a; Benavente et al. 2000a].

Secondary prevention

bulletThe secondary prevention EAFT study assigned patients with a recent history of transient ischaemic attack or minor stroke to warfarin, aspirin 300 mg, or placebo [EAFT, 1993].
bulletWarfarin reduced the incidence of stroke by 66% (95% CI 43% to 80%), an absolute risk reduction of 8%.
bulletAspirin reduced the incidence of stroke by 14%, but this was not statistically significant.
bulletFor AF patients with a history of TIA or stroke, 90 vascular events (mainly strokes) will be prevented yearly for every 1000 given warfarin [Koudstaal, 2000a].

Warfarin versus aspirin

bulletWarfarin is superior to aspirin for stroke prevention in patients with atrial fibrillation (AF); warfarin reduces the risk of stroke by nearly two-thirds, while aspirin reduces the risk by about one-fifth.
bulletA recent Cochrane systematic review combined data from all placebo-controlled randomised trials of aspirin and AF and found that aspirin significantly reduced the risk of stroke by about 20% [Benavente et al. 2000a].
bulletThe SPAF-II study directly compared aspirin against warfarin [SPAF-II, 1994]. Aspirin was as effective as warfarin in preventing total or disabling strokes, although warfarin was more effective in preventing ischaemic strokes.
bulletThe SPAF-III study randomised high-risk elderly patients with AF to receive either adjusted-dose warfarin to achieve a target INR of 2.0-3.0, or the combination of fixed-dose warfarin to achieve an INR of 1.2-1.5 plus 325 mg of aspirin [SPAF-III, 1996]. The study had to be discontinued early due to an increased incidence of primary events (ischaemic stroke and systemic embolism) in patients given combination therapy compared to adjusted dose warfarin. The absolute rate difference was 6% per year (95% CI 3.4% to 8.6%), equating to a relative risk reduction of 74% (95% CI 50% to 87%).
bulletIn the secondary prevention EAFT study, warfarin compared to aspirin reduced the risk of stroke by two thirds [EAFT, 1993]. An extra 60 strokes were prevented for every 1000 patients treated with warfarin instead of aspirin [Koudstaal, 2000b].

Risk of bleeding complications on oral anticoagulants

bulletThe annual rate of proven cerebral haemorrhage and other bleeding complications has been low in all the trials. It is not known whether such low bleeding risks can be routinely achieved in normal clinical practice. However, data from a large prospective community cohort study show that similar low rates are achievable [Palareti et al. 1996].
bulletIn the primary prevention studies, major haemorrhage occurred in 1.3% of warfarin-treated patients and 1.0% of controls [AFI, 1994]. The corresponding rates for intracranial haemorrhage were 0.3% and 0.1%.
bulletThe risk of bleeding is considerably lower with aspirin. However, there is still a small absolute increase in risk of intracranial haemorrhage of 12 events per 10,000 persons treated with aspirin [He et al. 1998].
bulletRisk of bleeding is greatest during the first 3 months of anticoagulation and increases with age, intensity of anticoagulation, prior gastrointestinal bleed, prior stroke and severe co-morbid disease [Sweeney et al. 1995; Connolly and Turpie, 1995; Palareti et al. 1996].
bulletSuggested contra-indications and cautions (adapted from SIGN 1999):

 

Contraindications/cautions Comments
Uncorrected major bleeding  
Uncorrected major bleeding disorder e.g. thrombocytopenia, haemophilias, liver failure, renal failure
Uncontrolled severe hypertension e.g. systolic greater than 200 mm Hg or diastolic greater than 120 mm Hg
Potential bleeding lesions e.g. active peptic ulcer
oesophageal varices
aneurysm
proliferative retinopathy
recent organ biopsy
recent trauma or surgery to head, orbit, spine
recent stroke
confirmed intracranial or intraspinal bleed
Pregnancy risk of teratogenicity
Uncooperative/unreliable patient concordance and follow up issues
Repeated falls or unstable gait increased chance of injury and head trauma
Concomitant use of NSAIDs increased risk of gastrointestinal bleeding
Protein C deficiency risk of skin necrosis on initiation of treatment, so caution needed

 

Who to treat with oral anticoagulation?

bulletRecent evidence based guidelines recommend that patients with an annual risk of stroke greater than 3% should be considered for warfarin [SIGN, 1999]. At this level of risk the benefits of anticoagulation outweigh potential harm [Gage et al. 1995; Glasziou and Irwig, 1995].
bulletThe table below highlights those patients who are likely to be at significantly increased risk of stroke and the degree of benefit from treatment with either warfarin or aspirin [SIGN, 1999]. The numbers needed to treat with warfarin instead of aspirin for 1 year to prevent one stroke are also shown:
Risk group Untreated Aspirin Warfarin NNT
Very high

Previous ischaemic stroke or TIA

12%

10%

5%

13
High

Age over 65 and one other risk factor

- hypertension
- diabetes
- heart failure
- left ventricular dysfunction

5-8%

4-6%

2-3%

22-47
Moderate

- Age over 65, no other risk factors

- Age under 65, other risk factors

3-5%

2-4%

1-2%

47-83
Low

Age under 65, no other risk factors

1.2%

1%

0.5%

200
bulletRisk stratification tables with recommendations for treatment have also been produced by a group using decision analysis methods [Thomson et al. 2000].
bulletPatient attitudes to anticoagulation strongly influence the cost/benefit of treatment and should always be taken into account [Caro et al. 1993; Man-Son-Hing et al. 1999; Thomson et al. 2000; Protheroe et al. 2000].
bulletIf an acute cerebral ischaemic event has occurred, anticoagulant treatment should be delayed until most of the deficit has resolved or, in the case of more severe strokes, more than 2 weeks has elapsed [SIGN, 1999].

Level of anticoagulation

bulletThe consensus is to aim for a target INR of 2.5 (range 2.0-3.0) [Hylek et al. 1996; British Society for Haematology, 1998; Laupacis et al. 1998; Royal College of Physicians of Edinburgh, 1999; SIGN, 1999].
bulletFor patients older than 75 years, it may be safer to aim for a target INR at the lower end of this range, due to their increased risk of cerebral haemorrhage [Royal College of Physicians of Edinburgh, 1999]. Alternatively, aspirin may be a safer option in some patients.
bulletThe risk of bleeding increases considerably above an INR of 4 [Palareti et al. 1996].

Who to treat with aspirin

bulletAspirin should be considered for patients who fulfil the criteria for anticoagulation but where warfarin is contra-indicated or declined. It may also be more suitable for patients who are likely to have difficulty following dosing instructions for warfarin.
bulletTreatment is not usually recommended for patients with "lone AF" under age 65, unless aspirin is given for other indications [SIGN, 1999].

Dose of Aspirin

bulletRecommended doses range between 75mg and 300 mg daily [Eccles et al. 1998; Royal College of Physicians of Edinburgh, 1999; SIGN, 1999].
bulletLocal guidelines on aspirin dosage should be followed where available. Otherwise we recommend a dose of 75 mg daily.

Applicability to primary care

bulletAll the major studies looking at antithrombotic treatment in atrial fibrillation (AF) were based in secondary care, and caution is needed in interpreting the data for primary care patients.
bulletA recent primary care based study found that in low risk patients with AF aspirin was as effective as warfarin in preventing stroke [Hellemons et al. 1999]. This is consistent with the recommendations within this guidance. Other conclusions from this study are limited due to methodological problems, in particular small sample size, and further primary care based studies are needed.

Other antiplatelet agents

bulletThe role of other antiplatelet agents is uncertain at the present time. A Cochrane systematic review addressing this issue is due to be published within the next year [Segal, 2000].

 

References

 

Cited
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  40. Rose, G., Baxter, P.J., Reid, D.D. and McCartney, P. (1978) Prevalence and prognosis of electrocardiographic findings in middle-aged men. British Heart Journal 40, 636-643.
  41. Roy, D., Talajic, M., Dorian, P., et al (2000) Amiodarone to prevent recurrence of atrial fibrillation. New England Journal of Medicine 342, 913-920.
  42. Royal College of Physicians of Edinburgh (1999) The Sir James MacKenzie Consensus Conference: atrial fibrillation in hospital and general practice. Proceedings of the Royal College of Physicians of Edinburgh 29,
  43. Segal, J. (2000) Anticoagulants versus antiplatelet drugs for preventing thromboembolism in atrial fibrillation (Protocol for a Cochrane Review)). The Cochrane Library (Issue 4). Update Software.
  44. Segal, J.B., McNamara, R.L., Miller, M.R., et al (2000a) Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs. Journal of General Internal Medicine 15, 56-67.
  45. Segal, J.B., McNamara, R.L., Miller, M.R., et al (2000b) The evidence regarding the drugs used for ventricular rate control. Journal of Family Practice 49, 47-49.
  46. SIGN (1999) Atrial fibrillation: prophylaxis of systemic embolism. Scottish Intercollegiate Guidelines Network. pp.18-22.
  47. SPAF-I (1991) Stroke prevention in atrial fibrillation study. Circulation 84, 527-539.
  48. SPAF-II (1994) Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: stroke prevention in atrial fibrillation II study. Lancet 343, 687-691.
  49. SPAF-III (1996) Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 348, 633-638.
  50. Sudlow, M., Rodgers, H., Kenny, R.A. and Thomson, R. (1998a) Identification of patients with atrial fibrillation in general practice: a study of screening methods. British Medical Journal 317, 327-328.
  51. Sudlow, M., Thomson, R., Thwaites, B., et al (1998b) Prevalence of atrial fibrillation and eligibility for anticoagulants in the community. Lancet 352, 1167-1171.
  52. Sweeney, K.G., Gray, D.P., Steele, R. and Evans, P. (1995) Use of warfarin in non-rheumatic atrial fibrillation: a commentary from general practice. British Journal of General Practice 45, 153-158.
  53. Talajic, M., MacDonald, R., and Nattel, S. (1995) Restoration of sinus rhythm in patients with atrial fibrillation. Clinical Practice Guideline. Canadian Medical Association. http://www.ccs.ca/consensus/reports/atrial3/mario/index.html
  54. 54. Thomson, R., Parkin, D., Eccles, M., et al (2000) Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet 355, 956-962.
  55. VA-SPINAF (1992) Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation: Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. New England Journal of Medicine 327, 1406-1412.
  56. Wolf, P.A., Abbott, R.D. and Kannel, W.B. (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22, 983-988.
  57. Wyse, D.G. (2000) The AFFIRM Trial: main trial and substudies - what can we expect? Journal of Interventional Cardiac Electrophysiology 4, 171-176.

Background reading

  1. Bennet, D.H. (1997) Cardiac Arrythmias: practical notes on interpretation and treatment, 5th edn.
  2. Berge, E., Abdelnoor, M., Nakstad, P.H. and Sandset, P.M. (2000) Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. Lancet 355, 1205-1210.
  3. Connolly, S.J. (2000) Anticoagulation for patients with atrial fibrillation and risk factors for stroke: warfarin reduces the risk by two thirds, but doctors still aren't prescribing it enough. British Medical Journal 320, 1219-1220.
  4. Conover, M.B. (1996) Understanding electrocardiography, 7th edn. St Louis: Mosby.
  5. Cotter, G., Blatt, A., Kaluski, E., et al (1999) Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study. European Heart Journal 20, 1833-1842.
  6. EBM (2000) Review: antithrombotic agents prevent stroke in non-valvular atrial fibrillation. Evidence Based Medicine 5, 82
  7. Ezekowitz, M.D. and Levine, J.A. (1999) Preventing stroke in patients with atrial fibrillation. Journal of the American Medical Association 281, 1830-1835.
  8. Fornaro, G., Rossi, P., Mantica, P.G., et al (1993) Indobufen in the prevention of thromboembolic complications in patients with heart disease. A randomized, placebo-controlled, double-blind study. Circulation 87, 162-164.
  9. Gallus, A.S., Baker, R.I., Chong, B.H., et al (2000) Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis. Medical Journal of Australia 172, 600-605.
  10. Go, A.S., Hylek, E.M., Phillips, K.A., et al (2000) Implications of stroke risk criteria on the anticoagulation decision in nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrilation (ATRIA) study. Circulation 102, 11-13.
  11. Golzari, H., Cebul, R.D. and Bahler, R.C. (1996) Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy. Annals of Internal Medicine 125, 311-323.
  12. Hart, R.G., Benavente, O., McBride, R. and Pearce, L.A. (1999) Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Annals of Internal Medicine 131, 492-501.
  13. Hobbs, R. (1999) Identification and treatment of patients with atrial fibrillation in primary care. Heart 81, 333-334.
  14. Lightowlers, S. and McGuire, A. (1998) Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke. Stroke 29, 1827-1832.
  15. Lip, G.Y., Metcalfe, M.J. and Rae, A.P. (1993) Management of paroxysmal atrial fibrillation. Quarterly Journal of Medicine 86, 467-472.
  16. Lowe, G.D.O. (1994) Use of anticoagulants in atrial fibrillation. Prescribers' Journal 34, 91-101.
  17. Matchar, D.B., McCrory, D.C., Barnett, H.J.M. and Feussner, J.R. (1994) Medical treatment for stroke prevention [published erratum appears in Ann Intern Med 1994 Sep 15;121(6):470 and 1995 Jun 1;122(11):885]. Annals of Internal Medicine 121, 41-53.
  18. Middlekauff, H.R., Stevenson, W.G. and Gornbein, J.A. (2000) Antiarrhythmic prophylaxis vs warfarin anticoagulation to prevent thromboembolic events among patients with atrial fibrillation: a decision analysis. Archives of Internal Medicine 155, 913-920.
  19. Morley, J., Marinchak, R., Rials, S.J. and Kowey, P. (1996) Atrial fibrillation, anticoagulation, and stroke. American Journal of Cardiology 77, 38A-44A.
  20. Morocutti, C., Amabile, G., Fattapposta, F., et al (1997) Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators. Stroke 28, 1015-1021.
  21. Prystowsky, E.N., Benson, D.W.J., Fuster, V., et al (1996) Management of patients with atrial fibrillation. A Statement for Healthcare Professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation 93, 1262-1277.
  22. Somerville, S., Somerville, J., Croft, P. and Lewis, M. (2000) Atrial fibrillation: a comparison of methods to identify cases in general practice. British Journal of General Practice 50, 727-729.
  23. Stevenson, W.G. and Stevenson, L.W. (1999) Atrial Fibrillation in heart failure. New England Journal of Medicine 341,
  24. Sudlow, C. and Baigent, C. (2000) Stroke prevention. Clinical Evidence 3, 118-134.
  25. Sudlow, M., Thomson, R., Kenny, R.A. and Rodgers, H. (1998) A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. British Journal of General Practice 48, 1775-1778.
  26. Sudlow, M., Thomson, R., Kenny, R.A. and Rodgers, H. (1998) A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. British Journal of General Practice 48, 1775-1778.
  27. Thomson, R., McElroy, H. and Sudlow, M. (1998) Guidelines on anticoagulant treatment in atrial fibrillation in Great Britain: Variation in content and implications for treatment. British Medical Journal 316, 509-513.

 

Which scenario?

 

Rate control = Advice and prescriptions for the rate control of AF using digoxin, beta-blockers or rate limiting calcium-channel blockers.

Mx of paroxysmal AF = Advice on the management of paroxysmal atrial fibrillation. No prescriptions are offered.

Deciding antithrombotic Rx = Advice and prescriptions for antithrombotic treatment in patients with atrial fibrillation.

 

Scenario: Rate control

 

 

Which therapy?

 

REMEMBER TO CONSIDER THE NEED FOR WARFARIN OR ASPIRIN (SEE RELEVANT SCENARIO) OR REFERRAL FOR ATTEMPTED CARDIOVERSION (SEE REFERRAL ADVICE)
bulletConfirm the diagnosis by ECG.
bulletTreat any precipitating cause, e.g. thyrotoxicosis, chest infection.
bulletAim for a ventricular rate of less than 90/minute at rest and 180/minute on exercise.
bulletDigoxin is the preferred choice if the patient has co-existing heart failure. It is less effective, however, than other agents at controlling heart rate during exercise.
bulletA beta-blocker or verapamil should therefore be considered for first line use, particularly if co-existing hypertension or angina.
bulletIf despite adequate monotherapy rate control is not achieved, then consider combining digoxin with a beta-blocker or verapamil, or consider referral.

Notes on digoxin

bulletA loading dose of 500 micrograms daily for 3 days is suggested.
bulletLower loading and maintenance doses may be needed in the elderly or if renal impairment.
bulletThe maintenance dose usually ranges between 125-250 micrograms daily. The slowing of the ventricular rate is usually a good guide to the therapeutic effect.
bulletNomograms are an alternative way of deciding on the dose [Jelliffe and Brooker, 1974].

Notes on beta-blockers and verapamil

bulletUse standard doses, as recommended in the BNF, and increase according to response.

Clinically relevant side effects and cautions

Digoxin

bulletDigoxin has a narrow therapeutic window. The usual therapeutic plasma concentration ranges between 1-2 ng/ml.
bulletToxicity may be precipitated by metabolic disturbances (e.g. hypokalaemia, hypercalcaemia, hypoxia and acidosis, renal impairment, dehydration, and hypothyroidism) or by drugs that increase plasma levels (e.g. verapamil, amiodarone, and quinidine).
bulletIf verapamil is added to digoxin, the dose of digoxin should be reduced by 30-50% and then adjusted according to blood levels. Maximal effect on digoxin levels occurs within 14 days.
bulletSuspect toxicity if anorexia, nausea, vomiting, diarrhoea, mental confusion, or blurred vision.
bulletToxicity may cause a variety of arrhythmias, and apparent return of sinus rhythm may be due to digoxin toxicity (e.g. atrial tachycardia with AV block, junctional tachycardia, or atrial fibrillation with complete AV block). At toxic doses, digoxin may cause or worsen heart failure.
bulletDigoxin levels do not need to be routinely monitored since ventricular rate is usually a good guide to therapeutic effect. Monitoring levels may be of benefit to assess for possible toxicity, to check on adherence to treatment, or while adjusting the dose. Plasma levels must be measured at least 6 hours after the last dose.
bulletLevels less than 1.5 micrograms/litre, in the absence of hypokalaemia, indicate that digoxin toxicity is unlikely.
bulletLevels greater than 3.0 micrograms/litre indicate that toxicity is likely.
bulletWith levels between 1.5 and 3.0 micrograms/litre digoxin toxicity should be considered a possibility.
bulletAvoid in Wolff-Parkinson-White syndrome, as may cause the ventricular rate to accelerate.

Beta-blockers

bulletAvoid if asthma, chronic obstructive pulmonary disease, or heart block; caution if peripheral vascular disease or dyslipidaemia. Specialist supervision advised if used in heart failure.
bulletDo not combine with verapamil, due to the risk of bradycardia and reduced cardiac output.

Verapamil

bulletAvoid in heart failure or heart block.
bulletDo not combine with a beta-blocker, due to the risk of bradycardia and reduced cardiac output.
bulletAvoid in Wolff-Parkinson-White syndrome, as may cause the ventricular rate to accelerate.

This is not a fully comprehensive list of side effects and cautions. See BNF for full details.

 

Refer or investigate?

 

Refer ?
bulletVery symptomatic and in need of urgent rate control (emergency admission).
bulletPatient suitable for cardioversion, e.g.
bulletRecent onset atrial fibrillation. The time of onset is not always easy to determine and there is a case for referring all patients with newly diagnosed AF for at least one attempt at cardioversion. Patients with acute onset AF should ideally see a specialist within 48 hours in order to decide whether to cardiovert (success rates for cardioversion reduce the longer the person is in AF and anticoagulation prior to and following cardioversion is necessary if the person has been in AF for longer than 2 days)
bulletSuccessful treatment of any precipitating causes (e.g. thyrotoxicosis, chest infection)
bulletYoung age (although age should not be an automatic barrier)
bulletInadequate control despite maximal GP treatment.
bulletFurther assessment needed, e.g. suspected valvular disease, moderate to severe heart failure.
bulletSyncopal attacks.
bulletSuspected Wolff-Parkinson-White (WPW) syndrome.

Investigate ?

bulletECG to confirm the diagnosis.
bulletBase-line blood tests: FBC, electrolytes, thyroid function tests (plus coagulation screen and LFTs if anticoagulation being considered).
bulletConsider CXR (can give information on the size of the heart and whether heart failure is present).
bulletThe routine use of echocardiography continues to be debated. It may provide useful information on the presence of associated valvular disease and ventricular failure, and a recent consensus statement recommends that it should be part of the optimal assessment of patients with AF. However, for the majority of patients it is unlikely to affect the decision on whether to recommend anticoagulation or not. Local guidelines may be available regarding the use of this.

 

Dr/Patient shared advice

 

bulletTreatment of atrial fibrillation aims to bring the heart rate to below 90 per minute at rest.
bulletThere are three groups of medicines commonly used to control heart rate in AF.

- Betablockers

- Verapamil

- Digoxin

bulletOne medicine is advised at first. The one chosen may depend on whether you have other conditions, such as heart failure, asthma, or chronic obstructive airways disease. bulletA combination of two medicines may be needed if one alone does not control the heart rate. bulletSide effects are not common but tell your doctor if they occur (particularly with digoxin, as side effects with this often mean the dose is too high for you). It may be possible to switch to a different medicine. Possible side effects include the following.

- Betablockers: cool hands and feet, poor sleep, tiredness, impotence.

- Verapamil: constipation.

- Digoxin: feeling sick, vomiting, diarrhoea, mental confusion, blurred vision.

 

Drug rationale

 

Drugs not included
bulletAmiodarone requires specialist initiation. It may be useful for rate control in refractory cases but has a high incidence of side effects.
bulletDigitoxin is not commonly used in the UK and is more expensive than digoxin. It may be considered if there is an absolute requirement for a cardiac glycoside and the patient has severe renal impairment.
bulletDihydropyridine calcium-channel blockers (e.g. nifedipine) are not rate limiting and therefore have no place in the treatment of atrial fibrillation.
bulletDiltiazem is not licensed for the treatment of arrhythmias. In addition, it is difficult to recommend dosing (trials have been small and dosing has varied enormously).
bulletOther anti-arrhythmic drugs require specialist initiation and are used for maintenance of sinus rhythm after cardioversion, or pharmacological cardioversion, rather than purely for ventricular rate control.
bulletSotalol requires specialist initiation and is only licensed for paroxysmal atrial fibrillation.

Drugs included

bulletBeta-blockers reduce the ventricular rate at rest and during exercise. They should be considered as first line therapy, especially in patients with co-existing hypertension or angina [Royal College of Physicians of Edinburgh, 1999]. Atenolol, metoprolol, and propranolol are included since they are licensed for the treatment of arrhythmias and are less expensive than other beta-blockers.
bulletDigoxin reduces the ventricular rate at rest but is less effective at controlling the heart rate during exercise. It is the preferred choice if the patient has co-existing heart failure and can be used in combination with a beta-blocker or a rate limiting calcium-channel blocker if rate control is not achieved with adequate monotherapy [Royal College of Physicians of Edinburgh, 1999].
bulletVerapamil is licensed for use in arrhythmias. In atrial fibrillation, it reduces the ventricular rate at rest and during exercise. It should also be considered as first line therapy, especially in patients with co-existing hypertension or angina [Royal College of Physicians of Edinburgh, 1999]. Standard doses of verapamil are included, as modified-release verapamil is not licensed for the treatment of arrhythmias.

 

Therapy Group: Starting digoxin

 

readCode quantity £NHS £OTC csmWarning BioAvail

 

Digoxin 500microg daily then 250microg daily

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 250microgram tablets

b113. 56 tablet(s) license £1.18 No warning OK

Take two tablets once a day for 3 days, then take one tablet once a day.

 

Digoxin 500microg daily then 125microg daily

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 125microgram tablets

b112. 56 tablet(s) license £1.18 No warning OK

Take four tablets once a day for 3 days, then take one tablet once a day.

 

Digoxin 250microg daily then 125 microg daily

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 125microgram tablets

b112. 56 tablet(s) license £1.18 No warning OK

Take two tablets once a day for 3 days, then take one tablet once a day.

 

Digoxin 250microg daily then 62.5 microg daily

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 62.5micrograms tablets

b111. 56 tablet(s) license £1.52 No warning OK

Take four tablets once a day for 3 days, then take one tablet once a day.

 

Therapy Group: Continuing digoxin

 

readCode quantity £NHS £OTC csmWarning BioAvail

 

Digoxin 250micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 250microgram tablets

b113. 56 tablet(s) license £1.18 No warning OK

Take one tablet once a day

 

Digoxin 125 micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 125microgram tablets

b112. 56 tablet(s) license £1.18 No warning OK

Take one tablet once a day

 

Digoxin 62.5micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 62.5micrograms tablets

b111. 56 tablet(s) license £1.52 No warning OK

Take one tablet once a day

 

Digoxin 187.5 micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 62.5micrograms tablets

b111. 168 tablet(s) license £4.56 No warning OK

Take three tablets once a day

 

Digoxin 375micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 125microgram tablets

b112. 168 tablet(s) license £3.54 No warning OK

Take three tablets once a day

 

Digoxin 500micrograms once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Digoxin 250microgram tablets

b113. 112 tablet(s) license £2.36 No warning OK

Take two tablets once a day

 

Therapy Group: Beta blocker

 

readCode quantity £NHS £OTC csmWarning BioAvail

 

Atenolol 50mg once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Atenolol 50mg tablets

bd35. 56 tablet(s) license £1.44 Advice in BNF OK

Take one tablet once a day

 

Atenolol 100mg once a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Atenolol 100mg tablets

bd36. 56 tablet(s) license £1.82 Advice in BNF OK

Take one tablet once a day

 

Metroprolol 50mg twice a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Metoprolol 50mg tablets

bd6x. 112 tablet(s) license £4.44 Advice in BNF OK

Take one tablet twice a day

 

Metoprolol 100mg twice a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Metoprolol 100mg tablets

bd6w. 112 tablet(s) license £6.96 Advice in BNF OK

Take one tablet twice a day

 

Propranolol 10mg three times a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Propranolol 10mg tablets

bd11. 168 tablet(s) license £3.54 Advice in BNF OK

Take one tablet three times a day

 

Propranolol 40mg three times a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Propranolol 40mg tablets

bd12. 168 tablet(s) license £3.90 Advice in BNF OK

Take one tablet three times a day

 

Therapy Group: Verapamil

 

readCode quantity £NHS £OTC csmWarning BioAvail

 

Verapamil 40mg three times a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Verapamil 40mg tablets

bb31. 168 tablet(s) license £3.26 No warning OK

Take one tablet three times a day

 

Verapamil 80mg three times a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Verapamil 80mg tablets

bb32. 168 tablet(s) license £4.22 No warning OK

Take one tablet three times a day

 

Verapamil 120mg three times a day

 

NHS-PRESCRIPTION for age: 192 to 3060

Verapamil 120mg tablets

bb33. 168 tablet(s) license £7.98 No warning OK

Take one tablet three times a day

 

Scenario: Deciding antithrombotic treatment

 

 

Which therapy?

 

REMEMBER TO CONSIDER REFERRAL FOR ATTEMPTED CARDIOVERSION (SEE REFERRAL ADVICE)
bulletConfirm diagnosis by ECG.
bulletTreat any precipitating cause, e.g. thyrotoxicosis, chest infection.
bulletControl heart rate if appropriate (see relevant section).

 

bulletOffer treatment with warfarin, if not contraindicated, if:

 

    1. mitral valve disease
    2. previous thromboembolic stroke, TIA, or other arterial thromboembolism
    3. patient > = 65 years of age
    4. patient < 65 years of age with hypertension, diabetes, heart failure, or left ventricular dysfunction.
bulletConsider echocardiography if none of the above and treat with warfarin if:
    1. left atrial enlargement
    2. left ventricular dysfunction
    3. mitral valve disease.
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