CLINICAL FOCUS

358

Clinical Pharmacist

November 2010

Vol 2

Treatment of atrial fibrillation usually involves controlling ventricular rate or restoring sinus rhythm.
Equally important is thromboembolic risk assessment and prescription of an anticoagulant if required

Atrial fibrillation
management
By Helen Williams, PGDip Cardiol, MRPharmS

raditionally, the goal of atrial fibrillation (AF)

management has been to restore sinus rhythm (SR).
This strategy, known as rhythm control or
cardioversion, can be achieved either electrically or
pharmacologically. It is also important to control the
ventricular rate (rate control) to minimise haemodynamic
instability, which can be a consequence of AF. Moreover,
preventing thromboembolism thereby reducing the risk
of stroke or other systemic emboli for patients with AF
is as important as managing the arrhythmia itself.
Following careful assessment of a patient with AF,
management can include a combination of one or more of
these goals. The strategy chosen will depend primarily on
the severity of symptoms and the characteristics of the AF.
In addition, it is essential to address any underlying
causative factors (for example, high blood pressure, heart
failure or hyperthyroidism).

Acute or recent-onset AF
Patients who present with recent-onset AF, defined as
onset in the past 48 hours, and associated haemodynamic
compromise (such as symptomatic hypotension, acute
heart failure, unstable angina, loss of consciousness or
shock) require urgent intervention.
For these patients, the usual aim is to revert them to SR
using electrical direct current (DC) cardioversion. DC
cardioversion involves the application of a controlled
electric shock across the chest wall to override the
disordered conduction and allow the sinus node to regain
control of heart rate. Patients undergoing urgent DC
cardioversion should be treated with heparin before the
procedure and be fully anticoagulated after it.
For patients who are haemodynamically stable,
pharmacological cardioversion can be attempted with
drugs such as flecainide, amiodarone or propafenone.
Recently published guidance from the European Society
of Cardiology summarises the options for acute
management of atrial fibrillation (see Figure 1, p359).1
According to the ESC, drug choice for pharmacological
cardioversion depends on the presence or absence of

Helen Williams is consultant pharmacist for

cardiovascular disease in South London.
E: helen.williams11@nhs.net

SUMMARY
Treatment of atrial fibrillation involves restoring sinus rhythm or controlling
the ventricular rate (or both). The treatment strategy chosen will depend
on the nature of the AF (eg, paroxysmal or persistent) and patient
comorbidities (such as structural heart disease). Rhythm control can be
achieved using antiarrhythmic medicines or electrical cardioversion. Betablockers or calcium channel blockers are first-line options for rate control.
Patients must also be assessed for their risk of stroke. This is usually
done using the CHADS2 score. This scoring system balances the risk of
stroke against the risk of bleeding with anticoagulation and helps
clinicians decide which patients should be anticoagulated.

RESTORATION AND
MAINTENANCE OF
SINUS RHYTHM
IMPROVES
EXERCISE
TOLERANCE,
PROTECTS AGAINST
CARDIOMYOPATHY
AND RELIEVES
SYMPTOMS

structural heart disease. Structural heart disease can include

left-ventricular hypertrophy, bundle branch block,
cardiomyopathy or ischaemia. If structural heart disease is
present, intravenous amiodarone is the medicine of choice; if
it is absent, flecainide is preferred.1 However, National
Institute for Health and Clinical Excellence guidance
published in 2006 recommends that intravenous amiodarone
be used for patients with or without structural heart disease.2
If early electrical or pharmacological cardioversion is
being considered it is essential to exclude the presence of

This is one of two CLINICAL FOCUS

articles in this issue of Clinical
Pharmacist that are linked to a
Centre for Pharmacy Postgraduate
Education learning@lunch flex module on atrial
fibrillation designed for hospital pharmacists
and technicians in England.
You can use these articles to provide key
background knowledge on the topic before
participating in a learning@lunch flex session at
your hospital. The module contains reflective
questions, case studies and practice activities
to allow you to put your learning into action.
You can order copies of this module via your
CPPE key contact at the hospital or by emailing
Jayne Plant on jayne@cppe.ac.uk. Find out
more at www.cppe.ac.uk/learning@lunch.

Vol 2

Persistent and permanent AF

Patients with recurrent or ongoing AF should be assessed
and an appropriate strategy of rhythm or rate control
determined.2
Restoration and maintenance of SR improves exercise
tolerance and cardiac output, protects against the
development of cardiomyopathy and relieves symptoms.
Attaining SR offers the theoretical advantages of
reducing the risk of thromboembolism and, therefore,
the need for chronic anticoagulation, although the
results of the AFFIRM study of rhythm control versus
rate control challenge this assumption.3 AFFIRM found
no difference in all-cause mortality (primary outcome)
or stroke rate between patients assigned to one strategy
or the other.

Rhythm control Rhythm-control strategies aim to restore

and maintain SR. NICE guidance recommends rhythm
control for patients with persistent AF who:2

Are symptomatic
Are under 65 years of age
Present with AF for the first time (ie, lone AF)
Present with AF secondary to a precipitating factor
(that has been treated or corrected)
Have congestive heart failure
For patients with persistent AF, this is usually achieved
by elective DC cardioversion. At first attempt, DC
cardioversion is successful in up to 80% of patients, but
relapse rates are high: 6075% of patients relapse, often
within the first month.4
Patients undergoing elective cardioversion must be
anticoagulated for at least four weeks before, and
following, the procedure to reduce the risk of systemic
thromboemboli.1
If DC cardioversion fails, an antiarrhythmic medicine
(such as amiodarone or sotalol) administered for four
weeks before the procedure is repeated can improve
efficacy. If patients relapse, long-term antiarrhythmic
therapy may be required to maintain SR following DC
cardioversion. In these circumstances, a beta-blocker is
used first line to slow conduction and prevent
tachycardias that can precipitate reversion to AF.
If a beta-blocker is ineffective, contraindicated or not
tolerated, second-line options are:2
Amiodarone in the presence of structural heart
disease
Flecainide or sotalol in the absence of structural
heart disease

ranges from 60 to 80 beats/min at rest and between 90 and

115 beats/min during moderate exercise, although this
varies depending on patient age.1
Rate-control strategies are recommended by NICE for
patients with persistent AF who:2

Are over 65 years of age

Have coronary artery disease
Have contraindications to antiarrhythmic medicines
Are unsuitable for cardioversion

Rate control is also recommended for patients with

permanent AF with a rapid ventricular response.2
Standard beta-blockers (such as atenolol or bisoprolol)
or rate-controlling calcium channel blockers (such as
verapamil or diltiazem) are the agents of choice for
controlling heart rate.1,2
Digoxin is only recommended for patients who are
mainly sedentary since it does not offer adequate rate
control during exercise.2
Furthermore, medicine choice for rate control will be
influenced by any comorbidities (see Box 1, p360).

Paroxysmal AF
In paroxysmal AF the episodes of arrhythmia, known as
paroxysms, are self-limiting. The objective of therapy is to
reduce the frequency, or to prevent the occurrence, of
paroxysms and to control the ventricular rate during
episodes to minimise the likelihood of haemodynamic
compromise.
Some patients have infrequent paroxysms that are
associated with minimal symptoms and resolve
spontaneously; these patients may not require drug
treatment for their arrhythmia (although they might need
antithrombotic therapy for stroke prevention).

Figure 1: European Society of Cardiology guidance for the acute management of AF1
Recent-onset atrial fibrillation (<48 hours)

Haemodynamic instability

Yes

Electrical cardioversion

Patients starting amiodarone therapy (in particular)

should receive thorough advice on side effects
information in the British National Formulary can be used
to guide counselling.

Rate control Generally, a patients heart rate is

considered controlled when the ventricular response to AF

Clinical Pharmacist

* Ibutilide is not available in the UK

No

Structural heart disease

Yes

No

Amiodarone IV

Flecainide IV
Propafenone IV
Ibutilide IV*

359

CLINICAL FOCUS

atrial thrombus before cardioversion by confirming that

the AF started within the past 48 hours.

November 2010

CP, Nov, CF2, p358-62_Layout 1 27/10/2010 15:17 Page 360

CLINICAL FOCUS

360

Clinical Pharmacist

November 2010

Vol 2

A pill-in-the-pocket strategy can be appropriate for

certain patients with infrequent but symptomatic
paroxysms.2 This approach involves the patient using
medicines such as flecainide or propafenone on an as
required basis to restore SR rapidly when a paroxysm
occurs. These patients should be assessed fully to exclude
left-ventricular dysfunction or valve disease before
implementing such a strategy.
For patients with more frequent episodes, or more
severe symptoms, ongoing drug treatment to suppress AF
episodes should be started. First-line treatment for all
patients is a standard beta-blocker. Flecainide,
propafenone or sotalol should be considered second line in
the absence of structural heart disease. Sotalol, in
particular, should be used as second-line therapy for
patients with coronary artery disease. For patients with
structural heart disease, amiodarone is recommended for
second-line treatment of paroxysmal AF.1,2
Patients with paroxysmal AF should be advised to avoid
any known precipitants such as alcohol, caffeine or stress.

A PILL-IN-THEPOCKET STRATEGY
CAN BE
APPROPRIATE FOR
CERTAIN PATIENTS
WITH INFREQUENT
BUT SYMPTOMATIC
PAROXYSMS

Vernakalant Vernakalant is a sodium and potassium

channel blocker with atrial-selective, anti-arrhythmic
effects. Placebo-controlled studies have demonstrated that
vernakalant can chemically cardiovert patients.5,6
The AVRO study demonstrated that vernakalant could
cardiovert patients to SR significantly faster than
intravenous amiodarone 51% of patients reverted to SR
at 90 minutes with vernakalant compared with 5.2% with
amiodarone (P=0.0001).7
In September 2010, vernakalant was granted marketing
approval in the EU for the rapid conversion of recentonset AF to SR in adults. Vernakalant is likely to be
launched in the UK in the coming months.
The exact place of vernakalant in therapy has not been
determined, but it is possible that it could rival first-line
therapies in the management of recent-onset AF. However,
cost may limit its use in clinical practice. At the time of
writing, vernakalant was not scheduled for review by NICE.

Specialist, non-pharmacological strategies are available to

manage AF for patients who have failed pharmacological
treatment strategies, or those who are suspected to have
underlying electrophysiological disorders. Examples of
such specialist interventions are:
Implantable atrial defibrillators or atrioverters:
these are devices that function like pacemakers,
delivering electrical impulses with the aim of
maintaining SR. Because the shock they deliver can
be strong and somewhat painful, they are best suited
to those with recurrent rather than a permanent AF
Pulmonary vein isolation: this is the ablation of
cardiac tissue around the pulmonary veins to treat
patients with paroxysmal AF. These areas are often
the origin of ectopic beats that precipitate some
attacks of paroxysmal AF
Atrioventricular (AV) nodal ablation: this involves
the destruction of AV nodal tissue to prevent the
conduction of AF waves to the ventricles and is a
highly effective method of controlling ventricular
rate. Following the procedure, patients require
implantation of a permanent pacemaker to maintain
ventricular rate thereafter
The maze procedure: a surgical procedure whereby
a number of small cuts are made in the atrial wall.
These prevent the rapid and unco-ordinated

Box 1: Choice of medicine for rate control

CLASS OF DRUG

ISCHAEMIC HEART
DISEASE

HYPERTENSION

HEART FAILURE

Beta-blockers

++

+/

++

Calcium channel
+
blockers

++

Digoxin

+/

Key: ++ Strongly indicated; + May be of benefit; +/ Equivocal benefit; Avoid

depolarisation of atrial cells and therefore interrupt

the signals responsible for initiating and
perpetuating episodes of AF

New medicines

Non-pharmacological strategies

+/

Electrocardiogram showing AF, characterised by a lack of P waves

Dronedarone Dronedarone, a new oral antiarrhythmic,

was launched in the UK in 2010. It has a similar
mechanism of action to amiodarone but, in line with other
antiarrhythmics, is less effective at attaining and
maintaining SR.
Despite this, dronedarone has some substantial
advantages over amiodarone including a simple dosing
regimen, shorter half-life, far less onerous monitoring
requirements and fewer toxic adverse effects.
Placebo-controlled studies have demonstrated that
dronedarone can maintain SR better than placebo, but not
better than amiodarone. Relapse rates with dronedarone
remain high (around 60%).810
NICE guidance recommends dronedarone be used for
patients who have failed to respond to first-line therapy and:11
Have hypertension requiring at least two
different classes of medicine
Have diabetes mellitus
Have a history of transient ischaemic attack, stroke
or systemic embolism
Have a left-atrial diameter of 50mm or greater or
left-ventricular ejection fraction less than 40%
Are 70 years of age or older
Do not have unstable New York Heart Association
class III or IV heart failure

Vol 2

Risk assessment People with AF are five times more

warfarin is the standard of care, with the aim of

maintaining the international normalised ratio between 2
and 3. However, the duration of anticoagulant therapy in
patients converted to SR remains a subject of much
debate.1,3
Emerging data suggest that newer agents may challenge
the central role of warfarin in AF stroke prevention.
The RE-LY study compared the direct thrombin
inhibitor dabigatran with open-label warfarin for stroke
prevention in patients with AF. The results indicate that
dabigatran is at least as good as warfarin in preventing AF-

Box 2: Risk of stroke in AF using CHADS213

The CHADS2 score is a tool used to calculate the risk of a patient with
atrial fibrillation having a stroke, based on their medical history and
comorbidities.
A patients CHADS2 score is calculated by assigning points as described
below:
RISK FACTOR

POINTS

Chronic heart failure (current or history of)

Hypertension (current or history of)

Age greater than 75 years

Diabetes mellitus

Stroke or transient ischaemic attack (current or history of)

A patients resulting CHADS2 score corresponds to the stroke risk for that
patient (see below):
CHADS2
SCORE

STROKE RISK PER 100

PATIENT YEARS

CHADS2 RISK LEVEL

ANTITHROMBOTIC
RECOMMENDED

1.9

Low

Aspirin or no
treatment

2.8

Low

Aspirin or warfarin

4.0

Moderate

Warfarin

5.9

Moderate

Warfarin

8.5

High

Warfarin

12.5

High

Warfarin

18.2

High

Warfarin

361

CLINICAL FOCUS

Stroke prevention

Anticoagulation For patients in AF, anticoagulation with

Clinical Pharmacist

related stroke.16 Low-dose dabigatran (110mg twice daily)

was as effective as warfarin with a lower risk of bleeding,
while higher-dose dabigatran (150mg twice daily) offered
greater protection against stroke with equivalent bleeding
risk. Despite this, the number needed to treat (NNT) to
accrue the benefit is large: the NNT to prevent one
haemorrhagic stroke with dabigatran 150mg twice daily
compared with warfarin is 357.
The ROCKET AF trial a randomised, double-blind
study comparing the direct factor Xa inhibitor rivaroxaban
with warfarin for stroke prevention in AF is expected to
be reported at the American Heart Association conference
this year.
The advantages of these newer medicines are simpler
dosing regimens and fewer ongoing monitoring
requirements. Nonetheless, there are concerns about
compliance with medicines that do not require the
intensive monitoring of warfarin, something that cannot be
tested in clinical trials.
In addition, the costs of the newer medicines are likely
to be substantially higher than the current costs associated
with warfarin, even taking into account the costs of INR
monitoring.
It is expected that dabigatran and rivaroxaban will gain
licences for the prevention of stroke in patients with AF

This position allows amiodarone to be reserved for

patients who fail dronedarone therapy while minimising
exposure of certain patients to the toxic side effects of
amiodarone. It is expected that dronedarone use will be
limited to secondary care specialists while clinical
experience is gained. Shared care arrangements may be
required to ensure adequate monitoring, particularly of
renal function, following initiation. [EDITOR for more
information on dronedarone see Clinical Pharmacist
2010;2:334.]

likely to have a stroke than people without AF. In addition,

AF-related strokes are more severe and associated with
more disability than non-AF strokes. Adequately
controlled anticoagulation with warfarin reduces the risk
of stroke for patients with AF by 68% and can prevent
three out of four AF-related strokes.12
Risk-scoring systems are needed to balance the benefits
of preventing stroke against the risk of bleeding with oral
anticoagulants. Numerous systems to assess stroke risk
have been developed, but the most commonly used in
clinical practice is the CHADS2 score (see Box 2).
According to CHADS2, the bleeding risk outweighs the
benefit of anticoagulation for patients with fewer risk
factors, but for patients with multiple risk factors, or with
prior stroke or transient ischaemic attack, the benefits of
oral anticoagulation outweigh the bleeding risk. Data from
clinical trials suggest an annual risk of bleeding of
approximately 2% with warfarin.12,14 Accordingly, warfarin
is recommended for all patients with a stroke risk greater
than the bleeding risk, that is a CHADS2 score 2.
This year has seen the introduction of an extended risk
factor scoring system to replace CHADS2, known as
CHA2DS2 VASc, although this has yet to be incorporated
into UK clinical practice.15

November 2010

CLINICAL FOCUS

362

Clinical Pharmacist

November 2010

Vol 2

within the next 12 months, and NICE health technology

appraisals are expected shortly after licensing.
Many more oral anticoagulants are in development and
are expected to be licensed in the coming years.

Now put your learning into practice by joining

colleagues at a CPPE learning@lunch flex
session in your hospital. During the session you
will test your knowledge with five reflective
questions and three true-to-life case studies.
You will discuss the most
appropriate treatment
strategy for James, a 63year-old man admitted to
your A&E department with
suspected paroxysmal atrial
fibrillation. The questions
will invite you to consider
the side effects associated
with antiarrhythmic drugs
and explore the challenges of initiating
and monitoring patients on amiodarone.
For more information about taking part in a
learning@lunch flex session or setting up your
own learning community, turn to the contact
details on p358.

Try our Lifelong Learning modules

at www.clinicalpharmacist.com

2
3

6
7

10

11

12

13
14

15
16

European Society of Cardiology. Guidelines for the management of atrial

fibrillation. European Heart Journal 2010. www.escardio.org (accessed 10
September 2010).
National Institute for Health and Clinical Excellence. Atrial fibrillation.
June 2006. www.nice.org.uk/cg36 (accessed 10 September 2010).
Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and
rhythm control in patients with atrial fibrillation. New England Journal of
Medicine 2002;347:182533.
Camm AJ, Kirchhof P, Lip GYH, et al. Atrial fibrillation. In: Camm AJ,
Luscher TF, Serruys PW, eds. The ESC textbook of cardiovascular
medicines, 2nd Edition. London: Oxford University Press; 2009.
www.esctextbook.oxfordonline.com (accessed 10 September 2010).
Kowey PR, Dorian P, Mitchell LB, et al. Vernakalant hydrochloride for the
rapid conversion of atrial fibrillation after cardiac surgery. Circulation:
arrhythmia and electrophysiology 2009;2:6529.
Roy D, Pratt CM, Torp-Pedersen C, et al. Vernakalant hydrochloride for
rapid conversion of atrial fibrillation. Circulation 2008;117:151825.
Camm AJ, Capucci A, Hohnloser S, et al. A randomized active-controlled
study comparing the efficacy and safety of vernakalant to amiodarone in
recent onset atrial fibrillation. Journal of the American College of
Cardiology 2010; in press.
Singh BN, Connolly SJ, Crijns HJGM, et al. Dronedarone for maintenance
of sinus rhythm in atrial fibrillation or flutter. New England Journal of
Medicine 2007;357:98799.
Hohnloser SH, Crijns HJGM, van Eickels M, et al. Effect of dronedarone
on cardiovascular events in atrial fibrillation. New England Journal of
Medicine 2009;360:66878.
Le Heuzey J, De Ferrari GM, Radzik D, et al. A short-term, randomized,
double-blind, parallel-group study to evaluate the efficacy and safety of
dronedarone versus amiodarone in patients with persistent atrial fibrillation.
Journal of Cardiovascular Electrophysiology 2010;21:597605.
National Institute for Health and Clinical Excellence. Dronedarone for the
treatment of non-permanent atrial fibrillation. August 2010.
www.nice.org.uk/ta197 (accessed 10 September 2010).
Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus
aspirin for prevention of thromboembolism in atrial fibrillation: Stroke
prevention in atrial fibrillation II study. Lancet 1994;343:68791.
Gage BF, Waterman AD, Shannon W, et al. Validation of clinical
classification schemes for predicting stroke. JAMA 2001;285:286470.
Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of
antithrombotic therapy in atrial fibrillation. Archives of Internal Medicine
1994;154:144957.
Lip GY, Frison L, Halperin J, et al. Identifying patients at risk of stroke
despite anticoagulation. Stroke 2010; in press.
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in
patients with atrial fibrillation. New England Journal of Medicine
2009;361:113951.

clinical
pharmacist

Act

Plan

Atrial fibrillation

ifelong Learning questions are available to complete in an

online module on the Clinical Pharmacist section of PJ Online
accessible via www.clinicalpharmacist.com.
To complete the module, you will need to log in to the site. If
you are a new visitor, it is simple to register as a user (registration is
free to all Royal Pharmaceutical Society members).

Questions
This months Lifelong Learning questions are based on the CLINICAL
FOCUS articles on atrial fibrillation, commissioned from independent
authors. The information in the Box (below) is there to help you
identify knowledge gaps and undertake continuing professional
development. This online module will close on 1 February 2011.

Answers
When you have completed the online module, your answers will be
submitted for marking and Clinical Pharmacist will send you a
certificate and your results by email within two weeks of the module
closing. Please do not hesitate to contact us if you have technical
problems with the module. E: clinicalpharmacist@pharmj.org.uk

How to undertake CPD

References
1

Reflect

Evaluate

Our CLINICAL FOCUS articles and the

online Lifelong Learning modules
can help you plan your CPD
and record the benefits of the
activity at www.uptodate.org.uk.

Reflect on your gaps in

knowledge
Why does atrial fibrillation
(AF) occur and how are the
various types of AF
classified?
What are the different
treatment strategies for AF
and which medicines are
used?
How can strokes be prevented
in patients with AF?

Act to enhance your practice

Read the CL NICAL FOCUS articles
in this issue (pp35562)

Test your knowledge by

completing the questions at
www.clinicalpharmacist.com

Evaluate the activity

What have you learnt?
How has it added value to
your practice?

What will you do now and

how will this be achieved?
The questions in this
Lifelong Learning module have
been approved by the Royal
Pharmaceutical Society using
an independent reviewer as a
resource to support your
professional development.

Consider making this activity

one of your nine CPD entries
this year

Answers from Septembers module

Atopic eczema
1

(a) T, (b) T, (c) T, (d) F, (e) F

(a) T, (b) F, (c) F, (d) T, (e) T

(a) F, (b) T, (c) T, (d) T, (e) F

(a) F, (b) F, (c) T, (d) F, (e) T

(a) T, (b) T, (c) F, (d) F, (e) F

(a) T, (b) F, (c) F, (d) T, (e) F

(a) F, (b) F, (c) T, (d) T, (e) T

(a) T, (b) F, (c) T, (d) F, (e) T

(a) T, (b) F, (c) F, (d) T, (e) F

10

(a) F, (b) F, (c) T, (d) F, (e) T