ANTICOAGULATE CAMPAIGN CLINICIANS TOOLKIT - BOOKLET SINGLE PAGE

www.weahsn.net
Declaration; The Programme is funded through a joint
working project between Bayer Healthcare and West
of England AHSN
This document was funded with an unrestricted educational
grant from Boehringer-Ingelheim
V2.0: (06/02/15)
Clinical guidance
Preventing
AF related stroke

What is this toolkit for?
It is intended to support clinicians in making decisions
about AF-related stroke prevention and anticoagulation
for people with AF. It has been produced as part of the
‘Don’t Wait to Anticoagulate’ project.
Declaration; The Programme is funded through a joint working project between Bayer Healthcare
and West of England AHSN

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withatrialfibrillation(AF)
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35
PrevalenceofAF
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inUKpopulation
1.6%
0.5%
9%
aged50-59
aged80-90
800,000
250,000
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peoplearecurrently
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Fromtheageof55
thelikelyhoodof
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Anticoagulation
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7,000strokes
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Everyyear
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arecausedbyAF
Mortalityratefromstroke
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thatofpeoplewith
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peoplewithAFwillhave
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arenotanticoagulated
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2
£12,000inthefirstyearalone
peoplewithAFstill
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becausetreated
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ofanticoagulants
230,000
...areonaspirinorarenoton
anticoagulationatall.
...theydonothaveanAFdiagnosis.
Nearly50%ofpeoplewithAF
arenoteffectivelyprotected
againststrokebecause
...labileINR.
...don’t wait to
anticoagulate

Contents
Section One
Clinical Overview: The Case for Change 1
Section Two
AF-related Stroke Prevention: Guides to Clinical Practice 9
1. West of England AF–related stroke prevention guidance
2. Key factors influencing anticoagulant choice in Non-Valvular AF
3. Oral anticoagulants: Frequently Asked Questions
4. Identifying stroke bleed risk
5. Managing predicting bleeding switching between anticoagulants
6. Anticoagulating the frail and elderly
7. Managing patients with a labile INR
8. Shared decision making with patients
9. Local formulary guidance
References38

Section One:
Clinical Overview: The Case for Change
Foreword
Dr Jim Moore, Stoke Road Surgery, Gloucestershire, Cardiology
GPwSI and Clinical Lead for AF Stroke Prevention
Atrial fibrillation (AF) is a major cause of stroke. The 2014 National
Institute for Health and Clinical Excellence (NICE) publication, Atrial
Fibrillation: The Management of Atrial Fibrillation, resulted in a welcome
focus on the risks of stroke associated with AF. Thousands of strokes
in the UK are avoidable with both the timely identification of patients
with AF and the appropriate management of their thromboembolic
risk with anticoagulation. The risk of stroke is five times greater in a
patient with AF and the associated disability and mortality are also
significantly increased when compared to strokes in patients with a
normal cardiac rhythm.
It is no coincidence that the guidelines published both nationally
and internationally in the last few years emphasise the importance
of addressing stroke risk early in the assessment and management
of patients with newly diagnosed AF. Those same guidelines have
additionally stressed that Aspirin should no longer be seen as a
safe and effective drug for stroke prevention in AF patients, and
most importantly should not be considered as an alternative
to anticoagulation.
In recent years we have seen the introduction of several new oral
anticoagulants (NOACs) available with NICE approval for use in AF
patients. NOACs have been shown in clinical trials to be “non inferior”
to warfarin in their ability to reduce stroke, and in addition to warfarin,
they provide increased anticoagulant choice and flexibility in the
management of stroke risk.
Lastly and most importantly, progress in this area will best be
achieved through a balanced and honest dialogue with patients about
the risks of stroke and the potential benefits of treatment. The recent
NICE guidance supports this, highlighting “the need for a personalised
package of care and information” as a key recommendation.
1

Foreword
Jo Jerrome
Deputy CEO AF Association
Atrial fibrillation (AF) is a common heart arrhythmia. The number of
patients with AF is rising and we expect this to continue, with GRASP-
AF data for England showing a prevalence rate of 1.8%. Symptoms
of AF can include breathlessness, palpitations, dizziness and chest
discomfort. However, the condition can also remain silent and
asymptomatic.
Either way, AF is the single most powerful independent risk factor
for stroke.
As well as being more deadly and disabling, AF-related strokes are
also more expensive. Every AF-related stroke costs the NHS almost
£12,000 pounds in the first year - putting a disproportionately high
burden both on healthcare budgets and on those providing care,
either formally or informally.
Early diagnosis and appropriate management with an anticoagulant
can prevent at least two thirds of AF-related strokes suffered annually.
Consequently there is urgent need for the improved diagnosis and
management of AF to prevent thousands suffering avoidable strokes,
disability and premature death.
In order to improve health outcomes for people with AF and to achieve
significant financial savings in the NHS, it is imperative that more AF
patients in need of anticoagulation are identified. The tools included
within this package provide extensive and significant support to
facilitate accurate assessment and appropriate management of AF
for patients and clinicians. The Don’t Wait to Anticoagulate resources
reflect national guideline recommendations in practical, manageable
and supportive tools.
Life with AF can be long and healthy when patients are able to
appropriately manage and control this potentially devastating and
debilitating condition. The power to do so is in a well-informed
partnership between patient and clinician. This toolkit provides the
inspiration and know-how to initiate and make a real difference to
the lives of AF patients and those close to them.
2

Introduction
Dr Matthew Fay, GPwSI in Cardiology, Westcliffe Medical Practice,
Bradford, and member of the NICE Guideline Development Group
We often hear that there is an epidemic of AF coming with the ageing
population. The truth is that it is already upon us. In the UK there are
a million or more patients suffering from the dysrhythmia, and as a
result, shouldering the risk of stroke. With the development of better
risk assessment tools and alternative anticoagulants emerging since
the 2006 NICE Clinical Guideline, it has become clear that further
guidance is needed to ensure that patients receive the best and most
appropriate treatment.
The CG180 shows a simplified assessment of stroke, working from
the view that all patients require intervention to minimise their risk of
AF-related stroke apart from the small minority without risk features;
that the risk factors for bleeding complications should be identified
and where possible minimised and that the patient should choose the
intervention best suited to their personal situation.
With only 1 in 2 of those at risk protected against stroke, the guideline
is a ‘call to arms’ for every clinician to support our patients with AF to
prevent at least 7,000 strokes per year which are devastating the lives
of patients and their carers.
The assessment of stroke risk should be undertaken using the
CHA2DS2-VASc risk score. Calculations using this assessment tool use
a greater number of risk factors than the more commonly used CHADS
tool, giving additional emphasis to the importance of older age, female
gender and pre-existing vascular disease as risk factors for stroke.
CHA2DS2-VASc identifies those at truly low risk who do not require
treatment for their stroke risk. Changing the paradigm for seeking
those at risk of AF related stroke to an attitude of wishing to treat all
but those at very low risk of AF stroke
In those at high risk of stroke and eligible for anticoagulation we
should routinely assess their bleeding risk using the HAS-BLED risk
calculator identifying those risk factors which we can address and
modify thereby reducing the risks of anticoagulation. Rarely will the
bleeding risk be such that anticoagulation is not offered to a patient at
high risk of stroke.
3

A stroke physician’s perspective
Dr Louise Shaw, Consultant Physician MB, ChB, FRCP, Royal
United Hospital, Bath
I have seen a dramatic increase in the prevalence of AF and its
consequences on the Acute Stroke Unit at the RUH in the past
five years. Firstly, the incidence of AF rises rapidly with age and
our population is living longer than ever before. Secondly, a person
is 5 times more likely to have a stroke if they are in AF than if they are
in sinus rhythm. It is predicted that the prevalence of AF will double
over the next 30 years, although already in 2014 I find that almost half
of the patients on my stroke unit have AF as a cause of their stroke.
Having a stroke in itself is devastating; however strokes caused by
AF tend to be more severe than strokes from other causes. AF stroke
patients are:
• Twice as likely to die as a patient in sinus rhythm.
• More likely to become seriously disabled.
• More likely to end up bedridden and in a nursing home.
It is important to be aware that the risk posed by AF is the same
whether the AF is asymptomatic, paroxysmal or persistent. Patients
with CHA2DS2-VASc 1 or higher should be anticoagulated. The default
position should be ‘Opt Out, not Opt In’. Aspirin is ineffective at
preventing AF strokes and is not an acceptable substitute.
A lot of stroke deaths and disability can be prevented by simple stroke
prevention at all opportunities in all health settings. The most important
aspect is a manual pulse check. If there is an irregular pulse, an ECG
is needed. If AF is confirmed, always consider anticoagulation. This
simple check can have a profound impact.
Key messages for GPs
The case for change needs to be actioned by us all.
Everyone who is involved in the AF pathway needs to “think
anticoagulation” and ask “Why should we not anticoagulate
this patient?” We therefore need to embed a culture in our
practice where:
• We use every opportunity to look for AF.
• CHA2DS2-VASc 1 or more means that anticoagulation is
necessary.
• Antiplatelets are no longer an acceptable or appropriate
treatment for AF.
4

Summary of NICE Clinical Guideline 180 on the
management of AF
Dr Matthew Fay
CG180 Background
Atrial fibrillation (AF) is the most common
sustained arrhythmia, with a prevalence of 1.7%
in the general practice population and over 10%
in the practice population 65 years of age.
It is associated with significant morbidity and
mortality both as a result of symptoms caused
by rhythm disturbance, and from increased
stroke risk. Although some patients present
with cardiovascular symptoms of palpitations,
and breathlessness/dyspnoea, AF may often
be asymptomatic. It is commonly associated
with other cardiovascular risk factors such as
hypertension, diabetes, structural heart issues,
occlusive vascular disease, and advancing
age (≥75 years).
CG180 Patient-centred care summary
Support for people with AF should be centred
on their needs and personal choices. With
rhythm management in AF failing to reduce
mortality or stroke risk, the need to intervene
is based purely on the patient’s dysrhythmia
symptoms, which can vary greatly between
individuals. The benefits and risks of
anticoagulants should be outlined to the patient.
Clinician concerns regarding haemorrhagic
risk are misaligned with patient concerns as
to the risk of stroke, often making it difficult
to support clinical decision making. For this
reason, an updated Patient Decision Aid
was produced by NICE at the same time
as Clinical Guideline (CG) 180.4 After initial
management, on-going review of the patient is
needed to: assess symptoms associated with
AF progression, the risk/benefit of intervention
with anticoagulants, and the quality of
anticoagulation if a vitamin K antagonist (VKA)
is used to ensure time in therapeutic range.
CG 180 Stroke risk reduction summary
Stroke related to AF is largely avoidable with
appropriate assessment and intervention. There
has been a paradigm shift in the attitude to
stroke risk assessment meaning that all but
those with no risk factors should be considered
for intervention. The CHA2DS2-VASc is
recommended for assessment of risk in AF.
Anticoagulation should be offered to those
with a score of 2 or above, taking bleeding
risk into account, and should be considered
for those with a score of 1 (except if they are
aged 65 years and the point is due to gender
alone). The HAS-BLED tool should be used
to assess bleeding risk in patients starting
anticoagulation, to demonstrate how bleeding
risk can be reduced by risk factor modification.
The type of anticoagulant, VKA or non-VKA
oral anticoagulant, should be agreed with
the patient, taking into account their clinical
circumstances and personal preferences.
Individuals with no risk factors (or only gender
as a risk factor) do not require anti-thrombotic
intervention. Antiplatelet monotherapy with
aspirin should not be offered to patients
with AF solely for stroke prevention. If an
anticoagulant is contraindicated or not
tolerated should a left atrial appendage
occlusion be considered.
The risks and benefits should be discussed
with the patient.
The first consideration for symptom
management should be rate control except
in situations where:
• AF has a reversible cause.
• AF is thought to have caused heart failure.
• The patient has new onset AF.
5

3
www.eGuidelines.co.uk
Stroke prevention of people with non-valvular AF
Assess stroke risk stratification
using CHA2
DS2
-VASc
Discuss risks and benefits of anticoagulation
Identify low risk patients i.e. CHA2
DS2
-VASc = 0 (men) or 1 (women)
Left atrial appendage occlusion
Annual review for all patients
Assess bleeding risk stratification
using HAS-BLED
No antithrombotic therapy
CHA2
DS2
-VASc ≥2
Offer oral anticoagulant
CHA2
DS2
-VASc = 1 (in men)
Consider oral anticoagulant
Discuss the options for anticoagulation with the person and
base the choice on their clinical features and preferences
Non-VKA oral anticoagulant
Vitamin K antagonists (VKA)
Assess anticoagulation control
Non-VKA oral anticoagulant
[See TA numbers 249, 256, 275]
People who choose not to have treatment
Low risk
Anticoagulation
contraindicatedPoor control
Non-VKA contraindicated or not tolerated
References
1. NICE. Atrial fibrillation: the management of
atrial fibrillation. Clinical Guideline 180. NICE,
2014. Available at: www.nice.org.uk/guidance/
CG180
2. Cowan C, Healicon R, Robson I et al. Heart
2013; 99 (16): 1166–1172.
3. National Clinical Guideline Centre. Atrial
fibrillation: the management of atrial
fibrillation. Clinical Guideline. 2014, NICE.
4. NICE. Atrial fibrillation: medicines to help
reduce your risk of a stroke—what are the
options? Patient decision aid. NICE, 2014.
Available at: guidance.nice.org.uk/CG180/
PatientDecisionAid/pdf/English
Algorithm reproduced with permission from: National Clinical Guideline Centre. Atrial Fibrillation.
Clinical Guideline 180, Methods, evidence and recommendations. National Clinical Guideline Centre, 2014.
Available at: www.nice.org.uk/guidance/cg180/resources/cg180-atrial-fibrillation-update-full-guideline3
Non-VKA oral anticoagulants are rivaroxaban, dabigatran, and apixaban
• Atrial flutter is diagnosed and the patient’s
condition is suitable for ablation therapy.
• Clinical judgement suggests a rhythm
control strategy could be more suitable.
If rate control with beta-blockers, diltiazem,
or digoxin, individually or any two in
combination, is unsuccessful in symptom
management then a rhythm control strategy
should be considered.
The guideline recommends that patients
should be referred promptly (within 4 weeks)
for specialised management if symptoms
remain uncontrolled, despite treatment.
In patients with symptomatic paroxysms of AF
we should initially consider pharmacological
interventions; however, if this strategy fails to
control the AF then ablation therapy should
be considered.
6

Antiplatelet therapy – Does it still have a place in AF
Stroke prevention?
Dr Jim Moore
For too long the use of aspirin has been
considered as a reasonable alternative to
anticoagulation in protecting AF patients.
The evidence supporting the use of aspirin is
unconvincing. A meta-analysis comparing the
use of aspirin with placebo or no treatment
in patients with AF showed a non-significant
19% reduction in the incidence of stroke in
the aspirin treated group. This compares
unfavourably with similar studies looking at
dose adjusted warfarin that showed a highly
significant 64% reduction in stroke incidence.
The risk reduction achieved by aspirin is
very similar to that achieved when it is used
as prophylaxis in patients with established
vascular disease. Vascular disease is
a common finding in patients with atrial
fibrillation and the limited benefit of aspirin in
this group of patients is likely to be due to its
effect on vascular disease.
Guidelines for using aspirin
Recommendations in recent guidelines written
both in the UK and abroad1
clearly state that
aspirin monotherapy should not be used as
thromboprophylaxis for patients with AF as
the modest benefit derived from taking aspirin
is offset by the risk of major bleeding or
intracranial haemorrhage.
Dual antiplatelet therapy in the form of
aspirin combined with clopidogrel may
provide better protection against stroke but
at the expense of increased bleeding. As a
consequence some guidelines recommend
that dual therapy should not be offered as
thromboprophylaxis. Recent NICE guidance
does suggest that this combination may be
considered in exceptional circumstances
for patients who are intolerant of all forms of
anticoagulant therapy or where anticoagulants
are contraindicated.
It is worth noting that the majority of patients
unsuitable for anticoagulant therapy are so
because they are at increased risk of major
bleeding and, as dual antiplatelet therapy
increases the risk of serious bleeding, it
should not be considered in this group.
The use of aspirin with warfarin therapy in
patients who have either chronic AF alone
7
1. NICE CG 180, Royal College of Physicians of Edinburgh UK Consensus Conference 2012;
European Society of Cardiology Focussed update on management of AF 2012

or the combination of chronic AF and stable
vascular disease does not further reduce
the risk of arterial thromboembolism when
compared to those on oral anticoagulant
therapy alone. Antiplatelet drugs (aspirin or
clopidogrel) may be used in the short term
with anticoagulant therapy for AF patients with
concomitant coronary artery disease (CAD)
following ACS or PCI. Such combination
therapy is associated with an increased risk of
bleeding and it is therefore recommended that
warfarin should be used alone in patients with
AF and stable vascular disease.
Aspirin for elderly patients
Elderly patients are commonly denied
anticoagulation and prescribed aspirin in
preference to warfarin because of concerns
over their risk of haemorrhage associated
with falling. Research suggests that an
anticoagulated patient would have to fall 295
times for the risks associated with falling to
outweigh the benefits in stroke reduction.
Reassuringly, the Birmingham Atrial Fibrillation
Treatment of the Aged study (BAFTA) also
showed that AF patients aged ≥75 years had
no significant difference in the risk of major
bleeding (or intracranial bleeding) when those
taking warfarin were compared to patients
given aspirin.
In summary, NICE guidance recommends
oral anticoagulants as first-line therapy
for AF patients at increased stroke risk.
Anticoagulation should be offered to people
with a CHA2DS2VASc score of 2 or more, and
considered for men with a CHA2DS2VASc
score of 1, taking bleeding risk into account.
Aspirin monotherapy should not be offered
solely for protection against stroke and should
be used in combination with clopidogrel only
in exceptional circumstances.
8

Overview of AF-related stroke prevention guides
The following guides are intended to assist
clinicians in managing the anticoagulation
of people with AF.
Guidance is designed to support primary
care clinicians in the anticoagulation of
AF patients.
The decision to initiate anticoagulation and
by what therapy remains a clinical decision,
and should be made following discussions
with patients.
Working in tandem with the 2014 update
to the NICE AF (CG180), this toolkit
provides a wealth of resources to aid the
decision making process for GPs and to
promote shared decision making in AF
thromboprophylaxis. It also aims to address
myths surrounding the anticoagulation of
patients through the presentation of the
best available evidence including input from
haematology.
Most importantly, this toolkit includes the
West of England; Optimising Anticoagulation
to Prevent AF-Related Stroke Protocol.
This document should provide a platform
when clinical consideration is being given
to the decision to initiate a patient on
anticoagulation.
In line with NICE updates, the toolkit also
provides information on the use of antiplatelet
monotherapy in AF thromboprophylaxis.
Contents
1. West of England AF–related stroke
prevention guidance
2. Key factors influencing anticoagulant
choice in Non-Valvular AF
3. Oral anticoagulants: Frequently
Asked Questions
4. Identifying stroke bleed risk
5. Managing predicting bleeding
switching between anticoagulants
6. Anticoagulating the frail and elderly
7. Managing patients with a labile INR
8. Shared decision making with patients
9. Local formulary guidance
Section Two:
Af–Related Stroke Prevention:
Guides to Clinical Practice
9

AF-related stroke prevention guide 1:
West of England AF-related stroke
prevention guidance
West of England Anticoagulation for
AF Related Stroke Prevention Guidance
All AF Patients with non-valvular (paroxysmal, persistent or permanent)
Assess stroke risk stratification using CHA2DS2-VASc
Increased risk: CHA2DS2-
VASc score
= ≥2 (consider men ≥1)
Assess bleeding risk stratification using HAS-BLED
NOTE: BENEFITS OF STROKE PREVENTION OUTWEIGH
RISK OF BLEED AT ALMOST ANY HAS-BLED LEVEL
(for guidance)
Discuss risks and benefits of anticoagulation
No anticoagulation at
current point
Low risk or patient declines
treatment (review as per
review criteria)
No anticoagulation at
current point
Unmodifiably high bleed risk
or patient declines treatment
(review as per review criteria)
Discuss options for anticoagulation with patient and base choice on clinical features and preferences
Review criteria for anticoagulation for AF stroke prevention
a) All patients with a new
diagnosis of AF
b) Patients with existing
diagnosis of AF e.g
identified through audit
c) All AF patients when
turning 65 and over
d) Patients with labile
INRs (discount initial
6 weeks):
• 2 INR values 5 or
1 INR value 8 within
past 6 months
• 2 INR values 1.5
within less than
6 months
• TTR less than 65%.
e) Annually from decision
to not anticoagulate
f) For all AF patients on
development of:
• Diabetes
• Heart failure
• Peripheral arterial
disease
• Coronary heart disease
• Stroke, transient
ischaemic attack
• Systemic
thromboembolism.
• Hypertension
ANTICOAGULATE
DABIGATRAN, RIVAROXABAN, APIXABAN
Consider for patients who:
• are not taking warfarin because of allergy or
intolerance or where INR monitoring is impractical
(access to Renal LFTs monitoring necessary)
• have labile INR despite evidence of adherence or
practical difficulties with treatment
• have drug interactions with warfarin
• ask to start a NOAC
ASPIRIN IS NOT EFFECTIVE IN PREVENTING AF RELATED STROKE AND SHOULD NOT BE
INITIATED IN AF PATIENTS IN PLACE OF ANTICOAGULATION
WARFARIN
Consider for patients who:
• when reviewed are currently well controlled on warfarin
• are at risk of drug interactions with a NOAC
• have CrCL (eGFR) 30 ml/min
Note:
• consider bridging with heparin or LWMH for acute
onset AF or for patients at a high risk of stroke
• consider self-monitoring where appropriate
• calculate TTR at each patient contact
• review warfarin use if Iabile INR
...don’t wait to
anticoagulate
Low risk:
CHA2DS2-VASc score
= 0 (men) or 1 (women)

V1: Draft Jan 2015
Declaration; The Programme is funded through a joint working
project between Bayer Healthcare and West of England AHSN
10

Key factors influencing anticoagulant choice in
Non-Valvular AF
Licensing
All novel OACS (NOACs) are licensed for
prevention of stroke in non valvular AF plus
at least one additional risk factor. Warfarin is
licensed for use without additional risk factors
present. http://www.medicines.org.uk/emc/
NICE Guidance and patient choice
The decision about whether to start treatment
with any anticoagulant in AF should be made
after an informed discussion between the
clinician and the patient about the risks and
benefits of individual agents.
Compliance
NOACs are not a safe option in patients
who are not suitable for warfarin for reasons
of poor compliance or in those deemed to
have too high a risk of bleeding for warfarin.
Patients prescribed NOACs should have an
on-going review of treatment, preferably after
one month and then on a 3-monthly basis1
.
Risk of haemorrhage
NOACs have been demonstrated to have
a lower risk of catastrophic intracerebral
haemorrhage but some (Rivaroxaban and
Dabigatran 150mg) have a slightly higher
risk of gastrointestinal haemorrhage.
Reversal
The major concern with the new
anticoagulants is the lack of an effective
antidote. This is counterbalanced to
some degree by the lower risk of severe
haemorrhage reported within clinical trials
when compared to warfarin. NOACs however
have a relatively short half-life compared to
warfarin and protocols for managing
bleeding events in NOAC treated patients
are available.
Acute bleeding
In the event of acute bleeding patients
receiving a NOAC may require surgical
haemostasis, fluid replacement or blood
products. These may also be appropriate
for those receiving warfarin in addition to
vitamin K. Suggested approaches to the
management of bleeding complications are
outlined in the EHRA practical guide on the
use of NOACs1
Renal function
Dose reduction (or cessation) of the newer
drugs is required with reduced renal function
Frequency of dosing
Dabigatran and Apixaban require twice
daily dosing, compared to once daily for
Rivaroxaban and warfarin.
Extremes of BMI
The relative dose of NOACs may vary by
20-30% at extremes of bodyweight (50 kg
or 100-120 kg). This may be problematic
given the difficulties in monitoring the
therapeutic effects.
Specific indications
E.g. need for elective cardioversion, plans
for ablation etc. Where continuation of
anticoagulation therapy, up to and during
the procedure, would be considered
advantageous, the use of a NOAC could be
appropriate where patient compliance can be
11

reliably confirmed. Warfarin may however be
preferred given the possibility of reversal in
the case of major bleeding.
Monitored Dosage Systems
Neither warfarin nor Dabigatran is suitable for
use in a compliance aid.
Comparative costs
Each of the newer drugs has a considerably
higher acquisition cost than warfarin. When
the cost of INR monitoring is taken into
account, warfarin is likely to remain the least
expensive option up-front. Comparative
cost-effectiveness is not clear. If a NOAC
is preferred and where all other factors are
equal the NOAC with the lowest acquisition
cost should be chosen
Time in therapeutic range
The newer drugs are likely to be more
beneficial in patients whose INR is regularly
outside the therapeutic range despite good
medication adherence.
INR testing
INR testing with warfarin is time consuming,
but provides an opportunity to monitor
adherence and effectiveness.
Experience
Compared to warfarin, there is less clinician
experience of long term use of the NOACs.
Identifying patients taking anticoagulants
Patients anticoagulated with either warfarin or
newer agents should carry a card identifying
their medication and who to contact in case
of emergency related to their anticoagulation.
When might warfarin be the
preferred option?
In patients with a history of GI problems
warfarin may be the preferred option as it
has a more favourable GI side effect profile,
and was associated with a lower rate of GI
haemorrhage compared with Rivaroxaban
and Dabigatran (at the 150 mg twice daily
dose). Compared with warfarin, Apixaban
does not significantly alter the risk of major
GI bleeding. Warfarin has the additional
advantage of being reversible.
Patients on co-administered medication
Some co-administered medications may
inhibit metabolism and potentiate bleeding
risk with novel agents (e.g. azole anti
fungals, ritonavir) are probably safer
managed on warfarin as the INR may
be adjusted accordingly. Patients will
still need appropriate dose adjustment
of warfarin on commencement or
withdrawal of such therapy.
Active swapping from warfarin to
novel agents
Where patients are established on warfarin
with a stable INR there is little or no reason
to actively swap over to novel agents.
Inadequate control of INR may be a reason
to consider a NOAC as are warfarin-specific
side effects e.g. alopecia. There is a potential
for inadequate anticoagulation during the
transition between OACs.
12

Frequently Asked Questions
1. How do oral anticoagulants work?
Warfarin2
Dabigatran3
Rivaroxaban4
Apixaban5
Inhibits the
production
of vitamin K
dependent clotting
factors II, VII, IX
and X
Acts as a direct
thrombin (factor
IIa) inhibitor. It
is formulated
as Dabigatran
etexilate; a pro-
drug converted to
Dabigatran after
administration.
Acts as a selective
direct factor Xa
inhibitor. Inhibition
of Factor Xa
interrupts the
intrinsic and
extrinsic pathway
of the blood
coagulation
cascade, inhibiting
both thrombin
formation and
development of
thrombi.
Inhibits free
and clot-bound
factor Xa, and
prothrombinase
activity. Apixaban
prevents thrombin
generation
and thrombus
development.
No direct effects
on platelet
aggregation, but
indirectly inhibits
aggregation
induced by
thrombin.
13

2. What are their main contraindications?
Warfarin Dabigatran Rivaroxaban Apixaban
Known
hypersensitivity
to warfarin or any
excipients
Haemorrhagic
stroke
Clinically significant
bleeding
Within 72 hours
of major surgery
with risk of severe
bleeding
Within 48 hours
postpartum
Pregnancy (first and
third trimesters)
Drugs where
interactions
may lead to
a significantly
increased risk of
bleeding
Hypersensitivity
to the active
substance or any
excipients.
Severe renal
impairment (CrCL
30 mL/min)
Active clinically
significant bleeding.
Any lesion
or condition
considered a
significant risk
factor for bleeding.
Concomitant
treatment with any
other anticoagulant
Hepatic impairment
or liver disease
expected to have
any impact on
survival.
Concomitant
treatment
with systemic
ketoconazole,
cyclosporine,
itraconazole,
tacrolimus,
dronedarone.
Prosthetic heart
valves requiring
anticoagulant
treatment.
Hypersensitivity
to the active
substance or any
excipients.
Active clinically
Concomitant
treatment with any
other anticoagulant
Hepatic disease
associated with
coagulopathy and
clinically relevant
bleeding risk
including cirrhotic
patients with Child
Pugh B and C
Pregnancy and
breast feeding.
Prosthetic heart
valves requiring
anticoagulation
treatment
Severe renal
impairment (CrCL
15ml/min)
Dronaderone
and other drug
interactions
Hypersensitivity
to the active
substance or any
excipients.
Active clinically
Hepatic disease
associated with
coagulopathy and
clinically relevant
bleeding risk.
Any lesion
or condition
considered a
significant risk
factor for bleeding.
Concomitant
treatment with any
other anticoagulant
Prosthetic heart
valves requiring
anticoagulation
treatment
Severe renal
impairment (CrCL
15ml/min)
Dronaderone
and other drug
interactions
14

3. Do the preparations contain wheat and lactose?
4. When should specific OACs be avoided?
Yes - Lactose
Yes - Maize starch
(Marevan)
No - lactose
No - wheat
Yes- Lactose
No - wheat
Yes -Lactose
No - wheat
Warfarin Dabigatran, Rivaroxaban, Apixaban
Intolerance to
warfarin including
allergy and rash.
Demonstrated
impossibility
of monitoring
arrangements
Warfarin is
teratogenic and
should not be given
in the first trimester
of pregnancy
AVOID in patients with a history of poor medication adherence
(unless poor adherence relates to e.g. difficulty managing flexible
warfarin dosage that may be addressed through a fixed dose
regime)
The NOACs are not a suitable alternative to warfarin in patients
with bleeding complications associated with warfarin treatment,
contraindications to warfarin therapy due to a high bleeding risk,
alcohol abuse, drug overdose or trivial side effects related to
warfarin.
Dabigatran is not stable in compliance aids such as dosette boxes.
Manufacturers advise to avoid use in pregnancy.
15

Tests prior
to starting
treatment
Clotting screen,
U E’s, LFTs,
FBC, BP, CrCl,
Thyroid status
Ongoing
monitoring
requires
adjustment to
the individual
needs of the
patient and
therefore
requires regular
monitoring using
blood tests.
Tests prior to starting
treatment
Clotting screen, U E’s,
LFTs, FBC, BP, CrCl
Monitoring until
patient is stabilised
Ideally assess every
3 months to:
• Assess compliance
and reinforce
advice regarding
regular dosing
schedule.
• Enquire about
adverse effects
such as bleeding.
• Assess for the
presence of
thromboembolic
events
• Enquire about
other medicines,
including OTC
medicines.
Ongoing monitoring
U E’s, LFTs, FBC
at least once a year
especially in elderly
and patients with
renal impairment.
treatment
Clotting screen, U E’s,
LFTs, FBC, BP, CrCl
Monitoring until
Ideally assess every
3 months to:
and reinforce
advice regarding
regular dosing
schedule.
• Enquire about
adverse effects
such as bleeding.
• Assess for the
presence of
thromboembolic
events
• Enquire about
other medicines,
including OTC
medicines.
Ongoing Monitoring
U E’s, LFTs, FBC at
least once a year.
Repeat UE’s every
treatment
Clotting screen, U
E’s, LFTs, FBC, BP,
CrCl, body weight
Monitoring until
Ideally assess patient
every 3 months to:
and reinforce advice
regarding regular
dosing schedule.
• Enquire about
adverse effects
such as bleeding.
• Assess for the
presence of
thromboembolic
events
• Enquire about other
medicines, including
OTC medicines
Ongoing monitoring
U E’s, LFTs, FBC at
least once a year.
Repeat UE’s every 6
months if CrCl 30–60
Repeat UE’s every
6 months if CrCl
30–60 mL/min, patient
75 years or fragile.
Repeat UE’s every
3 months if CrCl
15–30 mL/min.
More frequent UE’s/
LFTs advised where
intercurrent illness
may impact on renal
or hepatic function.
6 months if CrCl 30–
60 mL/min or every 3
months if CrCl 15– 30
mL/min.
LFTs advised where
may impact on renal
mL/min or every 3
months if CrCl 15–30
mL/min.
LFTs advised where
may impact on renal
5. What pre-testing and monitoring are necessary?
16

6. What doses should be given and what adjustments as necessary
for renal impairment?
Dabigatran Rivaroxaban Apixaban
(CrCl above
50ml/min)
Patients under 80 years:
150 mg twice daily
Patients 80 years:
110 mg twice daily
(due to the increased
risk of bleeding in this
population)
Reduce to 110 mg
twice daily in patients
who are taking
verapamil
Consider 110 mg
twice daily when the
thromboembolic risk is
low and the bleeding
risk is high (e.g. CrCL
30-50 mL/min) or
patients weigh 50kg.
20 mg once daily with
food
5 mg twice daily
Reduce to 2.5 mg
twice daily in patients
with two or more
of the following
characteristics:
Age ≥80 years
Body weight ≤60kg
Serum creatinine
≥1.5mg/dL (133
micromoles/L)
CrCl
30-49ml/min
110-150mg twice daily Reduce dose to 15mg
daily
Use normal dose
CrCl
15-29ml/min
Do not use Reduce dose to 15mg
daily
Reduce dose to 2.5mg
twice daily
CrCl
15ml/min
Do not use Do not use Do not use
Warfarin
For patients who require rapid anticoagulation the usual adult induction dose of warfarin is
5–10 mg on the first day (elderly patients should receive a lower induction dose).
For patients who do not require rapid anticoagulation, a lower loading dose can be used
over 3–4 weeks.
In both cases subsequent doses depend upon the prothrombin time, reported as INR
(international normalised ratio).
Consider Apixaban in preference to warfarin with eGFR of 30–50 ml/min/1.73 m2.
17

7. How safe are oral anticoagulants?
Warfarin Dabigatran, Rivaroxaban, Apixaban
Long-term safety
based on 50 years
use in clinical
practice
No information available on long-term safety.
Reduce dose in renal impairment (based on Cockcroft Gault
calculation of CrCl)
8. What are the main drug interactions?
Warfarin Dabigatran Rivaroxaban, Apixaban
Drug-food
interactions
Cranberry juice
and alcohol
interact with
warfarin. Some
foods interact with
warfarin (e.g. foods
containing high
amounts of
Vitamin K).
Drug-drug
interactions
Many interactions
requiring additional
INR monitoring.
Drug-food interactions
There are no known food
interactions.
Drug-drug interactions
Contraindicated with the strong
P-gp inhibitors ketoconazole,
cyclosporine, itraconazole,
tacrolimus and dronedarone.
Use with caution if co-administered
with mild to moderate P-gp
inhibitors such as amiodarone,
quinidine, verapamil, ticagrelor.
Co-administration with P-gp
inducers such as rifampicin, St
John’s Wort, carbamazepine or
phenytoin) should be avoided.
SSRIs and SNRIs increased the
risk of bleeding in RE-LY in all
treatment groups.
Drug-food interactions
There are no known food
interactions.
Drug-drug interactions
Not recommended with
concomitant systemic
administration of strong
inhibitors of both CYP3A4
and P-gp, such as
ketoconazole, itraconazole,
voriconazole, posaconazole
or HIV protease inhibitors.
Strong inducers of
both CYP3A4 and P-gp
(such as rifampicin,
phenytoin, carbamazepine,
phenobarbital or St John’s
Wort) should be co-
administered with caution
because of the risk of a loss
of effectiveness.
Concomitant administration with any other anticoagulants is contraindicated (some overlap
may be necessary whilst transferring between anticoagulants).
Consult the SPC for full details of interactions.
18

9. What are the common side effects?
Nausea, vomiting,
diarrhoea, jaundice,
alopecia, rash,
hepatic dysfunction,
pyrexia
Dyspepsia more
frequent with both
doses of Dabigatran
than warfarin. GI
adverse events
frequently led to
drug discontinuation
(7%, 6.5% and
3.9% in the
Dabigatran 150
mg, 110 mg and
warfarin groups
respectively)4
.
The rate of
myocardial
infarction (MI) was
numerically, but
not statistically
significantly, higher
with Dabigatran
in the pivotal trial
(0.82% for 110
mg and 0.81% for
150 mg vs. 0.64%
p=0.12).7-9
A meta-analysis
combining 7
studies showed
Dabigatran was
associated with a
significantly higher
risk of MI or ACS.
The control group
varied and included
enoxaparin, warfarin
and placebo.10
There were
no significant
differences in the
incidence of any
adverse event other
than bleeding in the
pivotal Rivaroxaban
trial.11
The rate of MI was
numerically, but
not statistically
significantly lower,
in the Rivaroxaban
arm compared with
warfarin.
There were
no significant
differences between
warfarin and
Apixaban in the
incidence of any
adverse events
in the pivotal
Apixaban trial.12
19

Identifying stroke bleed risk
CHA2DS2-VASc and HASBLED
Dr Dipankar Dutta, Consultant Physician, Gloucestershire Royal Hospital
Using CHA2DS2-VASc to assess stroke risk
The CHA2DS2-VASc stroke risk score should
be used in people with paroxysmal, persistent,
or permanent AF (regardless of symptoms),
atrial flutter, and people with continuing risk of
AF recurrence after cardioversion.
The GRASP-AF toolkit includes options to
risk stratifies patients using CHA2DS2-VASc
scores. The tool also highlights those who
would benefit from review to assess their
appropriateness for anticoagulation.
CHA2DS2-VASc HAS-BLED
Item Score Item Score
C Congestive heart failure 1 H Hypertension (uncontrolled BP) 1
H Hypertension 1 A Abnormal renal/ liver function 1 or 2
A2 Age≥ 75 years 2 S Stroke history 1
D Diabetes mellitus 1 B
Bleeding tendency or
predisposition
1
S2
Previous stroke, TIA or
thromboembolism
2 L Labile INR 1
V
Vascular disease (MI, PVD, aortic
plaque)
1 E Elderly (Age ≥ 65 years) 1
A Age 65 -75 years 1 D
Drugs (concurrent aspirin or
NSAIDs ) or alcohol
1 or 2
Sc Sex category (female gender) 1
Maximum total 9 Maximum total 9
Anticoagulation with warfarin or NOACs should be considered in men with a CHA2DS2-VASc
score of 1. Men or women with a CHA2DS2-VASc score of 2 or above should definitely be
offered anticoagulants.
Assessment of bleeding risk using HAS-BLED
Use of the score prompts users to identify bleeding risk factors which, in some instances, may be
modifiable. It must be emphasised it is not primarily intended to deny people anticoagulants but to
identify modifiable risk factors, such as hypertension, high alcohol intake, and the use of concurrent
aspirin and NSAIDs, that could be addressed. In most instances, preventing strokes will take
priority over avoidance of a bleed.
20

Managing predicting bleeding
switching between anticoagulants
When a patient is anticoagulated they can encounter bleeding either
spontaneously or as a result of trauma. In primary care, your role is
to reassure patients that regardless of the anticoagulant agent used;
there are procedures to deal with bleeding effectively. Practices
should consider the key actions to be taken for the management of
anticoagulation associated bleeding in primary care, including the
development of an emergency policy. The management of patients
post-bleed should also be considered in planning the practice stroke
prevention action plan.
For anticoagulated patients in primary care, the key to good management
is to ensure that they are sent to an accident and emergency department
immediately if they are actively bleeding or bleeding from a significant site
e.g. the eye. This is a situation where calling an ambulance for the patient
should be employed.
Once the patient is in hospital the level of bleeding will be assessed.
This assessment will direct care for bleeding associated with both
warfarin and novel oral anticoagulants (NOACs), as seen in table 1.
If a patient has a major bleed, they will be kept in hospital where their
anticoagulation and drug therapies will be reviewed. All changes
should be recorded in the discharge letter to the GP surgery.
It is important that as the practice nurse managing a patient’s
anticoagulation, you are aware of these events and changes, and
arrange to review their care.
Management of bleeding associated with anticoagulation
The approach taken to the management of bleeding will depend on
the type of anticoagulant used. It is therefore important to ensure that
staff managing the bleeding are aware of the anticoagulant that has
been prescribed.
Warfarin
Over anticoagulation and bleeding can occur as a result of non-
compliance, drug interactions, liver failure, variations in diet, misuse
of alcohol and underlying conditions e.g. gastric ulcer. Management
is dependent on the international normalised ratio (INR) and the
presence of active bleeding. Treatments include stopping warfarin
for a short time, the use of the antidote Vitamin K and in more severe
bleeding, the Prothrombin Complex Compound (PCC).
21

3
primary care your role is to ensure that the patient is referred to secondary care in a timely
manner, which we will be discussing further during this webinar.
Table 1: Management of warfarin associated bleeding (adapted from BCSH 2011)
Identify warfarin indication and therapeutic INR range, as well as the patient’s weight
Urgent blood tests to be taken: full blood count, clotting screen, INR, urea and
electrolytes, liver function test
** Hemoglobin drop 2.0g/l and/or bleeding in a critical site
o Administer PCC as soon as available from laboratory
o Re-check INR within 30-60 min after administration
o Contact Haematologist if INR not reversed or ongoing bleeding is taking place
INR 5.0
No evidence of bleeding
Reduce warfarin dose
INR 5.0 plus bleeding
Start resuscitation measures
Monitor blood pressure and urine output
Life threatening
bleeding **
And/or emergency surgery
As for moderate
bleeding plus give
Vitamin K 10mg IV
Contact Haematologist
for PCC
Moderate bleeding **
Local first aid measures
including surgery
Give Vitamin K 5-10mg IV
Contact Haematologist
Consider PCC
Mild or no bleeding
If other risk factors
for bleeding reversal is
required in 48 hours
Give Vitamin K orally
1-2mg
Restart warfarin when
INR 5.0 at reduced
dose
NOACs
Studies have shown that the bleeding profile of NOACs especially with
regard to life-threatening bleeding, is more favourable than warfarin.
However, as more people start taking NOACs the number of bleeds is
expected to rise.
22

1. Does the risk of a bleed vary between OACs?
See respective
agent for
comparison
Major bleeding:
No difference
between Dabigatran
150 mg BD and
warfarin. Less
common with
Dabigatran 110 mg
BD than warfarin
GI bleeding:
More common with
Dabigatran 150 mg
BD than warfarin
(p=0.0008). No
difference between
Dabigatran 110 mg
BD and warfarin.
Intracranial
bleeding:
Less common
with both doses
of Dabigatran
than with warfarin
(p0.001).
Bleeding risk high
in the frail and
elderly, particularly
with renal
impairment and low
body weight.
Major bleeding:
No difference
between
Rivaroxaban and
warfarin.
GI bleeding:
More common with
Rivaroxaban than
warfarin (p0.001)
Intracranial
bleeding:
less common with
Rivaroxaban than
warfarin (p=0.02)
Major bleeding:
Less common with
Apixaban than
warfarin (p0.001)
GI bleeding:
No difference
between Apixaban
and warfarin
Intracranial
bleeding:
Less common with
Apixaban than
warfarin (p0.001)
23

2. Can bleeding be reversed?
3. What are the half-lives of the OACs?
Effective and well
known antidote,
should a severe
bleed occur whilst
being treated
No antidote
currently known.
Patients with
bleeding risk factors
excluded from
pivotal trial.
Clearance can
be increased with
haemodialysis.
Prolonged bleeding
has increased
morbidity and
possibly contributed
to deaths13
.
No antidote
currently known
although
prothrombin
complex
concentrate has
been successful
in showing
normalisation of
laboratory clotting
parameters
(prothrombin time
and endogenous
thrombin potential)
in a small
preliminary trial.14
No antidote
currently known
About
40 hours
GFR [mL/min] half-life (range)
hours]
5 to 9 hours
in young
individuals,
11 to 13 hours
in the elderly.
12 hours
≥ 80 13.4 (11.0-21.6)
≥ 50- 80 15.3 (11.7-34.1)
≥ 30- 50 18.4 (13.3-23.0)
30 27.2 (21.6-35.0)
24

4. How should the dose of OACs be adjusted when patients are having dental
treatment or surgery?
Warfarin
OAC use with no
clinically important
bleeding risk
Dental procedures — outpatient dental surgery (including
extractions) can usually be undertaken without temporarily stopping
or reducing the dose of warfarin. It is recommended that the INR
is checked 72 hours before dental surgery. The risk of significant
bleeding in people with a stable INR within the range of 2 to 4
is very small, but the risk of thrombosis may be increased if oral
anticoagulants are temporarily discontinued
Surgery — in general, warfarin is usually stopped 5 days before
planned surgery, and once the person’s international normalised
ratio (INR) is less than 1.5 surgery can go ahead. warfarin is usually
resumed at the normal dose on the evening of surgery or the next
day if haemostasis is adequate.
OAC use and
undergoing surgery
with a low bleeding
risk
OAC use and
undergoing surgery
with a high bleeding
risk
Restarting OACs
after surgery
See local guidelines. Treatment should be restarted after the
invasive procedure or surgical intervention as soon as possible
provided the clinical situation allows and adequate haemostasis
has been established as determined by the treating physician.
Onset of action of NOACs is much faster than that of warfarin.
25

Dabigatran Rivaroxaban Apixaban
OAC use
with no
clinically
important
bleeding
risk
The procedure can be performed just before the next dose of Dabigatran,
Rivaroxaban or Apixaban is due, or approximately 18–24 hours after the
last dose was taken (treatment should be restarted 6 hours later).
For dental procedures, consider prescribing tranexamic acid 5% mouth
wash; instruct the person to use 10 mL as a mouth wash four times a day
for 5 days.
OAC
use and
undergoing
surgery
with a low
bleeding
risk
Dabigatran should be
stopped 24 hours before
the procedure.
If the person has creatinine
clearance 50–80 mL/min
the intervention.
the intervention.
Rivaroxaban should
be stopped 24
hours before the
procedure.
If the person has a
creatinine clearance
between 15–30 mL/
min Rivaroxaban
should be stopped
36 hours before the
procedure.
Apixaban should
be stopped 24
hours before the
procedure.
If the person has a
between 15–30
mL/min, Apixaban
should be stopped
36 hours before the
procedure.
OAC
use and
undergoing
surgery
with a high
bleeding
risk
the procedure.
the intervention.
the intervention.
Rivaroxaban should
be stopped 48
hours before the
procedure.
If the person has a
between 15–30 mL/
min Rivaroxaban
should be stopped
96 hours before the
procedure.
Apixaban should
be stopped 48
hours before the
procedure.
If the person has a
between 15–30
mL/min Apixaban
should be stopped
96 hours before the
procedure.
Restarting
OACs after
surgery
See local guidelines. Treatment should be restarted after the invasive
procedure or surgical intervention as soon as possible provided
the clinical situation allows and adequate haemostasis has been
established as determined by the treating physician. Onset of action of
NOACs is much faster than that of warfarin.
26

Predicting Bleed Risk when managing anticoagulation for surgical procedures
No clinically important
bleeding risk
• dental interventions such
as; extraction of 1 to 3
teeth, periodontal surgery,
incision of abscess and
implant positioning,
cataract or glaucoma
interventions.
• endoscopy without
surgery.
• minor surgery (e.g.
abscess incision and
small dermatologic
excisions).
Examples of low bleeding
risk (not exhaustive)
• endoscopy with biopsy.
• prostate or bladder
biopsy.
• electrophysiological
study or radiofrequency
catheter ablation
for supraventricular
tachycardia (including
left-sided ablation via
single trans-septal
puncture).
• angiography.
• pacemaker or implantable
cardioverter defibrillator
(icd) implantation (unless
complex anatomical
setting, e.g. congenital
heart disease).
Examples of high bleeding
risk (not exhaustive)
• complex left-sided
ablation (pulmonary vein
isolation; vt ablation).
• spinal or epidural
anaesthesia.
• lumbar diagnostic
puncture.
• thoracic surgery.
• abdominal surgery.
• major orthopaedic
surgery.
• liver biopsy.
• transurethral prostate
resection.
• kidney biopsy.
27

4
bleeding, is more favourable than warfarin. However, as more people start taking NOACs the
number of bleeds is expected to rise.4
Bleeding Direct thrombin
(dabigatran)
Factor Xa inhibitors
(rivaroxaban /apixaban )
Possible measures
*
*
Table 2: Possible measures to take in case of NOAC associated bleeding4
linical
• Establish last dose and dosing
regime
• Estimate normalisation of
haemostasis, depending on renal
function
o Normal renal function 12-24 hours
o CrCl 50-80 mL/min 24-36 hours
o CrCl 30- 50 mL/min 36-48 hours
o CrCl 30mL/min ≥ 48 hours
• Maintain diuresis
• Local haemostasis measures
• Fluid replacement
• Red blood cell (RBC) substitution
if necessary
• Plasma substitution if necessary
• Fresh frozen plasma as plasma
expander (not reversal agent)
• Tranexamic acid can be considered
as adjuvans
• Desmopressin can be considered in
special cases
• Consider dialysis
• All of the above
• PCC 25U/kg
• Activated PCC – if PCC not
available
• Activated Factor VII (rFVIIa 90
µg/kg)
o no data about additional
benefit and it is expensive
Non life-
threatening
bleeding
Life-
threatening
bleeding
• Establish last dose and dosing
regime
• Normalisation of haemostasis
12-24 hours
• Maintain diuresis
• Local haemostasis measures
• Fluid replacement
• Red blood cell (RBC) substitution
if necessary
• Plasma substitution if necessary
• Fresh frozen plasma as plasma
expander (not reversal agent)
• Tranexamic acid can be considered
as adjuvans
• Desmopressin can be considered in
special cases
• All of the above
• PCC 25U/kg
• Activated PCC – if PCC not
available
• Activated Factor VII (rFVIIa 90
µg/kg)
o no data about additional
benefit and it is expensive
28

Table 2 shows that there are slightly different measures to administer
depending on which NOAC has been taken. In addition, as NOACs
have a relatively short elimination half life, it is important to note that
time is an important antidote. This means that it is very important that
you discover when a patient took their last anticoagulation dose and
send this information to the hospital as soon as possible.
The hospital will also need details of which drug they are using, their
medical history, specifically history of liver or kidney disease and any
other factors that influence haemostasis, such as antiplatelet therapy.
As with warfarin, appropriate transfer to AE is extremely important.
5. Switching between anticoagulants
It is important to safeguard the continuation of anticoagulant therapy
whilst minimising the risk of bleeding when switching between different
anticoagulant therapies.
29

How do you
switch between
anticoagulants?
There is a
potential for
inadequate
anticoagulation
during the
transition
between NOACs
and Warfarin.
Continuous
adequate
anticoagulation
should be
ensured during
any transition to
an alternative
anticoagulants
When
converting
patients from
warfarin therapy
to a NOAC,
discontinue
warfarin and
start:
• Dabigatran
when the INR
is below 2.0
• Rivaroxaban
when INR is
below 3.0
• Apixaban
when INR is
below 2.0
INR values
will be falsely
elevated after
the intake of
Rivaroxaban.
When converting
from Dabigatran
to warfarin, adjust
the starting time
of warfarin based
on creatinine
clearance as
follows:
For CrCl50mL/
min, start
warfarin 3
days before
discontinuing
Dabigatran.
For CrCl 31-
50mL/min,
start warfarin
2 days before
discontinuing
Dabigatran.
For CrCl 15-
30mL/min,
start warfarin
1 day before
discontinuing
Dabigatran
When
converting from
Rivaroxaban
to warfarin,
Rivaroxaban
should be
continued until
the INR is
≥ 2.0.
For the first
two days of
the conversion
period, standard
initial dosing
of warfarin
should be used
followed by
warfarin dosing
guided by INR
testing.
While patients
are on both
Rivaroxaban
and warfarin,
the INR should
When
converting
from Apixaban
to warfarin,
continue
Apixaban
for at least
2 days after
starting warfarin
therapy.
After 2
days of co-
administration
of Apixaban
and warfarin,
obtain an INR
prior to the next
scheduled dose
of Apixaban.
Continue co-
administration
of Apixaban
and warfarin
until the INR is
2 or more
For CrCl15mL/
min, no
recommendations
can be made
– consult with
haematologist.
Because
Dabigatran can
contribute to an
elevated INR,
the INR will
better reflect
warfarin’s effect
after Dabigatran
has been
stopped for at
least 2 days.
not be tested
earlier than 24
hours after the
previous dose
but prior to the
next dose of
Rivaroxaban.
Once
Rivaroxaban is
discontinued
INR testing
may be done
reliably at least
24 hours after
the last dose
30

Converting
from parenteral
anticoagulants
The exact
regimen
depends on
individual
circumstances.
Parenteral
anticoagulants
are generally
continued until
the INR is in the
desired range.
Discontinue
the parenteral
anticoagulant
and start
Dabigatran 0-2
hours prior to
the time that the
next dose of the
alternate therapy
would be due,
or at the time of
discontinuation
in case of
continuous
treatment.
For patients
currently
receiving a
parenteral
anticoagulant,
Rivaroxaban
should be
started 0 to 2
hours before
the time of the
next scheduled
administration of
the parenteral
medicinal
product (e.g.
low molecular
weight
heparins) or
at the time of
discontinuation
of a
continuously
administered
parenteral
medicinal
product (e.g.
intravenous
unfractionated
heparin).
Switching
treatment from
parenteral
anticoagulants
Apixaban (and
vice versa) can
be done at the
next scheduled
dose. These
agents
should not be
administered
simultaneously.
31

AF-related stroke prevention guide 6: Anticoagulating
Anticoagulating the frail and elderly
Dr Gopinath Ramadurai, Stroke Physician, Dr Sameer Maini, Consultant Physician and
Geriatrician, Great Western Hospital, Swindon
Atrial fibrillation (AF) is the most common
sustained arrhythmia which tends to increase
in incidence with age. AF has a prevalence of
around 7% in persons aged 65 or over and
increases to over 12% in those aged 75 or
over. AF is an independent risk factor for stroke,
causes more severe strokes, and can account
for up to 25% of strokes in patients aged 80-89.
Anti-coagulation with warfarin or one of the
novel anti-coagulant agents (NOACs) is now
the mainstay in prevention of stroke in the
population with AF especially the frail elderly
(NICE guidelines, CG180, June 2014). But
the fear of increased risk of bleeding added
to the risk of falls has led physicians to be
cautious in using anti-coagulants in this group
of patients. Widespread poly-pharmacy and
non-compliance with monitoring has also added
to the underuse of anti-coagulation in this
population with the highest stroke risk.
Anti-coagulation and falls risk –
Addressing the myths
Elderly patients are at increased risk of falls.
Studies point out that approximately one-third
of patients over the age of 65 years fall every
year. Many physician surveys have pointed
out falls as the main deterrent to the use of
warfarin. A meta-analysis which studied the risk
of anti-thrombotic use in elderly at high falls
risk concluded that the propensity for falling
alone should not be used as an important factor
when deciding whether the patient should be
a candidate for anti-coagulation. Studies have
also shown that an elderly patient on warfarin
should have approximately 300 falls per year
or at least one fall per day for the risks of
warfarin to outweigh its benefits. The most
common bleeding risk score (HAS-BLED) does
not include falls when calculating the bleeding
risk. If a falls risk is identified, then the priority
should be to take measures that minimise this
risk, which include environmental modification,
medication review and treating the underlying
medical cause of falls instead of withholding
anticoagulation.
Novel anti-coagulants in anti-
coagulating the elderly
Novel anticoagulants (Dabigatran, Rivaroxaban,
Apixaban) provide a very good alternative to
warfarin especially in patients where a tight
control is difficult and medicine compliance
is difficult. Also the newer agents have shown
good ischemic stroke reduction that is non-
inferior to warfarin without an increase in
hemorrhagic strokes. The novel agents also
come with the convenience of fixed daily
dosing without the need for monitoring and less
susceptibility to drug or food interactions.
Anti-coagulation in the frail elderly can provide
a considerable challenge as this is the
population at the highest risk of stroke but also
perceived to be at high risk of complications
due to anti-coagulation.
Available evidence suggests that these risks
are overemphasized, especially falls and
the risk of falling alone should not be used
as a reason to withhold anti-coagulation.
Recognising patients at risk of falling should
be used as a trigger to identify risk factors
for falls and subsequently managing them to
minimise this risk. The use of NOACs could
reduce complications in carefully selected
patients. Finally, involving the patient in this
decision making process about the risks and
benefits of anti-coagulation could minimise the
complication rates and improve compliance.
32

Managing patients with a labile INR
Sue Rhodes, VTE Specialist Nurse and Joint Anti-Coagulant Lead, Great Western Hospital
The time in therapeutic range (TTR) is one
indicator of poor compliance. However,
when making a decision as to whether this
can be used to assess for suitability for a
NOAC other factors need to be taken into
consideration.
Measuring INR
To measure the effectiveness of warfarin
patients need to have regular INR blood tests.
The INR is a standardised test to measure
the clotting ability of the blood. People not
taking warfarin will have a normal INR of
approximately 1.0. Once a patient is given
warfarin the INR will be raised. The level that
it should be raised to will depend on the
condition being treated. In AF the target INR
should be 2.5. However it is acceptable for
the INR to be within the range of 2.0 and 3.0.
Blood needs to be taken to get the INR result,
either using a citrated tube or a finger prick
test - the venous citrated tube sample is the
most accurate test. A full tube is required and
it needs to be analysed in a laboratory.
Near patient testing with a finger prick test
is potentially more convenient for the patient
however the same rigorous standards
as for venous samples must be applied.
All equipment must be regularly quality
controlled and meet stringent NEQAS
(National External Quality Assessment
Service) standards. Further information about
NEQAS services can be obtained
www.ukneqasbc.org
Poor control
A patient’s most appropriate range will be
decided by their clinician and on-going
monitoring will ensure they are effectively
anticoagulated. Poor control, as defined by
the NICE 2014 AF Guideline, is any of
the following:
• Two INR values higher than 5 or one
INR value higher than 8 within the past
six months
• Two INR values less than 1.5 within the
past six months
• TTR less than 65%
If control cannot be improved a patient’s
stroke prevention strategy will need to be
re-evaluated, and other treatment options
considered.
Initiating warfarin
There are several initiation protocols that are
used to commence warfarin. A baseline INR
should be performed, as well as renal and
liver function tests if applicable.
It is important that whilst a patient is
being ‘loaded’ onto warfarin their INR is
regularly checked. AF patients can be frail
so commencing warfarin should be done
carefully. It is clear that whilst the patient is
insufficiently anticoagulated they are at risk
of clotting and an AF-related stroke. It is not
therefore acceptable for this process to be
extended as necessary. For AF patients with
acute onset AF or at a high risk of stroke
consider bridging with heparin or LWMH.
All patients will need to be counselled about
their condition, the need for anticoagulation
and the safe use of warfarin.
33

In calculating the TTR
• Use a validated method of measurement
such as the Rosendaal method for
computer assisted dosing or proportion of
tests in range for manual dosing
• Exclude measurements taken in the first 6
weeks of treatment
• Calculate TTR over a maintenance period
of at least 6 months
• Exclude any period of deliberately omitted
anticoagulation (e.g. surgical procedure)
• If the TTR is 65% this is an acceptable
level of anticoagulant control
• A TTR of 65% indicates that the patient
requires review of medication and
consideration of additional factors which
may contribute to poor control, such as:
- Cognitive function
- Adherence to prescribed therapy
- Illness
- Interacting drug therapy, including herbal
or over the counter preparations
- Lifestyle factors including diet
and alcohol
If poor anticoagulant control cannot
be improved by adjusting any of these
factors alternative drug therapy with one
of the NOACs needs to be discussed
with the patient.
Patients with diminished
cognitive function
Patients who experience difficulty with taking
variable doses of warfarin and find it difficult
to cope with constantly changing doses
may be suitable for one of the NOACs as
this would give a fixed dose on a once or
twice daily regime giving a constant level of
anticoagulation.
A NOAC may also be more suitable for
patients already utilising a dosette tray for
medicine administration.
Adherence to prescribed therapy
Where patients appear to be genuinely non-
compliant with medicines then a NOAC may
not be more suitable than warfarin due to
their short half-life and therefore increased
risk of stroke if a dose is omitted.
However, if the non-adherence is related to
the difficulty in attending for regular blood
tests then a NOAC may be suitable.
Illness
An illness may have temporarily caused
warfarin therapy to become unstable and in
this case a NOAC may not be more suitable.
Any longer term illness requires options for
anticoagulation therapy to be reviewed and a
NOAC may be more suitable than warfarin. It
would be advisable to seek specialist advice.
34

Interacting drug therapy
Many drugs interact with warfarin. If a known
interacting drug is prescribed resulting in
labile INRs, this may not necessarily be an
indication to prescribe a NOAC.
Ensure adequate INR monitoring is always
actioned whenever an interacting drug is
prescribed concurrently with warfarin as this
will reduce fluctuations in INRs.
If frequent prescriptions of interacting drugs
are necessary such as regular antibiotics
then a NOAC may be more suitable.
Many drugs interact with warfarin. If a known
interacting drug is prescribed resulting in
labile INRs, this may not necessarily be an
indication to prescribe a NOAC.
Ensure adequate INR monitoring is always
actioned whenever an interacting drug is
prescribed concurrently with warfarin as this
will reduce fluctuations in INRs.
If frequent prescriptions of interacting drugs
are necessary such as regular antibiotics
then a NOAC may be more suitable.
Lifestyle factors
Diet and alcohol can have significant
interactions with warfarin therapy resulting
in labile INRs. Patients should be educated
regarding the impact of dietary changes
when taking warfarin and if despite
adhering to recommendations they are still
experiencing labile INRs then a NOAC may
be more suitable.
Excessive, fluctuating alcohol intake will
adversely affect INR stability. For patients
with a low risk of bleeding (utilising the HAS-
BLED scoring system) then a NOAC may be
more suitable.
For patients with a high risk of bleeding
specialist advice should be sought as with a
current lack of a reversal agent a NOAC may
not be suitable.
35

Shared Decision Making with Patients
Shared Decision Making is defined by The
Health Foundation as:
“a collaborative process through which a
health care professional supports a patient
to reach a decision about a specific course
of action, such as deciding on a strategy to
manage pain from knee arthritis.”
The NHS is increasingly focused on
partnership, respect and helping people
take control and responsibility for their own
health. Shared decision making brings
together clinical expertise. In the case of
AF this involves an assessment of risk and
benefit regarding anticoagulation alongside
the patient as an expert in their own lifestyle,
preferences, ideals etc. A shared decision
making approach is particularly useful when
utilized in decisions that carry significant
potential risks and benefits. In the case
of facilitating decision making around
anticoagulation, shared decision making is
essential to promoting good person centred
care as called for by NICE CG180.
Key Guidelines on shared decision
making
1. NICE – CG180 guidance on shared
decision making
(1.2) Personalised package of care and
information
1.2.1 Offer people with AF a personalised
package of care. Ensure that the package
of care is documented and delivered, and
that it covers:
• stroke awareness and measures to
prevent stroke
• rate control
• assessment of symptoms for rhythm control
• who to contact for advice if needed
• psychological support if needed
• up-to-date and comprehensive education
and information on:
• cause, effects and possible complications
of atrial fibrillation
• management of rate and rhythm control
• anticoagulation
• practical advice on anticoagulation in line
with recommendation 1.3.1 in
• ‘Venous thromboembolic diseases’ (NICE
clinical guideline 144)
• support networks (for example,
cardiovascular charities). [new 2014]
2. User guide: Don’t wait to
anticoagulate patient toolkit:
Following extensive patient involvement
and clinical consultation, the Don’t Wait
to Anticoagulate patient toolkit has been
developed based on the NICE patient
decision aid. It is designed to assist
clinicians in explaining and demonstrating
stroke prevention and bleed risk through
personalised risk sheets.
The patient toolkit covers:
• What is AF?
• Update on aspirin
• Risk of major internal bleeding
• Treatment options to reduce risk of stroke
in AF
• Frequently Asked Questions
36

The pack contains a shared decision making
support tool which can be pre populated with
CHADSVASC and HAS-BLED scores as well
as suitable OAC options and can be sent out
with letters calling patients into the practice
for AF review. There is also a shorter guide to
OAC and AF that can accompany the shared
decision making support tool and the risk
and benefit sheets. The tool also includes a
list of questions that patients may wish to ask
clinicians about during the planned review.
The toolkits are also designed to be worked
through in consultation alongside clinicians.
As an innovator practice you can test the
toolkit with patients and make changes to
the process or materials as necessary, but
this should be captured in a PDSA cycle
approach. How the toolkits are used and
shared with patients is a decision to be made
within innovator practices, as the utilisation
of them is a live experiment to find the most
effective way to promote shared decision
making amongst clinicians and patients.
For practices that use System One, it is
possible to download the materials from
within the system. The WEAHSN QIT can
assist with this. Work is currently being
undertaken to trial this within.
3. CARE AF – Supported by Bayer
and in collaboration with AFA
We recommend the CARE AF: Protecting you
from AF-Related Stroke Pack to accompany
the decision aid if required, this was
produced following an update of the NICE
guidelines for AF (June 2014).
The CARE AF pack was produced following
an update of the NICE guidelines for AF
(June 2014) and contains:
1. What is AF, causes and symptoms?
2. How AF is a stroke risk.
3. Practical advice on effective management
and different treatment options.
4. Patient stories and how they live with the
condition.
5. Healthy living – tips for good health
including nutritional advice, exercise tips
and managing stress.
6. Additional information and frequently
asked questions.
Supplies of the CARE AF pack can be
obtained via the WEAHSN QIT.
Resources to support shared decision making:
There are a range of resources designed
to support shared decision making and
patient centred care. The following resources
and links were accurate at the time of print
(November 2011):
• Patient support programme for people with
AF - www.careaf.org
• Further information on Shared Decision
Making: www.personcentredcare.health.org.
uk/person-centred-care/shared-decision-
making/
• Shared Decision Making guide by NHS:
http://sdm.rightcare.nhs.uk/about/shared-
decision-making/
• XIMPACT NURSE: Anticoagulation in Atrial
Fibrillation (AF) webinar series, Bayer
HealthCare, 2014.
• NHS, Shared Decision Making Programme,
Measuring shared decision making: A
review of research evidence, London, 2012.
• Coulter. A, Collins. A, Making Shared
Decision making a reality: No decision
about me, without me, London, The King’s
Fund, 2011.
• Summit report: Leading the way to shared
decision making, The Health Foundation,
2012.
• De Silva.D, Evidence: Helping people share
decision making, The Health Foundation,
2012.
37

Local formulary guidance summaries
Bristol, North Somerset and South
Gloucestershire (BNSSG):
NHS Bristol CCG, NHS North Somerset CCG,
NHS South Gloucestershire CCG, North
Bristol NHS Trust, University Hospitals Bristol
NHS Foundation Trust and Weston Area
Health NHS Trust.
Local Formulary Guidelines:
The Bristol, North Somerset and South
Gloucestershire (BNSSG) Joint Formulary
http://www.bnssgformulary.nhs.uk/28-
Anticoagulants-and-protamine
Decision Aid:
Guidance on the use of Apixaban,
Dabigatran, Rivaroxaban
http://www.bnssgformulary.nhs.uk/includes/
documents/BNSSG%20NOAC%20
Decision%20guideV3%20APRIL%20
13final%20.pdf
Swindon and North Wiltshire:
Great Western Hospitals NHS
Foundation Trust
3T’s Drug Formulary
http://www.gwh.nhs.uk/patients-and-visitors/
pharmacy/3ts-drugs-formulary/guidelines/
AF - Oral Anticoagulant Decision Aid:
http://www.gwh.nhs.uk/media/150917/new_
decision_aid_oct_2013_v5.pdf
Gloucestershire:
Gloucestershire Joint Formulary
Gloucestershire Joint Formulary
http://www.formulary.glos.nhs.uk/en/Content-
Page/Chapter-2---Cardiovascular/#2.8
Prescribing Guideline:
http://www.formulary.glos.nhs.uk/
PageFiles/199/Glos%20NOAC%20for%20
NVAF%20guidance.pdf
Bath and North East Somerset
(BANES):
NHS BANES CCG, NHS Wiltshire CCG, Royal
United Hospital Bath NHS Trust, Avon and
Wiltshire Mental Health Partnership NHS
Trust, Royal National Hospital for Rheumatic
Diseases NHS Foundation Trust
BCAP Formulary
http://www.bcapformulary.nhs.uk/282-oral-
anticoagulants
Decision aid:
Written by Wiltshire CCG
http://www.bcapformulary.nhs.uk/includes/
documents/Updated-decision-aid-for-NOACs-
in-AF-October-2014.pdf
Please note this information was correct at
going to print November 2014. The following
local guidance is relevant only to the CCG
it serves. If your local formulary is not here
please contact local Medicines Management
for further information.
38

References
1. Heidbuchel H et al. EHRA Practical Guide
on the use of new oral anticoagulants in
patients with non-valvular atrial fibrillation:
executive summary. Eur Heart J Apr
2013. www.NOACforAF.eu,
2. Amdipharm Mercury Company Limited.
Summary of Product Characteristics -
Marevan 5 mg tablets. Date of revision of
the text: 18/09/2012.
3. Boehringer Ingelheim. Summary of
Product Characteristics - Pradaxa 150
mg hard capsules. Date of revision of the
text: 07/2013.
4. Bayer plc. Summary of Product
Characteristics - Xarelto 20 mg film-
coated tablets. Date of revision of the
text: June 2013.
5. Bristol-Myers Squibb-Pfizer. Summary of
Product Characteristics - Eliquis 5 mg
film-coated tablets. Date of revision of the
text:12 February 2013.
6. Personal communication, Dr Jane Skinner
Consultant Community Cardiologist,
Newcastle upon Tyne Hospitals.
Sept 2013.
7. Connolly SJ et al. Dabigatran versus
warfarin in Patients with Atrial Fibrillation.
N Engl J Med 2009;361:1139-51.
8. Connolly S et al. Newly identified
events in the RE-LY trial. N Engl J Med
2010;363:1875-6.
9. Hohnloser SH. Myocardial ischaemic
events in patients with atrial fibrillation
treated with Dabigatran or warfarin in
the RE-LY (Randomized Evaluation of
Long-term anticoagulation therapy) Trial.
Circulation 2012;125:669-76.
10. Uchino K et al. Dabigatran Association
With Higher Risk of Acute Coronary
Events: Meta-analysis of Noninferiority
Randomized Controlled Trials. Arch Intern
Med 2012;172:397-402.
11. Patel MR et al. Rivaroxaban versus
warfarin in nonvalvular atrial fibrillation.
N Engl J Med 2010;365:883-91.
12. Granger CB et al. Apixaban versus
warfarin in patients with atrial fibrillation.
N Engl J Med 2011;365:981-92.
13. Harper P. Bleeding risk with Dabigatran
in the frail elderly. N Engl J Med
2012;366:864-6.
14. Eerenberg ES et al. Reversal of
Rivaroxaban and Dabigatran by
prothrombin complex concentrate:
a randomized, placebo-controlled,
crossover study in healthy subjects.
Circulation 2011;124:1573-9.
Additional Key References
A. Suggestions for Drug Monitoring in
Adults in Primary Care 2014 http://www.
medicinesresources.nhs.uk/upload/
documents/Evidence/Drug%20monitoring%20
document%20Feb%202014.pdf
Clinical Knowledge Summaries
http://cks.nice.org.uk/anticoagulation-oral
British National Formulary https://www.
evidence.nhs.uk/formulary/bnf/current
Desai J et al Thromobosis and Haemostasis
2013 https://www5.medicine.wisc.
edu/~williams/NOAC_GI_bleeding_2013.pdf
NICE Guidance CKD 2014. https://www.
nice.org.uk/guidance/cg182/chapter/1-
recommendations
39

West of England Academic Health Science Network
South Plaza
Marlborough Street
Bristol BS1 3NX
T: 0117 900 2604
E: contactus@weahsn.net
National Institute for Health and Care Excellence (2014 Adapted from CG 180 Atrial fibrillation: the management
of atrial fibrillation. Manchester: NICE. Available from www.nice.org.uk/CG180 Reproduced with permission

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