The strength of recommendation grading [A–D (GPP)] and levels of evidence (1++–4) for interventional studies and strength of recommendation grading [A (DS)–D (DS)] and level of evidence (Ia–IV) for diagnostic studies are defined at the end of the "Major Recommendations" field.
Identification and Diagnosis
Presenting Symptoms/Pulse Palpitation
C - In patients presenting with any of the following:
- breathlessness/dyspnoea
- palpitations
- syncope/dizziness
- chest discomfort
- stroke/transischemic attack (TIA)
manual pulse palpation should be performed to assess for the presence of an irregular pulse that may indicate underlying atrial fibrillation (AF).
Electrocardiography
B (DS) - An electrocardiogram (ECG) should be performed in all patients, whether symptomatic or not, in whom AF is suspected because an irregular pulse has been detected.
Ambulatory ECG Recording
B (DS) - In patients with suspected paroxysmal AF undetected by standard ECG recording:
- a 24-hour ambulatory ECG monitor should be used in those with suspected asymptomatic episodes or symptomatic episodes less than 24 hours apart
- an event recorder ECG should be used in those with symptomatic episodes more than 24 hours apart
Echocardiography
Transthoracic echocardiography (TTE) should be performed in patients with AF:
- D (GPP) - for whom a baseline echocardiogram is important for long-term management, such as younger patients
- C - for whom a rhythm-control strategy that includes cardioversion (electrical or pharmacological) is being considered
- D (GPP) - in whom there is a high risk or a suspicion of underlying structural/functional heart disease (such as heart failure or heart murmur) that influences their subsequent management (for example, choice of antiarrhythmic drug)
- C - in whom refinement of clinical risk stratification for antithrombotic therapy is needed (see section below titled "Risk factors for Stroke and Thromboembolism")
D (GPP) - TTE should not be routinely performed solely for the purpose of further stroke risk stratification in patients with AF for whom the need to initiate anticoagulation therapy has already been agreed on appropriate clinical criteria (see section below titled "Risk factors for Stroke and Thromboembolism").
Transoesophageal echocardiography (TOE) should be performed in patients with AF:
- D (GPP) - when TTE demonstrates an abnormality (such as valvular heart disease) that warrants further specific assessment
- D (GPP) - in whom TTE is technically difficult and/or of questionable quality and where there is a need to exclude cardiac abnormalities
- D (GPP) - for whom TOE-guided cardioversion is being considered
Cardioversion
Electrical Versus Pharmacological Cardioversion
In patients with AF without haemodynamic instability for whom cardioversion is indicated:
- D (GPP) - the advantages and disadvantages of both pharmacological and electrical cardioversion should be discussed with patients before initiating treatment
- B - where AF onset was within 48 hours previously, either pharmacological or electrical cardioversion should be performed
- D (GPP) - for those with more prolonged AF (onset more than 48 hours previously) electrical cardioversion should be the preferred initial treatment option
Pharmacological Cardioversion
In patients with persistent AF, where the decision to perform pharmacological cardioversion using an intravenous antiarrhythmic agent has been made:
- B - in the absence of structural heart disease,* a Class 1c drug (such as flecainide or propafenone) should be the drug of choice
- D (GPP) - in the presence of structural heart disease,* amiodarone should be the drug of choice
*Coronary artery disease or left ventricular dysfunction
Electrical Cardioversion With Concomitant Antiarrhythmic Drugs
B - When patients with AF are to undergo elective electrical cardioversion and there is cause for heightened concern about successfully restoring sinus rhythm (such as previous failure to cardiovert or early recurrence of AF), concomitant amiodarone or sotalol* should be given for at least 4 weeks before the cardioversion.
*Sotalol to be progressively titrated from 80 mg twice daily up to 240 mg twice daily.
Transoesophageal Echocardiography-Guided Cardioversion
In patients with AF of greater than 48 hours duration, in whom elective cardioversion is indicated:
- B - both TOE-guided cardioversion and conventional cardioversion should be considered equally effective
- a TOE-guided cardioversion strategy should be considered:
- D (GPP) - where experienced staff and appropriate facilities are available, and
- C - where a minimal period of pre-cardioversion anticoagulation is indicated due to patient choice or bleeding risks
Treatment for Persistent AF
Rate Control Versus Rhythm Control
D (GPP) - As some patients with persistent AF will satisfy criteria for either an initial rate-control or rhythm-control strategy (for example, aged over 65 but also symptomatic):
- the indications for each option should not be regarded as mutually exclusive and the potential advantages and disadvantages of each strategy should be explained to patients before agreeing which to adopt
- any comorbidities that might indicate one approach rather than the other should be taken into account
- irrespective of whether a rate-control or a rhythm-control strategy is adopted in patients with persistent AF, appropriate antithrombotic therapy should be used
A rate-control strategy should be the preferred initial option in the following patients with persistent AF:
- B - over 65 years old
- B - with coronary artery disease
- D (GPP) - with contraindications to antiarrhythmic drugs
- D (GPP) - unsuitable for cardioversion*
- B - without congestive heart failure
A rhythm-control strategy should be the preferred initial option in the following patients with persistent AF:
- D (GPP) - those who are symptomatic
- C - younger patients
- D (GPP) - those presenting for the first time with lone AF
- D (GPP) - those with AF secondary to a treated/corrected precipitant
- C - those with congestive heart failure
*Patients unsuitable for cardioversion include those with:
- contraindications to anticoagulation
- structural heart disease (e.g., large left atrium >5.5 cm, mitral stenosis) that precludes long-term maintenance of sinus rhythm
- a long duration of AF (usually >12 months)
- a history of multiple failed attempts at cardioversion and/or relapses, even with concomitant use of antiarrhythmic drugs or non-pharmacological approaches
- an ongoing but reversible cause of atrial fibrillation (e.g., thyrotoxicosis)
Rhythm Control For Persistent AF
D (GPP) - An antiarrhythmic drug is not required to maintain sinus rhythm in patients with persistent AF in whom a precipitant (such as chest infection or fever) has been corrected and cardioversion has been performed successfully, providing there are no risk factors for recurrence.
In patients with persistent AF who require antiarrhythmic drugs to maintain sinus rhythm and who have structural heart disease*:
- D (GPP) - a standard beta-blocker should be the initial treatment option
- A - where a standard beta-blocker is ineffective, contraindicated or not tolerated amiodarone should be used
In patients with persistent AF who require antiarrhythmic drugs to maintain sinus rhythm and who do not have structural heart disease*:
- D (GPP) - a standard beta-blocker should be the initial treatment option
- where a standard beta-blocker is ineffective, contraindicated or not tolerated
- C - a Class Ic agent or
- D (GPP) - sotalol**
should be given
B - where other drug classes are ineffective, contraindicated or not tolerated amiodarone should be administered.
*Coronary artery disease or left ventricular dysfunction.
**Progressively titrated from 80 mg twice daily up to 240 mg twice daily.
Antithrombotic Therapy For Persistent AF
C - Before cardioversion, patients should be maintained on therapeutic anticoagulation with warfarin (INR 2.5, range 2.0 to 3.0) for a minimum of 3 weeks.
D (GPP) - Following successful cardioversion, patients should remain on therapeutic anticoagulation with warfarin (INR 2.5, range 2.0 to 3.0) for a minimum of 4 weeks.
In patients with persistent AF where cardioversion cannot be postponed for 3 weeks:
- D - heparin should be given and the cardioversion performed, and
- D (GPP) - warfarin should then be given for a minimum of 4 weeks post cardioversion.
D (GPP) - Anticoagulation should be continued for the long term in patients with AF who have undergone cardioversion where there is a high risk or AF recurrence* or where it is recommended by the stroke risk stratification algorithm (see Figure 11.1 in the original guideline document).
D (GPP) - In patients with AF of confirmed duration of less than 48 hours undergoing cardioversion, anticoagulation following successful restoration of sinus rhythm is not required.
D (GPP) - Patients with atrial flutter should be given antithrombotic therapy in the same manner as those with AF.
*Factors indicating a high risk of AF recurrence include:
- a history of failed attempts at cardioversion
- structural heart disease (mitral valve disease, left ventricular dysfunction or an enlarged left atrium)
- a prolonged history of AF (greater than 12 months)
- previous recurrences of AF
Treatment For Permanent AF
Rate Control For Permanent AF
In patients with permanent AF, who need treatment for rate control:
- A - beta-blockers or rate-limiting calcium antagonists should be the preferred initial monotherapy in all patients.
- D (GPP) - digoxin should only be considered as monotherapy in predominately sedentary patients.
In patients with permanent AF where monotherapy is inadequate:
B - to control the heart rate only during normal activities, beta-blockers or rate-limiting calcium antagonists should be given with digoxin
B - to control the heart rate during both normal activities and exercise, rate-limiting calcium antagonists should be given with digoxin.
Antithrombotic Therapy For Permanent AF
D (GPP) - In patients with permanent AF a risk–benefit assessment should be performed and discussed with the patient to inform the decision whether or not to give antithrombotic therapy.
In patients with permanent AF where antithrombotic therapy is given to prevent strokes and/or thromboembolism (see section below titled "Risk factors for Stroke and Thromboembolism"):
A - adjusted-dose warfarin should be given as the most effective treatment
A - adjusted-dose warfarin should reach a target INR of 2.5 (range 2.0 to 3.0)
B - where warfarin is not appropriate, aspirin should be given at 75 to 300 mg/day
B - where warfarin is appropriate, aspirin should not be co-administered with warfarin purely as thromboprophylaxis, as it provides no additional benefit.
Treatment For Paroxysmal AF
Rhythm Control For Paroxysmal AF
D (GPP) - Where patients have infrequent paroxysms and few symptoms, or where symptoms are induced by known precipitants (such as alcohol, caffeine), a 'no drug treatment' strategy or a pill-in-the-pocket strategy should be considered and discussed with the patient.
D (GPP) - In patients with symptomatic paroxysms (with or without structural heart disease,* including coronary artery disease) a standard beta-blocker should be the initial treatment option.
In patients with paroxysmal AF and no structural heart disease:*
- where symptomatic suppression is not achieved with standard beta-blockers, either
- D (GPP) - a Class Ic agent (such as flecainide or propafenone), or
- D (GPP) - sotalol**
should be given.
- where symptomatic suppression is not achieved with standard beta-blockers, Class Ic agents or sotalol, either
- B - amiodarone, or
- A - referral for non-pharmacological intervention (see section below titled "Referral") should be considered.
In patients with paroxysmal AF and coronary artery disease:
- D (GPP) - where standard beta-blockers do not achieve symptomatic suppression, sotalol should be given*
- where neither standard beta-blockers nor sotalol achieve symptomatic suppression, either
- B - amiodarone, or
- A - referral for non-pharmacological intervention (see section below titled "Referral")
should be considered.
In patients with paroxysmal AF with poor left ventricular function:
- D (GPP) - where standard beta-blockers are given as part of the routine management strategy and adequately suppress paroxysms, no further treatment for paroxysms is needed
- where standard beta-blockers do not adequately suppress paroxysms, either
- B - amiodarone or
- A - referral for non-pharmacological intervention (see section below titled "Referral")
should be considered.
D (GPP) - Patients on long-term medication for paroxysmal AF should be kept under review to assess the need for continued treatment and the development of any adverse effects.
*Coronary artery disease or left ventricular dysfunction.
**Progressively titrated from 80 mg twice daily up to 240 mg twice daily.
Treatment Strategy For Paroxysmal AF
C - In patients with paroxysmal AF, a pill-in-the-pocket strategy should be considered in those who:
- have no history of left ventricular dysfunction, or valvular or ischaemic heart disease; and
- have a history of infrequent symptomatic episodes of paroxysmal AF; and
- have a systolic blood pressure greater than 100 mm Hg and a resting heart rate above 70 bpm; and
- are able to understand how to, and when to, take the medication
Antithrombotic Therapy For Paroxysmal AF
B - Decisions on the need for antithrombotic therapy in patients with paroxysmal AF should not be based on the frequency or duration of paroxysms (symptomatic or asymptomatic) but on appropriate risk stratification, as for permanent AF (see section below titled "Risk Factors for Stroke and Thromboembolism").
Treatment For Acute-Onset AF
Acute AF in Haemodynamically Unstable Patients
D - In patients with a life-threatening deterioration in haemodynamic stability following the onset of AF, emergency electrical cardioversion should be performed, irrespective of the duration of the AF.
In patients with non life-threatening haemodynamic instability following the onset of AF:
- D - electrical cardioversion should be performed
- D - where there is a delay in organising electrical cardioversion, intravenous amiodarone should be used
- D (GPP) - in those with known Wolff–Parkinson–White syndrome:
- flecainide may be used as an alternative for attempting pharmacological cardioversion
- atrioventricular node-blocking agents (such as diltiazem, verapamil or digoxin) should not be used
D - In patients with known permanent AF where haemodynamic instability is caused mainly by a poorly controlled ventricular rate, a pharmacological rate-control strategy should be used.
Where urgent pharmacological rate-control is indicated, intravenous treatment should be with one of the following:
- D - beta-blockers or rate-limiting calcium antagonists
- D - amiodarone, where beta-blockers or calcium antagonists are contraindicated or ineffective
Antithrombotic Therapy For Acute-Onset AF
D (GPP) - In patients with acute AF who are receiving no, or subtherapeutic, anticoagulation therapy:
- in the absence of contraindications, heparin should be started at initial presentation
- heparin should be continued until a full assessment has been made and appropriate antithrombotic therapy has been started, based on risk stratification (see section below titled "Risk factors for Stroke and Thromboembolism")
D (GPP) - In patients with a confirmed diagnosis of acute AF of recent onset (less than 48 hours since onset), oral anticoagulation should be used if:
- stable sinus rhythm is not successfully restored within the same 48-hour period following onset of acute AF, or
- there are factors indicating a high risk of AF recurrence,* or
- it is recommended by the stroke risk stratification algorithm (see Figure 11.1 in the original guideline document)
D (GPP) - In patients with acute AF where there is uncertainty over the precise time since onset, oral anticoagulation should be used, as for persistent AF (see section above titled "Rhythm Control for Persistent AF").
D (GPP) - In cases of acute AF where the patient is haemodynamically unstable, any emergency intervention should be performed as soon as possible and the initiation of anticoagulation should not delay any emergency intervention.
*Factors indicating a high risk of AF recurrence include:
- a history of failed attempts at cardioversion
- structural heart disease (mitral valve disease, left ventricular dysfunction or an enlarged left atrium)
- a prolonged history of AF (greater than 12 months)
- previous recurrences of AF
Postoperative AF
Drug Prophylaxis For Postoperative AF
D (GPP) - In the prophylaxis and management of postoperative AF, the appropriate use of antithrombotic therapy and correction of identifiable precipitants (such as electrolyte imbalance or hypoxia) is recommended.
In patients undergoing cardiothoracic surgery:
- the risk of postoperative AF should be reduced by the administration of one of the following:
- A - amiodarone
- A - a beta-blocker
- A- sotalol
- B - a rate-limiting calcium antagonist
- B - digoxin should not be used.
A - In patients undergoing cardiac surgery on pre-existing beta-blocker therapy, this treatment should be continued unless contraindications develop (such as postoperative bradycardia or hypotension).
Treatment for Postoperative AF
C - Unless contraindicated, a rhythm-control strategy should be the initial management option for the treatment of postoperative AF following cardiothoracic surgery.
D (GPP) - Unless contraindicated, postoperative AF following non-cardiothoracic surgery should be managed as for acute-onset AF with any other precipitant.
Antithrombotic Therapy
Initiating Antithrombotic Therapy
D (GPP) - In patients with newly diagnosed AF for whom antithrombotic therapy is indicated (see section below titled "Risk Factors for Stroke and Thromboembolism"), such treatment should be initiated with minimal delay after the appropriate management of comorbidities.
Antithrombotic Therapy in Acute Stroke Patients*
*NICE is developing a clinical guideline on the diagnosis and management of stroke (publication is expected for 2008).
D (GPP) - In all patients with AF who have had an acute stroke, any uncontrolled hypertension should be appropriately managed before antithrombotic therapy is started.
D (GPP) - In patients with AF and an acute stroke:
- imaging (CT scan or MRI) should be performed to exclude cerebral haemorrhage
- in the absence of haemorrhage, anticoagulation therapy should begin after 2 weeks
- in the presence of haemorrhage, anticoagulation therapy should not be given
- in the presence of a large cerebral infarction, the initiation of anticoagulation therapy should be delayed
D (GPP) - In patients with AF and an acute TIA:
- imaging (CT scan or MRI) should be performed to exclude recent cerebral infarction or haemorrhage
- in the absence of cerebral infarction or haemorrhage, anticoagulation therapy should begin as soon as possible
Antithrombotic Therapy Following a Stroke or TIA
In patients with AF who are either post-stroke, or have had a TIA:
- A - warfarin should be administered as the most effective thromboprophylactic agent
- D (GPP) - aspirin or dipyridamole should not be administered as thromboprophylactic agents unless indicated for the treatment of comorbidities or vascular disease.
D (GPP) - Treatment of post-stroke or post-TIA patients with warfarin should only begin after treatment of relevant comorbidities (such as hypertension) and assessment of the risk–benefit ratio.
Antithrombotic Therapy For Asymptomatic AF
D (GPP) - Patients with asymptomatic AF should receive thromboprophylaxis as for symptomatic AF (refer to sections above for persistent AF, permanent AF and paroxysmal AF).
Risks of Long-Term Anticoagulation
D (GPP) - Both the antithrombotic benefits and the potential bleeding risks of long-term anticoagulation should be explained to and discussed with the patient.
The assessment of bleeding risk should be part of the clinical assessment of patients before starting anticoagulation therapy. Particular attention should be paid to patients who:
- D - are over 75 years of age
- C - are taking antiplatelet drugs (such as aspirin or clopidogrel) or non-steroidal anti-inflammatory drugs
- C - are on multiple other drug treatments (polypharmacy)
- C - have uncontrolled hypertension
- C - have a history of bleeding (for example, peptic ulcer or cerebral haemorrhage)
- D (GPP) - have a history of poorly controlled anticoagulation therapy
Risk Factors For Stroke And Thromboembolism
C - The stroke risk stratification algorithm (section 11.7 of the original guideline document) should be used in patients with AF to assess their risk of stroke and thromboembolism, and appropriate thromboprophylaxis given.
D (GPP) - Risk stratification should be reconsidered whenever individual risk factors are reviewed.
Monitoring and Referral
Anticoagulation Self-Monitoring
C - In patients with AF who require long-term anticoagulation, self-monitoring should be considered if preferred by the patient and the following criteria are met:
- the patient is both physically and cognitively able to perform the self-monitoring test, or in those cases where the patient is not physically or cognitively able to perform self-monitoring, a designated carer is able to do so
- an adequate supportive educational programme is in place to train patients and/or carers
- the patient's ability to self-manage is regularly reviewed
- the equipment for self-monitoring is regularly checked via a quality control programme
Follow-Up Post Cardioversion
D - Following successful cardioversion of AF routine follow-up to assess the maintenance of sinus rhythm should take place at 1 month and 6 months.
D - At the 1-month follow-up the frequency of subsequent reviews should be tailored to the individual patient taking into account comorbidities and concomitant drug therapies.
D (GPP) - At each review the clinician should take the opportunity to re-assess the need for, and the risks and benefits of, continued anticoagulation.
D - At 6 months, if patients remain in sinus rhythm and have no other need for hospital follow-up, they should be discharged from secondary care with an appropriate management plan agreed with their GP.
D (GPP) - Patients should be advised to seek medical attention if symptoms recur.
D (GPP) - Any patient found at follow-up to have relapsed into AF should be fully re-evaluated for a rate-control or rhythm-control strategy (see section above titled "Antithrombotic Therapy for Persistent AF").
Referral
Referral for further specialist intervention (for example, pulmonary vein isolation, pacemaker therapy, arrhythmia surgery, AVJ catheter ablation or use of atrial defibrillators) should be considered in the following patients:
B - those in whom pharmacological therapy has failed
B - those with lone AF
C - those with ECG evidence of an underlying electrophysiological disorder (e.g., Wolff–Parkinson–White syndrome).
D (GPP) - The reasons for referral for specialist intervention should be explained and discussed with the patient.
Definitions:
Levels of Evidence for Intervention Studies
1++ High quality meta-analysis (MA), systematic reviews (SR) of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+ Well conducted MA, SR or RCTs, or RCTs with a low risk of bias
1- MA, SR of RCTs, or RCTs with a high risk of bias
2++ High quality SR of case-control or cohort studies.
High quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal
2+ Well conducted case-control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal
2- Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal (Not used as a basis for making a recommendation)
3 Non-analytic studies (for example, case reports, case series)
4 Expert opinion, formal consensus
Levels of Evidence for Studies of the Accuracy of Diagnostic Tests
Ia Systematic review (with homogeneity)* of level-1 studies**
Ib Level-1 studies**
II Level-2 studies***
Systematic reviews of level-2 studies
III Level-3 studies****
Systematic reviews of level-3 studies
IV Consensus, expert committee reports or opinions and/or clinical experience without explicit critical appraisal; or based on physiology, bench research or 'first principles'
*Homogeneity means there are no or minor variations in the directions and degrees of results between individual studies that are included in the systematic review.
**Level-1 studies are studies:
- that use a blind comparison of the test with a validated reference standard (gold standard)
- in a sample of patients that reflects the population to whom the test would apply
***Level-2 studies are studies that have only one of the following:
- narrow population (the sample does not reflect the population to whom the test would apply)
- use a poor reference standard (defined as that where the 'test' is included in the 'reference', or where the "testing' affects the 'reference')
- the comparison between the test and reference standard is not blind
- case-control studies
****Level-3 studies are studies that have at least two or three of the features listed for level-2 studies.
Grading of Recommendations for Intervention Studies
Grade A:
- Level 1++ and directly applicable to the target population, or
- Level 1+ and directly applicable to the target population AND consistency of results
- Evidence from National Institute for Health and Clinical Excellence (NICE) technology appraisal
Grade B:
- Level 2 ++, directly applicable to the target population and demonstrating overall consistency of results, or
- Extrapolated evidence from studies rated as 1++ or 1+
Grade C:
- Level 2+, directly applicable to the target population and demonstrating overall consistency of results, or
- Extrapolated evidence from 2++
Grade D:
- Level 3 or 4, or
- Extrapolated from 2+, or
- Formal consensus
D (GPP):
A good practice point (GPP) is a recommendation for best practice based on the experience of the Guideline Development Group
Grading of Recommendations on Diagnostic Tests
Grade A (DS) Studies with level of evidence Ia or Ib
Grade B (DS) Studies with level of evidence II
Grade C (DS) Studies with level of evidence III
Grade D (DS) Studies with level of evidence IV
