Download Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation
Philip J Podrid, MD
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CLASSIFICATION — Atrial fibrillation (AF) is the most common sustained arrhythmia seen by
the physician. Its prevalence in the population increases with age, and it is estimated to affect
over 4 percent of the population above the age of 60 [ 1-3].
The following classification for AF when first detected has been proposed by the American
College of Cardiology/American Heart Association/European Society of Cardiology
(ACC/AHA/ESC) [4].

Paroxysmal (ie, self-terminating) AF in which the episodes of AF generally last 7 days
(usually less than 24 hours) and may be recurrent, which is defined as two or more episodes.

Persistent AF fails to self-terminate and lasts for longer than seven days. Persistent AF
may be paroxysmal if it recurs after reversion.

Permanent AF is considered to be present if the arrhythmia lasts for more than one
year and cardioversion either has not been attempted or has failed. (Permanent AF has also
been called sustained or chronic AF).

"Lone" AF describes paroxysmal, persistent, or permanent AF in individuals without
structural cardiac or pulmonary disease who have a low risk for thromboembolism or mortality.
Lone AF has primarily been applied to patients 60 years of age but older patients also may be
at low risk. (See "Lone and low-risk atrial fibrillation").
This classification applies to episodes of AF that last more than 30 seconds and that are
unrelated to a reversible cause. If the AF is secondary to cardiac surgery, pericarditis,
myocardial infarction (MI), hyperthyroidism, pulmonary embolism, pulmonary disease, or other
reversible causes, therapy is directed toward the underlying disease as well as the AF. ( See
"Causes of atrial fibrillation").
Depending upon the population studied, it has been estimated that 25 to 90 percent of cases
of AF are paroxysmal [5-9]. However, the frequency of paroxysmal AF (PAF) must be
considered uncertain since up to 90 percent of episodes are asymptomatic [ 10,11], including
some that last more than 48 hours [10].
ETIOLOGY — The causes of PAF are identical to those associated with sustained AF, but the
frequency of the underlying conditions is not clear. One factor that contributes to this
uncertainty is that PAF is often equated with lone AF. Lone AF accounts for less than 15 to as
many as 30 percent of cases of permanent (ie, chronic) AF and up to 25 to 45 percent of cases
of paroxysmal AF. (See "Lone and low-risk atrial fibrillation", section on Prevalence).
Among patients with PAF in whom a cause can be identified, the most common are [ 9,12,13]:





Hypertension — 16 to 34 percent
Coronary artery disease — 6 to 24 percent
Rheumatic heart disease — 3 to 14 percent
Hyperthyroidism — 2 percent
Miscellaneous — 12 to 16 percent
(See "Causes of atrial fibrillation").
PATHOGENESIS — The factors that precipitate PAF, particularly in patients without apparent
structural heart disease, are incompletely understood. Atrial premature beats appear to be
most important, as they are in patients with permanent AF. ( See "Causes of atrial fibrillation",
section on Pathogenesis).
Atrial premature beats — Several series in which Holter monitoring was performed have shown
that the majority of episodes of PAF are triggered by atrial premature beats [14-16], while a
small number of PAF episodes are preceded by typical atrial flutter or atrial tachycardia [ 16].
Ectopic foci are most often located near the pulmonary veins, occurring in 89 and 94 percent
of cases in two series [14,15]. Other foci are located in the right and left atrium [15]. The
importance of the pulmonary veins in the genesis of PAF is further illustrated by the beneficial
effect of pulmonary vein isolation. (See "Radiofrequency catheter ablation to prevent recurrent atrial
fibrillation").
Atrial premature beats appear to be most important as a trigger in patients with PAF who have
normal or near-normal hearts. The relative importance of atrial premature beats or other
triggers versus an abnormal substrate is much less clear in patients with significant structural
heart disease. (See "Electrocardiographic and electrophysiologic features of atrial fibrillation").
Autonomic dysfunction — The autonomic nervous system may be involved, as both increased
vagal (parasympathetic) and sympathetic tone can promote the development of AF [ 17]. Vagal
tone is predominant in normal hearts, which may explain why vagally-mediated AF is often
seen in athletic young men without apparent heart disease who have slow heart rates during
rest or sleep; such patients may also have an ECG pattern of common atrial flutter alternating
with AF [17,18].
Vagal innervation of the atria is heterogeneous. As a result, the induction of AF by vagal
stimulation may result from shortening of the atrial refractory period in some areas of the
atrial myocardium, producing heterogeneity of atrial refractoriness [ 19]. Vagal stimulation and
the associated hypotension may also contribute to the development of syncope in association
with episodes of AF [20].
Increased sympathetic tone may be associated with AF occurring in patients with underlying
heart disease and during exercise or other activity [17]. However, AF during exercise is not a
common event; in a retrospective review of 3000 exercise tests, there were only four episodes
of AF [21]. Sympathetic stimulation has also been suggested as the cause for AF associated
with hyperthyroidism and coronary artery bypass graft surgery. ( See "Arrhythmias after cardiac
surgery: Atrial fibrillation and atrial flutter" and see "Cardiovascular effects of hyperthyroidism").
Other — In addition to increased vagal tone and associated bradycardia [ 20], another cause for
syncope in patients with PAF is underlying sick sinus syndrome. In this setting, the abrupt
termination of AF results in a prolonged period of asystole and eventual syncope due to
dysfunction of the sinus node and a variable duration of time before it becomes active. ( See
"Manifestations and causes of the sick sinus syndrome").
Another predictive factor for episodes of PAF is increased P wave duration derived from signal
averaged electrocardiograms (SAECGs) [22-24]. This finding presumably reflects underlying
electrophysiologic abnormalities of the atrial myocardium. ( See "Use of the signal-averaged
electrocardiogram in arrhythmia evaluation and management").
NATURAL HISTORY — The natural history of PAF is unclear, largely because of uncertainty
about its actual incidence. Recurrent episodes of AF are detected in approximately 90 percent
of patients when continuous monitoring techniques are used [ 10]. However, up to 90 percent
of episodes are not recognized by the patient [11] and asymptomatic episodes lasting more
than 48 hours are not uncommon, occurring in 17 percent of patients in a report using
continuous monitoring [10].
Most studies have involved only those patients with symptoms from the arrhythmia, including
palpitations, weakness, dizziness, and dyspnea. However, apparently typical symptoms are not
always related to arrhythmia. This was shown in a continuous monitoring study (permanent
pacemaker with AF detection function and electrogram storage) in which 40 percent of patients
had some episodes of AF-like symptoms in the absence of AF [10].
Recurrence of PAF — The recurrence rate of AF is high in patients who present with PAF. The
incidence in different reports has ranged from 70 percent at one year (without antiarrhythmic
therapy) [25] to 90 percent at four years [26] to 60 to 65 percent at five to six years [5,9,27].
These estimates almost certainly represent an underestimate, since up to 90 percent of
episodes are asymptomatic [10,11], including some that last more than 48 hours; such
prolonged asymptomatic episodes occurred in 17 percent of patients in a report using
continuous monitoring [10]. The latter study also showed that 40 percent of patients had
episodes of AF-like symptoms in the absence of AF [10].
The Stroke Prevention in Atrial Fibrillation (SPAF) trial evaluated 341 patients with intermittent
AF who were followed for 26 months [28]. During this time, 49 percent had recurrent AF
documented on at least one ECG. There were 104 additional patients who underwent
cardioversion (electric or pharmacologic); the recurrence rate during follow-up was 54 percent
in this group.
The report from SPAF also provided insight into clinical and echocardiographic factors that
predict recurrence of AF [28]. When compared to patients without a recurrence of AF, patients
with any AF recurrence were more likely to have heart failure (17 versus 8 percent) or a prior
myocardial infarction (15 versus 5 percent). Echocardiographic factors associated with AF
recurrence included moderate to severe left ventricular dysfunction (12 versus 3 percent in
those without recurrence) and larger left atrial diameter. Compared to a normal left atrial
diameter of less than 4.0 cm, the relative risk of recurrent AF was 1.6 with a left atrial
diameter between 4.1 and 5.0 cm and 4.5 above 5.0 cm.
These risk factors are similar to those for recurrence after cardioversion to sinus rhythm in
patients with permanent AF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with
atrial fibrillation: Recommendations", section on Risk factors for recurrent AF).
Spontaneous reversion — The likelihood of spontaneous reversion of AF to sinus rhythm
clearly relates to the population studied. When ambulatory monitoring is used, up to 90
percent of episodes of PAF are asymptomatic and almost all revert spontaneously [ 10,11].
Among patients with symptomatic new onset AF, the duration of the arrhythmia is a predictor
of spontaneous reversion. This was illustrated in a study that evaluated 1822 patients admitted
to the hospital because of AF; 356 (20 percent) had an arrhythmia duration less than 72 hours
[29]. Among these 356 patients, two-thirds spontaneously reverted to sinus rhythm. The only
predictor of spontaneous reversion was presentation within 24 hours of symptoms (odds ratio
1.8); in comparison, left atrial dimension was similar in those with and without spontaneous
reversion.
Progression to permanent AF — It has been suggested that 5 to 18 percent of patients with
PAF develop permanent or chronic AF; however, follow-up has been variable and progression
increases with time [5,27,28,30,31]. In different reports, the rate of progression to permanent
AF was 8, 12, 18, and 25 percent at one, two, four, and five years, respectively [ 27,28,31].
A number of studies have attempted to identify predictors of progression to permanent AF
[27,28]. In the report from SPAF cited above, the following differences were noted between the
patients with paroxysmal and permanent AF [28]:



Patients with PAF were more likely to have a recent onset of AF — 24 versus 10 percent
with onset less than three months, and 20 versus 11 percent with onset between three and
twelve months.
Patients with PAF were less likely to have hypertension or heart failure.
On echocardiography, patients with PAF had a smaller left atrial diameter (4.3 versus
4.8 cm), were less likely to have a diameter greater than 5.0 cm (11 versus 34 percent), and
were less likely to have moderate to severe left ventricular dysfunction (6 versus 18 percent).
For every 1 cm increase in left ventricular systolic dimension, there was a 1.8 fold greater risk
of developing permanent AF.
The transition from PAF to permanent AF also depends upon the underlying etiology for the
arrhythmia. Progression has been reported in approximately 66 percent of patients with
rheumatic mitral stenosis, 40 percent with hypertension, and 27 percent with ischemic heart
disease [32,33]. On the other hand, as few as 5 percent of patients with paroxysmal lone AF
progress to permanent AF over a six year period [34].
Two other predictors of progression to permanent AF have been identified in individual reports:

Increasing age — The hazard ratio for progression in two reports was 1.41 to 1.82 for
each 10-year increase in age [27,31]

Findings on P-wave triggered SAECG — A P wave duration 145 ms and root mean
square voltage for the last 30 ms <3.0 microV may be associated with a high risk of
progression (43 versus 4 percent in patients without these abnormalities at 26 months in a
prospective study of 122 consecutive patients with PAF) [35]. (See "Use of the signal-averaged
electrocardiogram in arrhythmia evaluation and management").
Risk of embolization — While the risk of embolization is well established in chronic or
permanent AF, there has been controversy concerning the risk in patients with documented
PAF. A number of studies noted a lower risk in patients with PAF compared to those with
permanent AF [33,36]. In the Framingham Heart Study, for example, the annual incidence of
stroke in patients with PAF was 1.3 percent [33].
In contrast to these data, several large trials have reported no difference in the risk of stroke
between those with PAF and permanent AF [37-39].

Among patients not on anticoagulation in SPAF, the yearly stroke rate was the same in
PAF and permanent (or sustained) AF (5.6 versus 5.9 percent with no aspirin and 3.2 versus
3.3 percent on aspirin) in the different risk groups (show figure 1) [37]. Among the 24 percent
of patients with PAF predicted to be at high risk, the rate of ischemic stroke was 7.8 percent
per year.

The Boston Area Anticoagulation Trial in Atrial Fibrillation (BAATAF) found a similar
incidence of stroke in the two groups (13 versus 17 percent) for a yearly incidence of 2.5
percent and 2.8 percent, respectively [38].
A similar lack of difference in embolic risk was noted in a pooled analysis from the five
randomized control trials of anticoagulation in AF [39]. Furthermore, a subset meta-analysis
found that the reduction in ischemic stroke with oral anticoagulation in patients with PAF (1.5
versus 4.7 events per 100 patient-years, hazard ratio 0.32) was similar to that in patients with
permanent AF [40].
One concern is that these trials were not designed to specifically evaluate patients with PAF,
who constituted approximately 12 percent of the patients. There were also problems with the
definition of PAF as well as documentation of the frequency and duration of AF. Embolic events
can occur in patients with acute AF for as little as 72 hours [ 41].
Additional evidence of the embolic risk associated with PAF comes from AFFIRM and RACE
trials that compared rhythm to rate control in patients with paroxysmal or permanent AF
[42,43]. Embolization occurred with equal frequency whether a rhythm control or a rate control
strategy was adopted, although there was a nonsignificant trend toward more embolic events
with rhythm control which could have reflected, in part, a high rate of crossover from rhythm
to rate control (17 and 38 percent at one and five years, respectively, in AFFIRM) [42]. In both
groups, embolization primarily occurred after warfarin had been stopped or when the INR was
subtherapeutic. (See "Rhythm control versus rate control in atrial fibrillation").
Paroxysmal AF also may be a cause of cryptogenic stroke or transient ischemic attack. The
frequency with which this might occur was illustrated in a report of 28 such patients [44]. A
long-term automatic event recorder showed one or more episodes of PAF in four. Furthermore,
eight of the 32 other patients in this series presented with PAF, which was considered the
cause of the stroke.
There are at least two reasons for the risk of embolization even when sinus rhythm appears to
be maintained:


Recurrent episodes of paroxysmal AF are common and most often asymptomatic
[10,11]
Some patients have other reasons for embolic risk such as complex aortic plaque or left
ventricular systolic dysfunction. (See "Indications for anticoagulation in heart failure" and see
"Embolism from aortic plaque: Thromboembolism").
Although periods of sinus rhythm should reduce stroke risk, this may be counterbalanced by
an increase in risk during the transition from AF to sinus rhythm as occurs after cardioversion.
(See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation").
As in permanent AF, increasing age, hypertension, and prior stroke best correlate with stroke
probability in PAF. In the SPAF trial of 460 patients with PAF treated with aspirin, the stroke
rate was highest (7.8 percent per year) in the 24 percent of patients with PAF who met criteria
for being at high risk (show figure 1) [37].
A separate issue is the rate of embolization during and after cardioversion in patients with AF
of less than 48 hours duration. The risk of cardioversion-associated embolization is very low in
such patients, even without warfarin (four episodes among 573 patients in two series) [45,46].
(See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on AF
of less than 48 hours duration).
MANAGEMENT OF THE ARRHYTHMIA — Management of the patient with transient or persistent
paroxysmal AF involves several aspects and consideration of the presence or absence of
symptoms during episodes and of underlying heart disease. Both acute management of the
arrhythmia and long-term therapy must be considered.
The following approach is generally in agreement with guidelines published in 2006 by the
American College of Cardiology/American Heart Association/European Society of Cardiology
(ACC/AHA/ESC) [4].
Acute therapy — The are two components to the acute therapy of PAF:

Acute control of the heart rate, usually with a beta blocker or calcium channel blocker
(verapamil or diltiazem) or, if the patient has heart failure or hypotension, digoxin (show table 1).
(See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy").

Unless PAF reverts spontaneously, electrical cardioversion in patients who are
hemodynamically unstable and either electrical or pharmacologic cardioversion in patients who
are hemodynamically stable but have unacceptable symptoms and in patients with a firstdetected episode of AF (show table 2A-2C) [4]. Electrical cardioversion is usually preferred, since
pharmacologic cardioversion is less often successful and may be associated with a greater risk
of proarrhythmia. (See "Restoration of sinus rhythm in atrial fibrillation: Recommendations").
Prevention of recurrence — Patients with frequent or highly symptomatic PAF may require
pharmacologic or nonpharmacologic therapy to prevent recurrence. The general principles of
antiarrhythmic drug therapy in PAF are similar to those for the maintenance of sinus rhythm
after cardioversion in patients with persistent AF. The choice of drug is often determined by
the clinical setting (show algorithm 1). (See "Antiarrhythmic drugs to maintain sinus rhythm in
patients with atrial fibrillation: Recommendations").
There is increasing evidence that amiodarone is significantly more effective for maintenance of
sinus rhythm than other antiarrhythmic drugs. In the randomized Canadian Trial of Atrial
Fibrillation (in which most patients had PAF) and a substudy analysis from the rhythm control
arm in AFFIRM, patients treated with amiodarone had a greater likelihood of being free from
recurrent AF at 12 to 16 months than those treated with sotalol (60 to 65 versus 37 to 38
percent) or class I antiarrhythmic drugs (62 to 65 versus 23 to 37 percent) ( show figure 2)
[47,48]. The ACC/AHA/ESC guidelines concluded that, because of concern about side effects,
amiodarone should be used cautiously as first-line therapy in patients without heart failure [4].
(See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation:
Recommendations", section on Relative efficacy).
Nonpharmacologic therapies are an increasingly used option in patients with PAF. These
include modalities such as radiofrequency ablation (eg, pulmonary vein/left atrial isolation) and
the maze procedure in an attempt to prevent recurrent AF. ( See "Radiofrequency catheter ablation
to prevent recurrent atrial fibrillation" and see "Surgical approaches to prevent recurrent atrial
fibrillation").
Rate control — Rate control with a beta blocker, verapamil, or diltiazem is not generally needed
in PAF. However, such drugs may be considered in patients with highly symptomatic episodes
and can be used for an acute episode. Some patients are maintained on one of these drugs to
control the ventricular rate when PAF occurs. (See "Control of ventricular rate in atrial fibrillation:
Pharmacologic therapy").
Digoxin is a second-line therapy for rate control except in patients with heart failure. There are
conflicting data as to whether digoxin slows the heart and minimizes symptoms during
episodes in patients with PAF [49,50].
Some patients continue to have inadequate rate control with severe symptomatic episodes
despite pharmacologic therapy. Such patients may benefit from AV nodal ablation and
pacemaker therapy [51]. (See "Control of ventricular rate in atrial fibrillation: Nonpharmacologic
therapy").
ANTICOAGULATION — As a group, patients with PAF have a risk for embolic events that
appears to be similar to that in patients with permanent AF (show figure 1) [37-40,52]. (See "Risk
of embolization" above). There are two issues related to anticoagulation therapy that are
discussed in detail separately, but will be briefly reviewed here: anticoagulation related to
cardioversion; and chronic anticoagulation.
Prior to and after cardioversion — Among patients undergoing electrical or pharmacologic
cardioversion, anticoagulation is typically given both before and after cardioversion. Because of
the risk from possible preexisting thrombi, most patients should receive three to four weeks of
oral anticoagulation with warfarin prior to cardioversion [4,52]. Shorter term anticoagulation
(eg, heparin at presentation) can be given before cardioversion if screening TEE shows no
thrombi or if the AF is known to be present for less than 48 hours in the absence of underlying
structural heart disease (show table 3); both of these groups have a very low rate of
cardioversion-associated embolization [45,46,52]. (See "Anticoagulation prior to and after
restoration of sinus rhythm in atrial fibrillation").
Chronic therapy — There are no randomized trials that have specifically evaluated the role of
chronic anticoagulation in patients with PAF. However, these patients are at risk for embolism
(show figure 1) [37-40] and a benefit of chronic oral anticoagulation was suggested in a metaanalysis of trials of nonvalvular AF: the reduction in ischemic stroke with oral anticoagulation
therapy in patients with PAF (1.5 versus 4.7 events per 100 patient-years, hazard ratio 0.32)
was similar to that in patients with permanent AF [40].
These observations support the recommendation by the 2004 ACCP Consensus Conference
that patients with frequent or prolonged episodes should be treated as if they have permanent
AF [52]. The choice of therapy (warfarin versus aspirin) varies with the estimated stroke risk.
Although a number of risk stratification models are available for patients with permanent AF,
we believe the CHADS2 score is currently the best validated and most clinically useful ( show
table 4) [53-55]. (See "Anticoagulation to prevent embolization in atrial fibrillation", section on Patient
selection)

Patients with a CHADS2 score of 0 are at low risk for ischemic stroke or peripheral
embolization (0.5 percent per year in the absence of warfarin) and can be managed with
aspirin.

Patients with a CHADS2 score 3 are at high risk (5.3 to 6.9 percent per year) and
should, in the absence of a contraindication, be treated with warfarin.

Patients with a CHADS2 score of 1 or 2 are at intermediate risk (1.5 to 2.5 percent per
year). One exception is that most experts would consider patients with a prior ischemic stroke,
transient ischemic attack, or systemic embolic event to be at high risk even if they have no
other risk factors and therefore a CHADS2 score of 2. Furthermore, the great majority of these
patients have some other risk factor and a CHADS2 score of at least 3.
Among patients at intermediate risk, the choice between warfarin therapy and aspirin will
depend upon many factors, including patient preference. Another potential consideration is the
frequency and duration of episodes of AF. Among patients with very infrequent and short
episodes, any protective effect from anticoagulation may be more than offset by bleeding risk
and inconvenience. However, there is at present no good way to confidently identify these
patients.
It may be helpful to consider the definition of paroxysmal AF in the SPAF trial, which provided
the best data on the equivalence of stroke risk in paroxysmal (intermittent) and chronic
(permanent) AF (show figure 1) [37]. AF was considered paroxysmal if, within three to twelve
months of study entry, sinus rhythm was documented on an ECG, there were at least two
documented episodes of AF on ECG, and there was no reversible cause of AF (eg,
hyperthyroidism, pneumonia). However the stroke risk for brief episodes of PAF is still not
certain since duration of a paroxysm or the frequency of arrhythmic events in this trial are not
known.
PACEMAKERS — Pacemaker insertion may be warranted in selected patients with AF, including
PAF. Examples include:

Patients with sick sinus syndrome. (See "Treatment of the sick sinus syndrome").

Selected patients with heart failure or left ventricular dysfunction. ( See "Cardiac
resynchronization therapy (biventricular pacing) in heart failure" and see "Overview of cardiac pacing in
heart failure").

Patients who undergo AV nodal ablation for rate control. ( See "Rate control" above and
see "Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy").
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GRAPHICS
Stroke rates AF risk category
Rate of ischemic stroke is related to risk category
The incidence of a stroke in patients with either intermittent or sustained atrial fibrillation (AF)
is related to risk category; the patients were treated with aspirin and followed for a mean of
two years. Among those with intermittent AF, 24 percent were high risk, 32 percent are
moderate risk and 43 percent are low risk; among those with sustaind AF, the respective
values were 30, 34, and 36 percent. The stroke risk was similar in patients with intermittent
and sustained AF.
High risk: any of the following - age >75 and hypertension, age >75 and female, systolic BP
>160 mmHg, prior stroke or transient ischemic attack; Moderate risk: either of - hypertension
and age 75 or diabetes and no high risk features; Low risk: no moderate or high risk
features.
Data from Hart, RG, Pearce, LA, Rothbart, RM, et al, J Am Coll Cardiol 2000; 35:183.
ACC AHA ESC rate control of AF
ACC/AHA/ESC guideline summary: Pharmacologic rate control during atrial
fibrillation (AF)
Class I - There is evidence and/or general agreement that the following approaches
are effective for rate control in patients with AF
The heart rate should be measured at rest and during exercise, particularly in patients with
symptoms related to AF with exertion.
An oral beta blocker or nondihydropyridine calcium channel blocker in most patients with
persistent or permanent AF.
Oral digoxin in patients with heart failure or asymptomatic left ventricular dysfunction and in
patients who are sedentary.
Intravenous therapy in the following acute settings in the absence of preexcitation:
1. Intravenous beta blockers or nondihydropyridine calcium channel blocker, with caution in patients
with hypotension or heart failure.
2. Intravenous digoxin or amiodarone in patients with heart failure.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the
following approaches in patients with AF
If monotherapy is ineffective, digoxin plus a beta blocker or nondihydropyridine calcium channel
blocker.
When medical therapy is ineffective or not tolerated, ablation of the atrioventricular (AV) node or
accessory pathway.
Intravenous therapy in the following acute settings:
1. Intravenous amiodarone when the intravenous drugs cited above are ineffective or
contraindicated.
2. Intravenous procainamide or ibutilide in patients with an accessory pathway in whom electrical
cardioversion is not necessary.
Class IIb - The weight of evidence or opinion is less well established for the
usefulness of the following approaches in patients with AF
Oral amiodarone when combination therapy with beta blockers, nondihydropyridine calcium
channel blockers, and/or digoxin do not adequately control the ventricular rate at rest and during
exercise.
Intravenous procainamide, disopyramide, ibutilide, or amiodarone with conduction over an
accessory pathway in stable patients.
Catheter ablation of the AV node when the ventricular rate cannot be controlled with the above
oral drugs or tachycardia-induced cardiomyopathy is suspected.
Class III - There is evidence and/or general agreement that the following
approaches are not useful or may be harmful in patients with AF
Oral digoxin as the sole drug in paroxysmal AF.
Catheter ablation of the AV node as a first-line therapy.
Intravenous nondihydropyridine calcium channel blocker may worsen decompensated heart
failure.
Because they may paradoxically increase the ventricular rate, intravenous digoxin or
nondihydropyridine calcium channel blocker in patients with a preexcitation syndrome.
Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001
guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;
48:e149.
Electrical cardioversion AF
ACC/AHA/ESC guideline summary: Direct-current (DC) cardioversion of atrial
fibrillation (AF) and flutter (AFl)
Class I - There is evidence and/or general agreement that immediate R-wave
synchronized DC cardioversion of AF or AFl is indicated in the following settings
AF with a rapid ventricular response that does not respond promptly to pharmacologic measures
and there is evidence of ongoing myocardial ischemia, symptomatic hypotension, angina, or heart
failure.
Preexcitation in the presence of very rapid tachycardia or hemodynamic instability.
Unacceptable symptoms in the absence of hemodynamic instability. Repeated direct current
cardioversion attempts may be made following administration of antiarrhythmic drugs for early
relapse. In this category, immediate cardioversion may not be necessary.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of DC
cardioversion of AF or AFl for patients in the following settings
Part of a long term management strategy.
If the patient prefers, management of symptomatic or recurrent AF if used infrequently.
Class III - There is evidence and/or general agreement that DC cardioversion of AF
or AFl is not useful or may be harmful to patients in the following settings and should
therefore be avoided
Frequent repetition of direct current cardioversion for repeated relapses of AF after short periods
of sinus rhythm in patients who have received procedures despite prophylactic antiarrhythmic drug
treatment.
Digitalis toxicity or hypokalemia, settings in which DC cardioversion is contraindicated.
Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001
guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;
48:e149.
Pharmacologic cardioversion AF
ACC/AHA/ESC guideline summary: Pharmacologic cardioversion of atrial
fibrillation (AF)
Class I - There is evidence and/or general agreement that the following drugs are
effective for cardioversion of AF
Flecainide.
Dofetilide.
Propafenone.
Ibutilide.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the
following drugs for cardioversion of AF
Amiodarone, including use as an out-patient when rapid restoration of sinus rhythm does not
appear to be necessary.
A single oral bolus ("pill-in-the-pocket") of propafenone or flecainide in the out-patient
setting in selected patients in whom the safety and efficacy of this approach has been
demonstrated in hospital and who meet the following criteria:
1. The absence of sinus and atrioventricular (AV) node dysfunction, bundle branch block, QT interval
prolongation, Brugada syndrome, and structural heart disease.
2. The presence of AV nodal blockade with a beta blocker or nondihydropyridine calcium channel
blocker to prevent rapid AV conduction if atrial flutter occurs.
Class IIb - The weight of evidence or opinion is less well established for the
usefulness of the following drugs for cardioversion of AF
Quinidine.
Procainamide.
Class III - There is evidence and/or general agreement that the following drugs for
cardioversion of AF are not useful or may be harmful
Digoxin.
Sotalol.
For out-of-hospital cardioversion, quinidine, procainamide, disopyramide, and dofetilide.
Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001
guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;
48:e149.
ACC AHA ESC doses conversion AF
ACC/AHA/ESC guideline summary: Recommended doses of drugs (listed
alphabetically) proven effective for pharmacological cardioversion of atrial
fibrillation
Drug
Route of
administration
Dosage
Potential adverse effects
Inpatient: 1.2 to 1.8 g per day in divided
dose until 10 g total, then 200 to 400
mg/kg as single dose
Oral
Outpatient 600 to 800 mg/day divided
Hypotension, bradycardia, QT
dose until 10 g total, then 200 to 400 mg prolongation, torsade de
per day maintenance
pointes (rare), GI upset,
Amiodarone
Intravenous
(IV)/oral
5 to 7 mg/kg over 30 to 60 min,
constipation, phlebitis (IV use)
then 1.2 to 1.8 g per day continuous
IV or in divided oral doses until 10 g
total, then 200 to 400 mg per day
maintenance
Creatinine clearance (mL/min):
Greater than 60: 500 mcg BID
Dofetilide
Oral
40 to 60: 250 mcg BID
QT prolongation, torsade de
pointes; adjust dose for renal
function, body size, and age
20 to 40: 125 mcg BID
Less than 20: Contraindicated
Oral
Flecainide
Ibutilide
Intravenous
Intravenous
Oral
Propafenone
Quinidine
Intravenous
Oral
200 to 300 mg
1.5 to 3.0 m per kg over 10 to 20
min
1 mg over 10 min; repeat 1 mg
when necessary
450 to 600 mg
1.5 to 2.0 mg per kg over 10 to 20
min
0.75 to 1.5 g in divided doses over 6
to 12 h, usually with a rate-slowing
drug
Hypotension, rapidly
conducting atrial flutter
QT prolongation, torsade de
pointes
Hypotension, rapidly
conducting atrial flutter
QT prolongation, torsade de
pointes, gastrointestinal upset,
hypotension
Dosages given in the table may differ from those recommended by the manufacturers.
Insufficient data are available on which to base specific recommendations for the use of one
loading regimen over another for patients with ischemic heart disease or impaired left
ventricular function, and these drugs should be used cautiously or not at all in such patients.
Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. J Am Coll Cardiol 2006; 48:e149.
ACC AHA ESC maintain NSR AF
ACC/AHA/ESC guideline summary: Antiarrhythmic drug therapy to maintain
sinus rhythm in patients with recurrent paroxysmal or persistent atrial
fibrillation*
Caveats
Flecainide - AVOID in patients with coronary artery disease
Propafenone - AVOID in patients with coronary artery disease; caution if hepatic impairment
or if there has been intermittent atrial flutter
Sotalol - reduce dose (or avoid) in renal impairment; caution with history of bradycardia;
correct hypokalemia before use
Disopyramide - avoid if prostatic symptoms present and reduce dose (or avoid) for renal
impairment
Dofetilide - Reduce dose (or avoid) in renal impairment; correct hypokalemia before use
Amiodarone - consider long-term toxicity; use cautiously in bradycardia or with serious
pulmonary disease
Quinidine and procainamide - not usually used for long-term therapy because of noncardiac
side effects
* Within each box, the antiarrhythmic drugs are listed alphabetically. The vertical flow
represents the order of preference for each condition.
From Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management
of patients with atrial fibrillation. A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines and the European Society of Cardiology
Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the
management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
Recurrent AF amiodarone
The rate of recurrent atrial fibrillation is lowest with amiodarone
The Canadian Trial of Atrial Fibrillation randomized 403 patients with at least one episode of
atrial fibrillation (AF) during the prior six months to low-dose amiodarone, propafenone, or
sotalol. After a mean follow-up of 16 months, the likelihood of being free from recurrent AF
was highest with amiodarone (65 versus 37 percent for sotalol and propafenone) and the
median time to recurrence was longer (>468 versus 98 days). Data from Roy, D, Talajic, M,
Dorian, P, et al. N Engl J Med 2000; 342:913.
ACC AHA ESC anticoag cardiovert
ACC/AHA/ESC guideline summary: Prevention of thromboembolism in patients
with atrial fibrillation (AF) undergoing cardioversion
Class I - There is evidence and/or general agreement that the following approaches
are effective for the prevention of thromboembolism in patients with AF undergoing
cardioversion
For AF duration of 48 hours or duration unknown, anticoagulation with a goal INR of 2.0 to 3.0
for at least three weeks before and four weeks after either electrical or pharmacologic
cardioversion.
For AF duration of more than 48 hours that requires immediate cardioversion due to
hemodynamic instability:
1. Unfractionated heparin should be given concurrently (unless contraindicated) by an initial
intravenous bolus followed by a continuous infusion at a dose adjusted to prolong the activated
partial thromboplastin time to 1.5 to 2.0 times control.
2. Thereafter, oral anticoagulation with a goal INR of 2.0 to 3.0 for at least four weeks as in patients
undergo elective cardioversion.
3. Limited data support the use of subcutaneous low molecular weight heparin.
For AF duration less than 48 hours associated with hemodynamic instability (as manifested by
angina, myocardial infarction, shock, or pulmonary edema), immediate cardioversion should be
performed with delay for prior initiation of anticoagulation.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the
following approaches for the prevention of thromboembolism in patients with AF
undergoing cardioversion
During the 48 hours after the onset of AF, the need for anticoagulation before and after
cardioversion may be based upon the patient's estimated risk of thromboembolism.
A reasonable alternative to anticoagulation prior to cardioversion is transesophageal
echocardiography to look for thrombus in the left atrium or left atrial appendage:
1. If thrombus is not identified, cardioversion is reasonable after initiation of unfractionated heparin
(intravenous bolus followed by infusion at a dose adjusted to prolong the activated partial
thromboplastin time to 1.5 to 2.0 times control).
Limited data support the use of subcutaneous low molecular weight heparin for this indication.
Heparin therapy is continued until oral anticoagulation with warfarin or other vitamin K
antagonist has led to an INR 2.0.
Oral anticoagulation with a goal INR of 2.0 to 3.0 is continued for a total duration of
anticoagulation of at least four weeks.
2. If thrombus is present, oral anticoagulation with a goal INR of 2.0 to 3.0 for at least three weeks
before and four weeks after restoration of sinus rhythm; a longer duration of anticoagulation may be
appropriate even if cardioversion is successful, because the risk of thromboembolism often remains
elevated.
For patients with atrial flutter undergoing cardioversion, anticoagulation according to the
recommendations for AF.
Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001
guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;
48:e149.
CHADS2 score stroke risk AF
CHADS2 score, thromboembolic risk, and effect of warfarin in 11,526 patients
with nonvalvular atrial fibrillation and no contraindications to warfarin therapy
Clinical parameter
Points
Congestive heart failure (any history)
1
Hypertension (prior history)
1
Age 75
1
Diabetes mellitus
1
Secondary prevention in patients with a prior ischemic stroke or a transient ischemic attack;
2
most experts also include patients with a systemic embolic event
Event-rate, percent per year*
CHADS2 score
Warfarin
0
1
2
3
4
5 or 6
0.25
0.72
1.27
2.20
2.35
4.60
No warfarin
0.49
1.52
2.50
5.27
6.02
6.88
NNT
417
125
81
33
27
44
NNT: number needed to treat to prevent one stroke per year with warfarin.
* The CHADS2 score estimates the risk of stroke, which is defined as focal neurologic signs or
symptoms that persist for more than 24 hours and that cannot be explained by hemorrhage,
trauma, or other factors, or peripheral embolization, which is much less common. Transient
ischemic attacks are not included. All differences between warfarin and no warfarin groups are
statistically significant except for a trend with a CHADS2 score of 0. Patients are considered to
be at low risk with a score of 0, at intermediate risk with a score of 1 or 2, and at high risk
with a score 3. One exception is that most experts would consider patients with a prior
ischemic stroke, transient ischemic attack, or systemic embolic event to be at high risk even if
they had no other risk factors and therefore a score of 2. However, the great majority of these
patients have some other risk factor and a score of at least 3.
Data from Go, AS, Hylek, EM, Chang, Y, et al, JAMA 2003; 290:2685; and CHADS2 score from
Gage, BF, Waterman, AD, Shannon, W, JAMA 2001; 285:2864.