Atrial fibrillation (acute onset) Search date April 2014 Gregory YH Lip and Stavros Apostolakis ABSTRACT INTRODUCTION: Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil.
QUESTIONS What are the effects of interventions to prevent embolism in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 What are the effects of interventions for conversion to sinus rhythm in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 What are the effects of interventions to control heart rate in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 INTERVENTIONS PREVENTION OF EMBOLISM
RATE CONTROL
Unknown effectiveness
Likely to be beneficial
Antithrombotic treatment before cardioversion . . . . . 4
Amiodarone for rate control* . . . . . . . . . . . . . . . . . . 31 Digoxin for rate control . . . . . . . . . . . . . . . . . . . . . . 32
RHYTHM CONVERSION
Diltiazem for rate control . . . . . . . . . . . . . . . . . . . . 34
Likely to be beneficial
Timolol for rate control . . . . . . . . . . . . . . . . . . . . . . 37
Direct current cardioversion for rhythm control . . . . 27 Trade off between benefits and harms
Verapamil for rate control . . . . . . . . . . . . . . . . . . . . 38 Unknown effectiveness
Flecainide for rhythm control . . . . . . . . . . . . . . . . . . 4
Bisoprolol for rate control New . . . . . . . . . . . . . . . 35
Propafenone for rhythm control . . . . . . . . . . . . . . . 11
Metoprolol for rate control New . . . . . . . . . . . . . . . 35
Amiodarone for rhythm control . . . . . . . . . . . . . . . . 20
Atenolol for rate control New . . . . . . . . . . . . . . . . . 36 Nebivolol for rate control New . . . . . . . . . . . . . . . . 36
Unknown effectiveness
Carvedilol for rate control New . . . . . . . . . . . . . . . 37
Sotalol for rhythm control . . . . . . . . . . . . . . . . . . . . 28
Sotalol for rate control . . . . . . . . . . . . . . . . . . . . . . 38
Verapamil for rhythm control . . . . . . . . . . . . . . . . . . 30 Footnote Unlikely to be beneficial
*Categorisation based on consensus.
Digoxin for rhythm control . . . . . . . . . . . . . . . . . . . . 29
Key points • Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of less than 48 hours' duration. It resolves spontaneously within 24 to 48 hours in more than 50% of people. In this review, we have included studies on patients with onset up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, CVD, alcohol abuse, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure.
© BMJ Publishing Group Ltd 2014. All rights reserved.
..................... 1 .....................
Clinical Evidence 2014;11:210
Cardiovascular disorders
..................................................
• The consensus is that people with haemodynamically unstable atrial fibrillation should have immediate direct current cardioversion. In people who are haemodynamically stable, direct current cardioversion increases reversion to sinus rhythm compared with intravenous propafenone. There is consensus that antithrombotic treatment with heparin should be given before cardioversion of recentonset atrial fibrillation to reduce the risk of embolism in people who are haemodynamically stable, but we found no studies to show whether this is beneficial. • Oral or intravenous flecainide, propafenone, or amiodarone increase the likelihood of reversion to sinus rhythm compared with placebo in people with haemodynamically stable acute atrial fibrillation. • CAUTION: Flecainide and propafenone should not be used in people with ischaemic heart disease as they can cause (life-threatening) arrhythmias. • We don't know whether sotalol increases reversion to sinus rhythm in people with haemodynamically stable atrial fibrillation, as few adequate trials have been conducted. Digoxin does not seem to increase reversion to sinus rhythm compared with placebo. We don't know whether verapamil increases reversion to sinus rhythm compared with placebo. • No one drug has been shown to be more effective at controlling heart rate. However, there is general consensus that intravenous bolus amiodarone is more effective than digoxin. • Treatment with digoxin may control heart rate in people with haemodynamically stable atrial fibrillation, despite its being unlikely to restore sinus rhythm. • We don't know whether diltiazem, timolol, and verapamil are effective at controlling heart rate, but they are unlikely to restore sinus rhythm. We don't know whether sotalol, bisoprolol, metoprolol, atenolol, nebivolol, or carvedilol are effective at controlling heart rate in people with acute atrial fibrillation who are haemodynamically stable. However, sotalol may cause arrhythmias at high doses. Clinical context DEFINITION
Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Acute atrial fibrillation includes both the first symptomatic onset of chronic or persistent atrial fibrillation and episodes of paroxysmal atrial fibrillation. It is sometimes difficult to distinguish new-onset atrial fibrillation from previously undiagnosed long-standing atrial fibrillation. By contrast, chronic atrial fibrillation is more sustained and can be described as paroxysmal (with spontaneous termination and sinus rhythm between recurrences), persistent, or permanent atrial fibrillation. This review deals with people with acute and recent-onset atrial fibrillation who are haemodynamically stable. The consensus is that people who are not haemodynamically stable should be treated with immediate direct current cardioversion. We have excluded studies in people with atrial fibrillation arising during or soon after cardiac surgery. Diagnosis Acute atrial fibrillation should be suspected in people presenting with dizziness, syncope, dyspnoea, or palpitations. Moreover, atrial fibrillation can contribute to a large number of other non-specific symptoms. Palpation of an irregular pulse is generally only considered sufficient to raise suspicion of atrial fibrillation; diagnosis requires confirmation with ECG. However, in those with paroxysmal atrial fibrillation, ambulatory monitoring [1] [2] may be required.
INCIDENCE/ PREVALENCE
We found limited evidence on the incidence or prevalence of acute atrial fibrillation. Extrapolation from the Framingham study suggests an incidence in men of 3/1000 person-years at age 55 years, [3] rising to 38/1000 person-years at age 94 years. In women, the incidence was 2/1000 personyears at age 55 years and 32.5/1000 person-years at age 94 years. The prevalence of atrial fibrillation ranged from 0.5% for people aged 50 to 59 years to 9% in people aged 80 to 89 years. Among acute emergency medical admissions in the UK, 3% to 6% had atrial fibrillation, and about [4] [5] 40% of these were newly diagnosed. Among acute hospital admissions in New Zealand, [6] 10% (95% CI 9% to 12%) had documented atrial fibrillation.
AETIOLOGY/ Common precipitants of acute atrial fibrillation are acute MI and the acute effects of alcohol. Age RISK FACTORS increases the risk of developing acute atrial fibrillation. Men are more likely than women to develop atrial fibrillation (38 years' follow-up from the Framingham Study; RR, after adjustment for age and [7] known predisposing conditions, 1.5). Atrial fibrillation can occur in association with underlying disease (both cardiac and non-cardiac) or can arise in the absence of any other condition. Epidemiological surveys found that risk factors for the development of acute atrial fibrillation include ischaemic heart disease, hypertension, heart failure, valve disease, diabetes, alcohol abuse, thyroid [3] disorders, and disorders of the lung and pleura. In a British survey of acute hospital admissions of people with atrial fibrillation, a history of ischaemic heart disease was present in 33%, heart © BMJ Publishing Group Ltd 2014. All rights reserved.
........................................................... 2
Cardiovascular disorders
Atrial fibrillation (acute onset)
[5]
failure in 24%, hypertension in 26%, and rheumatic heart disease in 7%. In some populations, the acute effects of alcohol explain a large proportion of the incidence of acute atrial fibrillation. [8] Paroxysms of atrial fibrillation are more common in athletes. PROGNOSIS
Spontaneous reversion: observational studies and placebo arms of RCTs found that more than 50% of people with acute atrial fibrillation revert spontaneously within 24 to 48 hours, especially if atrial fibrillation is associated with an identifiable precipitant such as alcohol or MI. Progression to chronic atrial fibrillation: we found no evidence about the proportion of people with acute atrial fibrillation who develop more chronic forms of atrial fibrillation (e.g., paroxysmal, persistent, or permanent atrial fibrillation). Mortality: we found little evidence about the effects on mortality of acute atrial fibrillation where no underlying cause is found. Acute atrial fibrillation during MI is an [9] independent predictor of both short- and long-term mortality. Heart failure: onset of atrial fibril[10] lation reduces cardiac output by 10% to 20%, irrespective of the underlying ventricular rate, [11] and can contribute to heart failure. People with acute atrial fibrillation who present with heart failure have worse prognoses. Stroke: acute atrial fibrillation is associated with a risk of imminent [12] [13] [14] [15] stroke. One case series using transoesophageal echocardiography in people who had developed acute atrial fibrillation within the preceding 48 hours found that 15% had atrial [16] thrombi. An ischaemic stroke associated with atrial fibrillation is more likely to be fatal, have a recurrence, or leave a serious functional deficit among survivors than a stroke not associated with [17] atrial fibrillation.
AIMS OF To reduce symptoms, morbidity, and mortality with minimum adverse effects. INTERVENTION OUTCOMES
Major outcomes include: thromboembolism, stroke or transient ischaemic attack, major bleeding, mortality, and adverse effects of treatment. Proxy measures include heart rhythm, ventricular rate, and time to restoration of sinus rhythm. The following outcomes are reported in this review: for the question on interventions to prevent embolism: thromboembolic events (thromboembolism, stroke, TIA); for the question on interventions for conversion to sinus rhythm: conversion to sinus rhythm; for the question on interventions to control heart rate: control of heart rate; for all questions: mortality, adverse effects. Frequent spontaneous reversion to sinus rhythm makes it difficult to interpret short-term studies of rhythm; treatments may accelerate restoration of sinus rhythm without increasing the proportion of people who eventually convert. The clinical importance of changes in mean heart rate is also unclear.
METHODS
Clinical Evidence search April 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2014, Embase 1980 to April 2014, and The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts of the studies retrieved from the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing at least 20 individuals (at least 10 per arm), of whom at least 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were studied, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table, p 42 ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
© BMJ Publishing Group Ltd 2014. All rights reserved.
...........................................................
3
Cardiovascular disorders
Atrial fibrillation (acute onset)
QUESTION
What are the effects of interventions to prevent embolism in people with recent-onset atrial fibrillation who are haemodynamically stable?
OPTION
ANTITHROMBOTIC TREATMENT BEFORE CARDIOVERSION. . . . . . . . . . . . . . . . . . . . . . . . .
•
For GRADE evaluation of interventions for Atrial fibrillation (acute onset), see table, p 42 .
•
There is consensus that antithrombotic treatment with heparin should be given before cardioversion to reduce risk of embolism in people who are haemodynamically stable, but we found no RCT evidence to show whether this is effective. Benefits and harms
Antithrombotic treatment before cardioversion: We found no systematic review or RCTs on the use of antithrombotic treatment versus placebo before cardioversion in people with acute atrial fibrillation of less than 7 days' duration. Comment:
One RCT compared low molecular weight heparin with unfractionated heparin (155 people with atrial fibrillation of between 2 and 19 days' duration, undergoing a transoesophageal echocardiog[18] raphy-guided cardioversion strategy). The RCT found no significant difference between low molecular weight heparin and unfractionated heparin in rates of thrombus observation, stroke, systemic embolism, or bleeding. However, low molecular weight heparin did allow earlier hospital discharge. Clinical guide: There is consensus to give heparin to people who have cardioversion within 48 hours of the onset of arrhythmia, but we found insufficient evidence from trials to support this. The decision to give anticoagulation both in the short-term and after cardioversion is usually based on [19] an individual's intrinsic risk of thromboembolism. Warfarin is not used as an anticoagulant in acute atrial fibrillation because of its slow onset of action. One transoesophageal echocardiography study in people with a recent embolic event found left atrial thrombus in 15% of people with acute [16] atrial fibrillation of less than 3 days' duration. This would suggest that such people may benefit from formal anticoagulation, or need to be evaluated by transoesophageal echocardiography before cardioversion.
QUESTION
What are the effects of interventions for conversion to sinus rhythm in people with recentonset atrial fibrillation who are haemodynamically stable?
OPTION
FLECAINIDE FOR RHYTHM CONTROL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
•
For GRADE evaluation of interventions for Atrial fibrillation (acute onset), see table, p 42 .
•
Oral or intravenous flecainide increases the likelihood of reversion to sinus rhythm compared with placebo in people with haemodynamically stable acute atrial fibrillation.
•
Flecainide is associated with serious adverse events, such as severe hypotension and torsades de pointes.
•
CAUTION: Flecainide should not be used in people with ischaemic heart disease as it can cause (life-threatening) arrhythmias. Amiodarone should be used in preference to flecainide in people with structural heart disease. Benefits and harms
Flecainide versus placebo: [20] [21] We found five RCTs.
[22]
[23]
[24]
Conversion to sinus rhythm Flecainide compared with placebo Oral or intravenous (iv) flecainide is more effective at increasing the rate of conversion to sinus rhythm at 1 to 24 hours in people with acute atrial fibrillation (moderate-quality evidence).
© BMJ Publishing Group Ltd 2014. All rights reserved.
...........................................................
4
Cardiovascular disorders
Atrial fibrillation (acute onset)
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Rate of conversion to sinus rhythm [20]
RCT 3-armed trial
62 people, aged Conversion to sinus rhythm , >75 years, onset of 8 hours atrial fibrillation 7 20/22 (91%) with oral flecainide days or less 10/21 (48%) with placebo
P 120 beats/minute; systolic blood pressure 90 mmHg or more, without severe heart failure; 108 people with at least 1 underlying condition that may explain [61] atrial arrhythmia; mean age 64 years) compared intravenous (iv) diltiazem with placebo. After randomisation, a dose of iv diltiazem (0.25 mg/kg over 2 minutes), or equivalent placebo, was given. If the first dose had no effect after 15 minutes, then the code was broken and diltiazem 0.35 mg/kg every 2 minutes was given, regardless of randomisation. The RCT found no difference in response rate to diltiazem in people with atrial fibrillation compared with those with atrial flutter. In the diltiazem-treated group, seven people developed asymptomatic hypotension (systolic blood
© BMJ Publishing Group Ltd 2014. All rights reserved.
..........................................................
34
Cardiovascular disorders
Atrial fibrillation (acute onset)
pressure 2
Directness points deducted for wide inclusion criteria and for use of different regimens
What are the effects of interventions to control heart rate in people with recent-onset atrial fibrillation who are haemodynamically stable? © BMJ Publishing Group Ltd 2014. All rights reserved.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cardiovascular disorders
Atrial fibrillation (acute onset)
Important outcomes Studies (Participants) 1 (100)
[43]
2 (333)
[53]
[54]
Control of heart rate, Conversion to sinus rhythm, Mortality Outcome
Comparison
Type of evidence
Quality
Consistency
Directness
Effect size
GRADE
Comment
Control of heart rate
Amiodarone versus digoxin
4
–2
–1
0
0
Very low
Quality points deducted for sparse data and incomplete reporting of results; consistency point deducted for different results at different endpoints
Control of heart rate
Digoxin versus placebo
4
0
0
–1
0
Moderate
Directness point deducted for wide inclusion criteria
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasirandomisation, sparse data [
QUESTIONS What are the effects of interventions to prevent embolism in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 What are the effects of interventions for conversion to sinus rhythm in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 What are the effects of interventions to control heart rate in people with recent-onset atrial fibrillation who are haemodynamically stable?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 INTERVENTIONS PREVENTION OF EMBOLISM
RATE CONTROL
Unknown effectiveness
Likely to be beneficial
Antithrombotic treatment before cardioversion . . . . . 4
Amiodarone for rate control* . . . . . . . . . . . . . . . . . . 31 Digoxin for rate control . . . . . . . . . . . . . . . . . . . . . . 32
RHYTHM CONVERSION
Diltiazem for rate control . . . . . . . . . . . . . . . . . . . . 34
Likely to be beneficial
Timolol for rate control . . . . . . . . . . . . . . . . . . . . . . 37
Direct current cardioversion for rhythm control . . . . 27 Trade off between benefits and harms
Verapamil for rate control . . . . . . . . . . . . . . . . . . . . 38 Unknown effectiveness
Flecainide for rhythm control . . . . . . . . . . . . . . . . . . 4
Bisoprolol for rate control New . . . . . . . . . . . . . . . 35
Propafenone for rhythm control . . . . . . . . . . . . . . . 11
Metoprolol for rate control New . . . . . . . . . . . . . . . 35
Amiodarone for rhythm control . . . . . . . . . . . . . . . . 20
Atenolol for rate control New . . . . . . . . . . . . . . . . . 36 Nebivolol for rate control New . . . . . . . . . . . . . . . . 36
Unknown effectiveness
Carvedilol for rate control New . . . . . . . . . . . . . . . 37
Sotalol for rhythm control . . . . . . . . . . . . . . . . . . . . 28
Sotalol for rate control . . . . . . . . . . . . . . . . . . . . . . 38
Verapamil for rhythm control . . . . . . . . . . . . . . . . . . 30 Footnote Unlikely to be beneficial
*Categorisation based on consensus.
Digoxin for rhythm control . . . . . . . . . . . . . . . . . . . . 29
Key points • Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of less than 48 hours' duration. It resolves spontaneously within 24 to 48 hours in more than 50% of people. In this review, we have included studies on patients with onset up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, CVD, alcohol abuse, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure.
© BMJ Publishing Group Ltd 2014. All rights reserved.
..................... 1 .....................
Clinical Evidence 2014;11:210
Cardiovascular disorders
..................................................
• The consensus is that people with haemodynamically unstable atrial fibrillation should have immediate direct current cardioversion. In people who are haemodynamically stable, direct current cardioversion increases reversion to sinus rhythm compared with intravenous propafenone. There is consensus that antithrombotic treatment with heparin should be given before cardioversion of recentonset atrial fibrillation to reduce the risk of embolism in people who are haemodynamically stable, but we found no studies to show whether this is beneficial. • Oral or intravenous flecainide, propafenone, or amiodarone increase the likelihood of reversion to sinus rhythm compared with placebo in people with haemodynamically stable acute atrial fibrillation. • CAUTION: Flecainide and propafenone should not be used in people with ischaemic heart disease as they can cause (life-threatening) arrhythmias. • We don't know whether sotalol increases reversion to sinus rhythm in people with haemodynamically stable atrial fibrillation, as few adequate trials have been conducted. Digoxin does not seem to increase reversion to sinus rhythm compared with placebo. We don't know whether verapamil increases reversion to sinus rhythm compared with placebo. • No one drug has been shown to be more effective at controlling heart rate. However, there is general consensus that intravenous bolus amiodarone is more effective than digoxin. • Treatment with digoxin may control heart rate in people with haemodynamically stable atrial fibrillation, despite its being unlikely to restore sinus rhythm. • We don't know whether diltiazem, timolol, and verapamil are effective at controlling heart rate, but they are unlikely to restore sinus rhythm. We don't know whether sotalol, bisoprolol, metoprolol, atenolol, nebivolol, or carvedilol are effective at controlling heart rate in people with acute atrial fibrillation who are haemodynamically stable. However, sotalol may cause arrhythmias at high doses. Clinical context DEFINITION
Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Acute atrial fibrillation includes both the first symptomatic onset of chronic or persistent atrial fibrillation and episodes of paroxysmal atrial fibrillation. It is sometimes difficult to distinguish new-onset atrial fibrillation from previously undiagnosed long-standing atrial fibrillation. By contrast, chronic atrial fibrillation is more sustained and can be described as paroxysmal (with spontaneous termination and sinus rhythm between recurrences), persistent, or permanent atrial fibrillation. This review deals with people with acute and recent-onset atrial fibrillation who are haemodynamically stable. The consensus is that people who are not haemodynamically stable should be treated with immediate direct current cardioversion. We have excluded studies in people with atrial fibrillation arising during or soon after cardiac surgery. Diagnosis Acute atrial fibrillation should be suspected in people presenting with dizziness, syncope, dyspnoea, or palpitations. Moreover, atrial fibrillation can contribute to a large number of other non-specific symptoms. Palpation of an irregular pulse is generally only considered sufficient to raise suspicion of atrial fibrillation; diagnosis requires confirmation with ECG. However, in those with paroxysmal atrial fibrillation, ambulatory monitoring [1] [2] may be required.
INCIDENCE/ PREVALENCE
We found limited evidence on the incidence or prevalence of acute atrial fibrillation. Extrapolation from the Framingham study suggests an incidence in men of 3/1000 person-years at age 55 years, [3] rising to 38/1000 person-years at age 94 years. In women, the incidence was 2/1000 personyears at age 55 years and 32.5/1000 person-years at age 94 years. The prevalence of atrial fibrillation ranged from 0.5% for people aged 50 to 59 years to 9% in people aged 80 to 89 years. Among acute emergency medical admissions in the UK, 3% to 6% had atrial fibrillation, and about [4] [5] 40% of these were newly diagnosed. Among acute hospital admissions in New Zealand, [6] 10% (95% CI 9% to 12%) had documented atrial fibrillation.
AETIOLOGY/ Common precipitants of acute atrial fibrillation are acute MI and the acute effects of alcohol. Age RISK FACTORS increases the risk of developing acute atrial fibrillation. Men are more likely than women to develop atrial fibrillation (38 years' follow-up from the Framingham Study; RR, after adjustment for age and [7] known predisposing conditions, 1.5). Atrial fibrillation can occur in association with underlying disease (both cardiac and non-cardiac) or can arise in the absence of any other condition. Epidemiological surveys found that risk factors for the development of acute atrial fibrillation include ischaemic heart disease, hypertension, heart failure, valve disease, diabetes, alcohol abuse, thyroid [3] disorders, and disorders of the lung and pleura. In a British survey of acute hospital admissions of people with atrial fibrillation, a history of ischaemic heart disease was present in 33%, heart © BMJ Publishing Group Ltd 2014. All rights reserved.
........................................................... 2
Cardiovascular disorders
Atrial fibrillation (acute onset)
[5]
failure in 24%, hypertension in 26%, and rheumatic heart disease in 7%. In some populations, the acute effects of alcohol explain a large proportion of the incidence of acute atrial fibrillation. [8] Paroxysms of atrial fibrillation are more common in athletes. PROGNOSIS
Spontaneous reversion: observational studies and placebo arms of RCTs found that more than 50% of people with acute atrial fibrillation revert spontaneously within 24 to 48 hours, especially if atrial fibrillation is associated with an identifiable precipitant such as alcohol or MI. Progression to chronic atrial fibrillation: we found no evidence about the proportion of people with acute atrial fibrillation who develop more chronic forms of atrial fibrillation (e.g., paroxysmal, persistent, or permanent atrial fibrillation). Mortality: we found little evidence about the effects on mortality of acute atrial fibrillation where no underlying cause is found. Acute atrial fibrillation during MI is an [9] independent predictor of both short- and long-term mortality. Heart failure: onset of atrial fibril[10] lation reduces cardiac output by 10% to 20%, irrespective of the underlying ventricular rate, [11] and can contribute to heart failure. People with acute atrial fibrillation who present with heart failure have worse prognoses. Stroke: acute atrial fibrillation is associated with a risk of imminent [12] [13] [14] [15] stroke. One case series using transoesophageal echocardiography in people who had developed acute atrial fibrillation within the preceding 48 hours found that 15% had atrial [16] thrombi. An ischaemic stroke associated with atrial fibrillation is more likely to be fatal, have a recurrence, or leave a serious functional deficit among survivors than a stroke not associated with [17] atrial fibrillation.
AIMS OF To reduce symptoms, morbidity, and mortality with minimum adverse effects. INTERVENTION OUTCOMES
Major outcomes include: thromboembolism, stroke or transient ischaemic attack, major bleeding, mortality, and adverse effects of treatment. Proxy measures include heart rhythm, ventricular rate, and time to restoration of sinus rhythm. The following outcomes are reported in this review: for the question on interventions to prevent embolism: thromboembolic events (thromboembolism, stroke, TIA); for the question on interventions for conversion to sinus rhythm: conversion to sinus rhythm; for the question on interventions to control heart rate: control of heart rate; for all questions: mortality, adverse effects. Frequent spontaneous reversion to sinus rhythm makes it difficult to interpret short-term studies of rhythm; treatments may accelerate restoration of sinus rhythm without increasing the proportion of people who eventually convert. The clinical importance of changes in mean heart rate is also unclear.
METHODS
Clinical Evidence search April 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2014, Embase 1980 to April 2014, and The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts of the studies retrieved from the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing at least 20 individuals (at least 10 per arm), of whom at least 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were studied, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table, p 42 ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
© BMJ Publishing Group Ltd 2014. All rights reserved.
...........................................................
3
Cardiovascular disorders
Atrial fibrillation (acute onset)
QUESTION
What are the effects of interventions to prevent embolism in people with recent-onset atrial fibrillation who are haemodynamically stable?
OPTION
ANTITHROMBOTIC TREATMENT BEFORE CARDIOVERSION. . . . . . . . . . . . . . . . . . . . . . . . .
•
For GRADE evaluation of interventions for Atrial fibrillation (acute onset), see table, p 42 .
•
There is consensus that antithrombotic treatment with heparin should be given before cardioversion to reduce risk of embolism in people who are haemodynamically stable, but we found no RCT evidence to show whether this is effective. Benefits and harms
Antithrombotic treatment before cardioversion: We found no systematic review or RCTs on the use of antithrombotic treatment versus placebo before cardioversion in people with acute atrial fibrillation of less than 7 days' duration. Comment:
One RCT compared low molecular weight heparin with unfractionated heparin (155 people with atrial fibrillation of between 2 and 19 days' duration, undergoing a transoesophageal echocardiog[18] raphy-guided cardioversion strategy). The RCT found no significant difference between low molecular weight heparin and unfractionated heparin in rates of thrombus observation, stroke, systemic embolism, or bleeding. However, low molecular weight heparin did allow earlier hospital discharge. Clinical guide: There is consensus to give heparin to people who have cardioversion within 48 hours of the onset of arrhythmia, but we found insufficient evidence from trials to support this. The decision to give anticoagulation both in the short-term and after cardioversion is usually based on [19] an individual's intrinsic risk of thromboembolism. Warfarin is not used as an anticoagulant in acute atrial fibrillation because of its slow onset of action. One transoesophageal echocardiography study in people with a recent embolic event found left atrial thrombus in 15% of people with acute [16] atrial fibrillation of less than 3 days' duration. This would suggest that such people may benefit from formal anticoagulation, or need to be evaluated by transoesophageal echocardiography before cardioversion.
QUESTION
What are the effects of interventions for conversion to sinus rhythm in people with recentonset atrial fibrillation who are haemodynamically stable?
OPTION
FLECAINIDE FOR RHYTHM CONTROL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
•
For GRADE evaluation of interventions for Atrial fibrillation (acute onset), see table, p 42 .
•
Oral or intravenous flecainide increases the likelihood of reversion to sinus rhythm compared with placebo in people with haemodynamically stable acute atrial fibrillation.
•
Flecainide is associated with serious adverse events, such as severe hypotension and torsades de pointes.
•
CAUTION: Flecainide should not be used in people with ischaemic heart disease as it can cause (life-threatening) arrhythmias. Amiodarone should be used in preference to flecainide in people with structural heart disease. Benefits and harms
Flecainide versus placebo: [20] [21] We found five RCTs.
[22]
[23]
[24]
Conversion to sinus rhythm Flecainide compared with placebo Oral or intravenous (iv) flecainide is more effective at increasing the rate of conversion to sinus rhythm at 1 to 24 hours in people with acute atrial fibrillation (moderate-quality evidence).
© BMJ Publishing Group Ltd 2014. All rights reserved.
...........................................................
4
Cardiovascular disorders
Atrial fibrillation (acute onset)
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Rate of conversion to sinus rhythm [20]
RCT 3-armed trial
62 people, aged Conversion to sinus rhythm , >75 years, onset of 8 hours atrial fibrillation 7 20/22 (91%) with oral flecainide days or less 10/21 (48%) with placebo
P 120 beats/minute; systolic blood pressure 90 mmHg or more, without severe heart failure; 108 people with at least 1 underlying condition that may explain [61] atrial arrhythmia; mean age 64 years) compared intravenous (iv) diltiazem with placebo. After randomisation, a dose of iv diltiazem (0.25 mg/kg over 2 minutes), or equivalent placebo, was given. If the first dose had no effect after 15 minutes, then the code was broken and diltiazem 0.35 mg/kg every 2 minutes was given, regardless of randomisation. The RCT found no difference in response rate to diltiazem in people with atrial fibrillation compared with those with atrial flutter. In the diltiazem-treated group, seven people developed asymptomatic hypotension (systolic blood
© BMJ Publishing Group Ltd 2014. All rights reserved.
..........................................................
34
Cardiovascular disorders
Atrial fibrillation (acute onset)
pressure 2
Directness points deducted for wide inclusion criteria and for use of different regimens
What are the effects of interventions to control heart rate in people with recent-onset atrial fibrillation who are haemodynamically stable? © BMJ Publishing Group Ltd 2014. All rights reserved.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cardiovascular disorders
Atrial fibrillation (acute onset)
Important outcomes Studies (Participants) 1 (100)
[43]
2 (333)
[53]
[54]
Control of heart rate, Conversion to sinus rhythm, Mortality Outcome
Comparison
Type of evidence
Quality
Consistency
Directness
Effect size
GRADE
Comment
Control of heart rate
Amiodarone versus digoxin
4
–2
–1
0
0
Very low
Quality points deducted for sparse data and incomplete reporting of results; consistency point deducted for different results at different endpoints
Control of heart rate
Digoxin versus placebo
4
0
0
–1
0
Moderate
Directness point deducted for wide inclusion criteria
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasirandomisation, sparse data [
