UK/CVS-111026(1) | January 2013 Stroke Prevention in Atrial Fibrillation Treatment guidelines: Developed and funded by UK/CVS-111026(1) | Date of preparation:

UK/CVS-111026(1) | January 2013 UK/CVS-111026(1) | January 2013

Stroke Prevention in Atrial FibrillationTreatment guidelines:

Developed and funded by

UK/CVS-111026(1) | Date of preparation: January 2013

Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at: Xarelto 20 mg: http://www.medicines.org.uk/EMC/medicine/25586/SPCXarelto 15 mg: http://www.medicines.org.uk/EMC/medicine/25592/SPC

Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:Pradaxa 150 mg: http://www.medicines.org.uk/EMC/medicine/24839/SPCPradaxa 110 mg: http://www.medicines.org.uk/EMC/medicine/20760/SPC

Summary of Product Characteristics for apixaban (Eliquis® ) can be found at: Eliquis 5.0 mg: http://www.medicines.org.uk/EMC/medicine/27220/SPCEliquis 2.5 mg: http://www.medicines.org.uk/EMC/medicine/24988/SPC





Stroke Prevention in Atrial FibrillationTreatment guidelines:

UK/CVS-111026(1) | January 2013

Goals of management of AF

Management of AF has two broad objectives:

1. Prevention of complications, including thromboembolism (particularly stroke) and heart failure

2. Relief of symptoms

ESC Guidelines for the management of atrial fibrillation 2010.National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

UK/CVS-111026(1) | January 2013

Management of AF

• Prevention of thromboembolism Antithrombotic therapy recommended for all patients

with AF, except in those patients at low risk, e.g. age <65 years and lone AF, or if contraindicated

• Relief of symptoms Symptom relief can be achieved by either controlling

the heart rate (rate-control) or restoring normal sinus rhythm (rhythm-control)

Choice between a rate-control or rhythm-control strategy depends on individual patient characteristics

2012 focused update of the ESC Guidelines for the management of atrial fibrillation.ESC Guidelines for the management of atrial fibrillation 2010.National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

UK/CVS-111026(1) | January 2013

Objectives of rate-control and rhythm-control strategies• Rate control:

Control the heart rate Relieve symptoms Prevention of tachycardia-induced cardiomyopathy

• Rhythm control: Re-establish normal sinus rhythm Synchronize atrial and ventricular contraction Relieve symptoms of AF

• Rhythm control might be expected to be the best treatment option as it corrects the underlying arrhythmia

• However, while rate-control does not address atrial arrhythmia, it has been shown to be at least as effective as rhythm-control in terms of improvements in mortality, stroke rate, symptoms of AF and quality of life1–3

Anti-arrhythmic agents used for rhythm-control have limitations, including drug-induced pro-arrhythmia and extra-cardiac side effects41. Wyse DG et al. N Engl J Med 2002;347:1825–33; 2. Hohnloser SH et al. Lancet

2000;356:1789–94. 3. Van Gelder IC et al. N Engl J Med 2002;347:1834–40; 4. ESC Guidelines for the management of atrial fibrillation 2010.

UK/CVS-111026(1) | January 2013

Anti-arrhythmic drugs

– Class IA

– Class IC– Class III

MAINTENANCE OF SINUS RHYTHM

Treatment options for AF

Adapted from Prystowsky EN. Am J Cardiol 2000;85:3D–11D.

CONTROL OF HEART RATESTROKE PREVENTION

-blockers Calcium channel blockers

(non-DHP) Digoxin

Vitamin K antagonists(e.g. warfarin)

Aspirin Clopidogrel Dabigatran etexilate Rivaroxaban Apixaban

PHARMACOLOGICAL PHARMACOLOGICALPHARMACOLOGICAL

Ablation Surgery (MAZE

procedure)

Ablation/permanent pacing Removal/isolation of left atrial appendage

NON-PHARMACOLOGICAL NON-PHARMACOLOGICALNON-PHARMACOLOGICAL

DHP = dihydropyridine


Treatment guidelines:recommendations

UK/CVS-111026(1) | January 2013

Treatment guidelines for stroke prevention in AF (1)

• Patients stratified into High, Medium and Low risk categories

• High risk: oral anticoagulation with warfarin, or aspirin if contraindicated

• Medium risk: consider anticoagulation with warfarin, or aspirin

• Low risk: aspirin 75–300 mg/day if no contraindications

• Oral anticoagulation recommended for all patients with AF, except those at low risk or with contraindications

• Stroke risk stratification using CHADS2 or CHA2DS2-VASc

• Oral anticoagulation preferred to aspirin in AF patients with one or more stroke risk factors

• No antithrombotic therapy recommended, rather than aspirin, in patients with no risk factors

National Institute for Health and Clinical Excellence (NICE)

20061

European Society of Cardiology (ESC) 20102

Timeline: 2006 2010 continued...

1. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006. 2. ESC Guidelines for the management of atrial fibrillation 2010.

UK/CVS-111026(1) | January 2013

Treatment guidelines for stroke prevention in AF (2)

• Oral anticoagulation recommended for all patients with AF, except those at low risk (<65 years and lone AF) or with contraindications

• CHA2DS2-VASc score recommended for assessing stroke risk rather than CHADS2

• Where oral anticoagulation is recommended, one of the NOACs should be considered rather than dose-adjusted warfarin for most patients

• In patients with a CHA2DS2-VASc score of 0 who are at low risk, no antithrombotic therapy is recommended

• Use of aspirin limited to patients who refuse oral anticoagulation

• Oral anticoagulation recommended for all patients with AF, except those at low risk or with contraindications

• Oral anticoagulation rather than no therapy, aspirin or aspirin + clopidogrel in patients with one or more stroke risk factors

• Oral anticoagulation with dabigatran 150 mg b.d. rather than warfarin*

• Uses CHADS2 score as the principal approach for risk-based treatment recommendations

European Society of Cardiology (ESC) focused update 20122

American College of Chest Physicians (ACCP) 20121

timeline continued... 2012

1. You JY et al. Chest 2012;141;e531S–e575S. 2. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

* NB: dabigatran was the only approved NOAC in this indication in the USA at the time the ACCP made its recommendations


European Society of Cardiology (ESC) clinical practice guidelines 2010 and 2012 focused updateManagement of atrial fibrillation

UK/CVS-111026(1) | January 2013

Factors influencing the choice of management strategyThe choice of management strategy should be tailored to the

patient based on a range of factors

• Antithrombotic therapy Risk factors for stroke/thromboembolism Risk factors for bleeding Net clinical benefit

• Rate-control vs rhythm-control Type and severity of symptoms Duration and type of AF Patient age Previous therapies/duration

of therapy

2012 focused update of the ESC Guidelines for the management of atrial fibrillation.ESC Guidelines for the management of atrial fibrillation 2010.National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

Left atrial diameter/left atrial appendage flow velocity

Other medical conditions, particularly cardiovascular disease

Concomitant therapies


European Society of Cardiology (ESC) Rate control vs rhythm control

UK/CVS-111026(1) | January 2013

ESC guidelines: rate control vs rhythm control• Strategy needs to be individualised, based on a careful

consideration of the likely benefits and risks for each patient

• Restoration of sinus rhythm is an important determinant of outcome, but the potential benefits of rhythm-control are often offset by the limited efficacy and adverse events of existing anti-arrhythmic agents

• All patients with one major stroke risk factor require anticoagulation, even if in normal sinus rhythm

• Rate-control is a reasonable strategy in elderly patients with minimal AF symptoms

• Factors favouring a rhythm-control strategy include: Younger age Troublesome symptoms despite rate control

ESC Guidelines for the management of atrial fibrillation 2010.

UK/CVS-111026(1) | January 2013

Management cascade for patients with AF

Anticoagulationissues

Assess TE Risk

Rate and rhythm control

Treatment of underlying disease ‘Upstream’

therapy

Record 12-lead ECG

AF-type symptoms

Consider referral

ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thromboembolism

ACEIs/ARBs Statins/PUFAs Others

Rate control±Rhythm control Antiarrhythmic drugs Ablation

Atrial fibrillation

Oral anticoagulant AspirinNone

PresentationEHRA scoreAssociated diseaseInitial assessment

ESC Guidelines for the management of atrial fibrillation 2010.


European Society of Cardiology (ESC) Stroke prevention

UK/CVS-111026(1) | January 2013

ESC guidelines 2012: stroke risk assessmentCHADS2 vs CHA2DS2-VASc

• ‘The 2010 ESC Guidelines on AF de-emphasised the use of the artificial low-, moderate-, and high-risk strata and recommended a risk factor-based approach defining ‘major’ and ‘clinically relevant non-major’ risk factors, which can be expressed as an acronym, CHA2DS2-VASc’

• ‘Whilst the CHADS2 score is simple, most now agree that it does not include many common stroke risk factors and its limitations have been highlighted’

• ‘The CHA2DS2-VASc score has since been validated in multiple cohorts; the accumulated evidence shows that CHA2DS2-VASc is better at identifying ‘truly low-risk’ patients with AF and is as good as, and possibly better than, scores such as CHADS2 in identifying patients who develop stroke and thromboembolism’

2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

UK/CVS-111026(1) | January 2013

• ESC focused update strongly recommends a practice shift towards identification of ‘truly low risk’ patients with AF (i.e. age <65 years and lone AF) who do not need antithrombotic therapy

• CHADS2 does not reliably identify ‘truly low risk’ patients

• CHA2DS2-VASc:

inclusive of the most common stroke risk factors

validated in multiple cohorts

better than CHADS2 at identifying ‘truly low risk’ patients

as good as CHADS2 in identifying patients who develop stroke and thromboembolism


ESC guidelines 2012: stroke risk assessmentCHADS2 vs CHA2DS2-VASc

UK/CVS-111026(1) | January 2013

Stroke risk assessment with CHADS2

CHADS2 criteria Score

Congestive heart failure 1

Hypertension 1

Age ≥75 yrs 1

Diabetes mellitus 1

Stroke/transient ischaemic attack

2

CHADS2total score

Risk of stroke (%/year) (95% CI)*

0 1.9 (1.2–3.0)

1 2.8 (2.0–3.8)

2 4.0 (3.1–5.1)

3 5.9 (4.6–7.3)

4 8.5 (6.3–11.1)

5 12.5 (8.2–17.5)

6 18.2 (10.5–27.4)

Gage BF et al. JAMA 2001;285:2864–70.

*Adjusted stroke rate = expected stroke rate per 100 patient-years based on exponential survival model, assuming aspirin not taken

UK/CVS-111026(1) | January 2013

Stroke risk assessment with CHA2DS2-VASc

CHA2DS2-VASc criteria Score

Congestive heart failure/left ventricular dysfunction

1

Hypertension 1

Age 75 yrs 2

Diabetes mellitus 1

Stroke/transient ischaemic attack/TE

2

Vascular disease(prior myocardial infarction, peripheral artery disease or aortic plaque)

1

Age 65–74 yrs 1

Sex category (i.e. female gender)

1

CHA2DS2-VASc

total score

Stroke & TE event rate at 1 year follow

up (%)*

0 0.78

1 2.01

2 3.71

3 5.92

4 9.27

5 15.26

6 19.74

7 21.50

8 22.38

9 23.64

*Without anticoagulation therapy. Actual rates of stroke in contemporary cohorts may vary from these estimates.

Lip GYF et al. Stroke 2010;41:2731-2738; Olesen J et al. BMJ 2011;342:d124.

TE = thromboembolism (includes peripheral artery embolism, ischaemic stroke, and pulmonary embolism)

UK/CVS-111026(1) | January 2013

ESC guidelines 2012 – bleeding risk assessmentusing HAS-BLED• ESC guidelines recommend HAS-BLED (hypertension,

abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly (>65), drugs/alcohol concomitantly) as a simple bleeding risk assessment score

• ‘A formal bleeding risk assessment is recommended for all patients with AF and, in patients with a HAS-BLED score ≥3, caution and regular review are appropriate, as well as efforts to correct the potentially reversible risk factors for bleeding’

• ‘The HAS-BLED score per se should not be used to exclude patients from OAC therapy but allows clinicians to make an informed assessment of bleeding risk’


UK/CVS-111026(1) | January 2013

• ESC = European Society of Cardiology; ICH = intracranial haemorrhage; OAC = oral anticoagulation

• HAS-BLED score: allows clinicians to make informed assessment of

bleeding risk makes clinicians think of the correctable risk factors

for bleeding has been validated in several independent cohorts correlates well with ICH risk


ESC guidelines 2012 – bleeding risk assessmentusing HAS-BLED

UK/CVS-111026(1) | January 2013

Clinical characteristics comprising the HAS-BLED bleeding risk score

HAS-BLED risk criteriaPoints

awarded

Hypertension 1

Abnormal renal and liver function (1 point each)

1 or 2

Stroke 1

Bleeding 1

Labile INRs 1

Elderly (e.g. age >65 years) 1

Drugs or alcohol (1 point each) 1 or 2

Maximum 9 points

ESC Guidelines for the management of atrial fibrillation 2010.Adapted from Pisters R et al. Chest 2010 Nov;138(5):1093-100.

INR = international normalised ratio

UK/CVS-111026(1) | January 2013

ESC focused update: general recommendations (1)

• 2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

RecommendationClas

sLeve

l

Antithrombotic therapy to prevent thromboembolism is recommended for all patients with AF, except those (both male and female) who are at low risk (aged <65 years and lone AF), or with contraindications

I A

Choice of antithrombotic therapy should be based upon the absolute risks of stroke/thromboembolism and bleeding and the net clinical benefit for a given patient

I A

CHA2DS2-VASc score is recommended as a means of assessing stroke risk in nonvalvular AF

I A

In patients with a CHA2DS2-VASc score of 0 (i.e. aged <65 years with lone AF) who are at low risk, with none of the risk factors, no antithrombotic therapy is recommended

I B

Class of recommendation I = evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Level of evidence A = Data derived from multiple randomised clinical trials or meta-analyses; B = Data derived from a single randomised clinical trial or large non-randomised studies.

UK/CVS-111026(1) | January 2013

• INR = international normalised ratio; OAC = oral anticoagulation; VKA = vitamin K antagonist

• Class of recommendation I = evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Class of recommendation; IIa = Weight of evidence/opinion is in favour of usefulness/efficacy. Level of evidence A = Data derived from multiple randomised clinical trials or meta-analyses.

RecommendationClas

sLeve

l

In patients with CHA2DS2-VASc score ≥2, OAC therapy with:

• a dose-adjusted VKA (INR 2–3); or• a direct thrombin inhibitor (dabigatran); or• an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban)… is recommended unless contraindicated

I A

In patients with CHA2DS2-VASc score 1, OAC therapy with:• a dose-adjusted VKA (INR 2–3); or• a direct thrombin inhibitor (dabigatran); or• an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban)… should be considered, based upon an assessment of the risk of bleeding complications and patient preferences

IIa A



UK/CVS-111026(1) | January 2013

• NOAC = novel oral anticoagulant; OAC = oral anticoagulation; VKA = vitamin K antagonist;

• Class of recommendation IIa = Weight of evidence/opinion is in favour of usefulness/efficacy. Level of evidence B = Data derived from a single randomised clinical trial or large non-randomised studies.

RecommendationClas

sLeve

l

Female patients who are aged <65 years and have lone AF (but still have a CHA2DS2-VASc score of 1 by virtue of their gender) are low risk and no antithrombotic therapy should be considered

IIa B

When patients refuse the use of any OAC (whether VKA or NOACs), antiplatelet therapy should be considered using combination therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily (where there is a low risk of bleeding) or – less effectively – aspirin 75–325 mg daily

IIa B



UK/CVS-111026(1) | January 2013

ESC guidelines for antithrombotic therapy in AFRisk category CHA2DS2-VASc

score Recommended therapy

One ‘major’ risk factor or 2 ‘clinically relevant non-major’ risk factors

2 OAC* therapy is recommended unless contraindicated

One ‘clinically relevantnon-major’ risk factor 1

OAC therapy should be considered, based upon an assessment of the risk of bleeding and patient preferences

No risk factors 0 No antithrombotic therapy


*OAC therapy: dose-adjusted VKA (INR 2-3), or a direct thrombin inhibitor (dabigatran), or an oral Factor Xa inhibitor (rivaroxaban or apixaban)

OAC = oral anticoagulant; VKA = vitamin K antagonist

UK/CVS-111026(1) | January 2013

Antiplatelet therapy with aspirin plus clopidogrel or – less effectively – aspirin only, should be considered in patients who refuse any OAC or cannot tolerate anticoagulation for reasons unrelated to bleeding. If there are contraindications to OAC or antiplatelet therapy, left atrial appendage occlusion, closure or excision may be considered.*Includes rheumatic valvular disease and prosthetic valves; NOAC = novel oral anticoagulant; VKA = vitamin K antagonist


Assess bleeding risk (HAS-BLED score)

Consider patient values and preferences

Yes

ATRIAL FIBRILLATION

Valvular AF*

<65 years and lone AF (including females)

Assess risk of strokeCHA2DS2-VASc score

No antithrombotictherapy NOAC VKA

0 1

No (i.e. non-valvular)

Yes

No

≥2

Oral anticoagulant therapy

CHA2DS2-VASc score:

= 0 = 1 = ≥2

Treatment option:

= best option = alternative option

Oral anticoagulation for stroke prevention in AF

UK/CVS-111026(1) | January 2013

ESC guidelines: use of VKAs and antiplatelets

• Stroke prevention with a VKA is effective when TTR is good

‘Well-controlled’ VKA therapy defined as a TTR of at least 70%

• When a VKA is used, efforts to improve the quality of INR control are needed in order to achieve high TTRs

• Efficacy of stroke prevention with aspirin is weak, with potential for harm

Risk of major bleeding and ICH not significantly different to that of OAC, especially in the elderly

• Antiplatelets for stroke prevention in AF should be limited to patients who refuse any form of OAC

• ICH = intracranial haemorrhage INR = international normalised ratio; OAC = oral anticoagulation; TTR = time in therapeutic range; VKA = vitamin K antagonist


UK/CVS-111026(1) | January 2013

ESC guidelines: aspirin

• ‘Antiplatelet therapy for stroke prevention in AF should be limited to patients who refuse any form of OAC or cannot tolerate anticoagulation for reasons unrelated to bleeding’

• ‘When patients refuse the use of an OAC (whether VKA or NOACs) antiplatelet therapy should be considered, using combination therapy with aspirin 75-100 mg plus clopidogrel 75 mg daily (where there is a low risk of bleeding) or – less effectively – aspirin 75-325 mg daily’


UK/CVS-111026(1) | January 2013

ESC guidelines: NOACs vs VKAs

• NOACs offer better efficacy, safety and convenience compared with OAC therapy with VKAs

• Where an OAC is recommended, one of the NOACs – either a direct thrombin inhibitor (dabigatran) or an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban) should be considered instead of adjusted-dose VKA (INR 2–3) in most patients with AF

• INR = international normalised ratio; NOAC = novel oral anticoagulant; VKA = vitamin K antagonist


UK/CVS-111026(1) | January 2013

ESC guidelines: NOAC-specific recommendations (1)

• INR = international normalised ratio; NOAC = novel oral anticoagulant; VKA = vitamin K antagonist

• Class of recommendation I = evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective; IIa = Weight of evidence/opinion is in favour of usefulness/efficacy. Level of evidence A = Data derived from multiple randomised clinical trials or meta-analyses; B = Data derived from a single randomised clinical trial or large non-randomised studies.


RecommendationClas

sLeve

l

When adjusted-dose VKA (INR 2–3) cannot be used in a patient with AF where an OAC is recommended due to difficulties in keeping within therapeutic anticoagulation, experiencing side effects of VKAs, or inability to attend/undertake INR monitoring, one of the NOACs, either:

• a direct thrombin inhibitor (dabigatran); or• an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban)… is recommended

I B

When an OAC is recommended, one of the NOACs, either:• a direct thrombin inhibitor (dabigatran); or• an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban)… should be considered rather than adjusted-dose VKA

(INR 2–3) for most patients with nonvalvular AF, based on their net clinical benefit

IIa A

UK/CVS-111026(1) | January 2013

ESC guidelines: NOAC-specific recommendations (2)

• BID = twice daily; CrCl = creatinine clearance; OD = once daily

• Class of recommendation IIa = Weight of evidence/opinion is in favour of usefulness/efficacy. Level of evidence B = Data derived from a single randomised clinical trial or large non-randomised studies; C = Consensus of opinion of the experts and/or small studies, retrospective studies, registries.


RecommendationClas

sLeve

l

When dabigatran is prescribed, a dose of 150 mg BID should be considered for most patients in preference to 110 mg BID, with the latter dose recommended in:•elderly patients, age ≥80 years•concomitant use of interacting drugs (e.g. verapamil)•high bleeding risk (HAS-BLED score ≥3)•moderate renal impairment (CrCl 30–49 mL/min)

IIa B

Where rivaroxaban is being considered, a dose of 20 mg OD should be considered for most patients in preference to 15 mg OD, with the latter dose recommended in:•high bleeding risk (HAS-BLED ≥3)•moderate renal impairment (CrCl 30–49 mL/min)

IIa C

UK/CVS-111026(1) | January 2013

ESC guidelines: NOACs in patients with renal impairment

• CrCl = creatinine clearance; NOAC = novel oral anticoagulant

• Class of recommendation IIa = Weight of evidence/opinion is in favour of usefulness/efficacy; III = Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful. Level of evidence A = Data derived from multiple randomised clinical trials or meta-analyses; B = Data derived from a single randomised clinical trial or large non-randomised studies.


Recommendation ClassLeve

l

Baseline and subsequent regular assessment of renal function (by CrCl) is recommended in patients following initiation of any NOAC, which should be done annually but more frequently in those with moderate renal impairment, where CrCl should be assessed 2–3 times per year

IIa B

NOACs (dabigatran, rivaroxaban, and apixaban) are not recommended in patients with severe renal impairment (CrCl <30 mL/min)

III A


European Society of Cardiology (ESC) Bleeding recommendations

UK/CVS-111026(1) | January 2013

ESC guidelines: bleeding recommendations

• NOAC = novel oral anticoagulant; NSAIDs = non-steroidal anti-inflammatory drugs; OAC = oral anticoagulation; VKA = vitamin K antagonist

• Class of recommendation I = evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective; IIa = Weight of evidence/opinion is in favour of usefulness/efficacy. Level of evidence A = Data derived from multiple randomised clinical trials or meta-analyses; B = Data derived from a single randomised clinical trial or large non-randomised studies.


RecommendationClas

sLeve

l

Assessment of bleeding risk is recommended when prescribing antithrombotic therapy (whether with VKA, NOAC, aspirin/clopidogrel, or aspirin alone)

I A

HAS-BLED score should be considered as a calculation to assess bleeding risk, whereby a score ≥3 indicates ‘high risk’ and some caution and regular review is needed, following initiation of antithrombotic therapy, whether with OAC or antiplatelet therapy

Correctable factors for bleeding (e.g. uncontrolled blood pressure, labile INRs if patient was on a VKA, concomitant drugs [aspirin, NSAIDs, etc.], alcohol, etc.) should be addressed

Use of the HAS-BLED score should be used to identify modifiable bleeding risks that need to be addressed, but should not be used on its own to exclude patients from OAC therapy

IIa

A

B

B

Risk of major bleeding with antiplatelet therapy (with aspirin–clopidogrel combination therapy and – especially in the elderly – also with aspirin monotherapy) should be considered as being similar to OAC

IIa B

UK/CVS-111026(1) | January 2013

• ESC = European Society of Cardiology; ICH = intracranial haemorrhage; OAC = oral anticoagulation

• HAS-BLED score: allows clinicians to make informed assessment of

bleeding risk makes clinicians think of the correctable risk factors

for bleeding has been validated in several independent cohorts correlates well with ICH risk

• High HAS-BLED score per se should not be used to exclude patients from OAC therapy


ESC guidelines 2012 – bleeding risk assessmentusing HAS-BLED

UK/CVS-111026(1) | January 2013

ESC guidelines: management of bleeding

37

• *With dabigatran• aPTT = activated partial thromboplastin time; NOAC

= novel oral anticoagulant: PCC = prothrombin complex concentrate; PT = prothrombin time; rVFVII = activated recombinant Factor VIIa


Patient on NOAC presenting with bleeding

Check haemodynamic status, basic coagulation tests, to assess anticoagulation effect (e.g. aPTT for dabigatran, PT or anti-Xa activity for rivaroxaban), renal function, etc.

Minor

Moderate-to-severe

Very severe Consider rFVIIa or PCC

Charcoal filtration*/haemodialysis*

Delay next dose or discontinue treatment

Symptomatic/supportive treatment

Mechanical compression

Fluid replacement

Blood transfusion

Oral charcoal if recently ingested*


European Society of Cardiology (ESC) Special situations

UK/CVS-111026(1) | January 2013

ESC guidelines: cardioversion recommendations

• INR = international normalised ratio; NOAC = novel oral anticoagulant; OAC = oral anticoagulation; VKA = vitamin K antagonist;

• Class of recommendation I = evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Level of evidence B = Data derived from a single randomised clinical trial or large non-randomised studies.


RecommendationClas

sLeve

l

For patients with AF of ≥48 hour duration, or when the duration of AF is unknown, OAC therapy (e.g. VKA with INR 2–3 or dabigatran) is recommended for ≥3 weeks prior to and for ≥4 weeks after cardioversion, regardless of the method (electrical or oral/i.v. pharmacological)

I B

In patients with risk factors for stroke or AF recurrence, OAC therapy, whether with dose-adjusted VKA (INR 2–3) or a NOAC, should be continued lifelong irrespective of the apparent maintenance of sinus rhythm following cardioversion

I B

UK/CVS-111026(1) | January 2013

ESC guidelines: summary of 2012 update

• Emphasises use of CHA2DS2-VASc score to identify ‘truly low risk’ patients who do not need antithrombotic therapy

• NOACs broadly preferable to VKA in the vast majority of patients with nonvalvular AF

• Aspirin for stroke prevention should be limited to patients who refuse any form of OAC

• NOAC = novel oral anticoagulant; OAC = oral anticoagulation; VKA = vitamin K antagonist



NICE clinical guideline 36 (2006) Atrial fibrillation: national clinical guideline for management in primary and secondary care


NICE stroke risk stratification algorithm (1)

National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

Patients with paroxysmal, persistent or permanent AF

Determine stroke/thromboembolic risk

• Previous ischaemic stroke/TIA or thromboembolic event

• Age ≥75 yrs with hypertension, diabetes or vascular disease*

• Clinical evidence of valve disease, heart failure or impaired LV function on echocardiography†

• Age ≥65 yrs with no high-risk factors

• Age <75 yrs with hypertension, diabetes or vascular disease*

• Age <65 yrs with no moderate- or high-risk factors

*Coronary artery disease or peripheral artery disease; †An echocardiogram is not needed for routine assessment, but refines clinical risk stratification in the case of moderate or severe left dysfunction and valve disease; LV = left ventricular; NICE = National Institute for Health and Clinical Excellence; TIA = transient ischaemic attack

High risk Moderate risk Low risk


NICE stroke risk stratification algorithm (2)

High risk Moderate risk Low risk

Anticoagulationwith warfarin

Consideranticoagulation

or aspirin*

Aspirin 75–300 mg/day

if no contraindications

Contraindications to warfarin?

Warfarin, target INR 2.5 (range 2.0–3.0)

Reassess risk stratification

whenever individual risk factors

are reviewed*Treatment may be decided on an individual basis, and the physician must balance the risk and benefits of warfarin vs aspirin; INR = international normalised ratio; NICE = National Institute for Health and Clinical Excellence

Yes

No

National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

UK/CVS-111026(1) | January 2013

Rate-control vs rhythm-control:NICE treatment strategy decision tree

Confirmed diagnosis of AF

Further investigations and clinical assessment includingrisk stratification for stroke/thromboembolism

Paroxysmal AF Persistent AF Permanent AF

OR

Rhythm-control Rate-controlRemains symptomatic

Failure of rhythm-control

NICE = National Institute for Health and Clinical ExcellenceNational Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.


American College of Chest Physicians (ACCP) clinical practice guidelines 2012Antithrombotic therapy for atrial fibrillation

UK/CVS-111026(1) | January 2013

2012 ACCP guidelines for antithrombotic therapy in patients with AF

Patient features Recommended antithrombotic therapy

Low risk of stroke

(e.g. CHADS2 = 0)

None rather than antithrombotic therapy

Intermediate risk

of stroke(e.g. CHADS2 = 1)

OAC rather than no therapy, aspirin, or aspirin + clopidogrel

- dabigatran 150 mg b.d.* rather than dose-adjusted VKA†

High risk of stroke(e.g. CHADS2 = 2)

OAC rather than no therapy, aspirin, or aspirin + clopidogrel


Previous stroke/TIA OAC rather than no therapy, aspirin, or aspirin + clopidogrel


* NB: ACCP made recommendations only in respect of treatments approved in the USA at the time of review. Other NOACs were not approved for this indication at that time.

• You JY et al. Chest 2012;141;e531S–e575S.

† Target range for international normalised ratio: 2.0–3.0

b.d. = twice daily; OAC = oral anticoagulant; TIA = transient ischaemic attack; VKA = vitamin K antagonist


Treatment guidelines summaries

UK/CVS-111026(1) | January 2013

Warfarin in treatment guidelines: summary

• Warfarin has demonstrated marked efficacy vs placebo in reducing stroke in patients with AF

• In trials, warfarin has been shown to be more effective than aspirin or dual antiplatelet therapy in reducing stroke in patients with AF

• ESC focused update states novel OACs broadly preferable to warfarin in the vast majority of patients with nonvalvular AF

ESC = European Society of Cardiology; OAC = oral anticoagulant

UK/CVS-111026(1) | January 2013

Aspirin in treatment guidelines: summary

• Aspirin is a convenient option for routine clinical practice, but it provides insufficient protection for stroke prevention in high-risk patients

• Older guidelines for atrial fibrillation have recommended aspirin as an option for patients at low risk or contraindicated to warfarin

• Latest ESC guidelines for atrial fibrillation limit antiplatelet therapy to patients who refuse any form of OAC or cannot tolerate anticoagulation for reasons unrelated to bleeding

• In patients with no risk factors, no antithrombotic therapy is recommended

ESC = European Society of Cardiology; OAC = oral anticoagulant

UK/CVS-111026(1) | January 2013

Novel OACs in treatment guidelines: summary• Latest ESC focused update states novel OACs broadly

preferable to warfarin in the vast majority of patients with nonvalvular AF

• Latest ACCP guidelines recommend dabigatran 150 mg b.d. rather than adjusted-dose VKA therapy in patients with AF at intermediate to high risk of stroke.

NB: ACCP made recommendations only in respect of treatments approved in the USA at the time of review. Other NOACs were not approved for this indication at that time

Rivaroxaban and apixaban are also licensed in SPAF and can also be considered as an option for oral anticoagulation. Please refer to SPC before prescribing




UK/CVS-111026(1) | January 2013

• An educational pack has been developed to support the prescribing of dabigatran etexilate for stroke prevention in nonvalvular atrial fibrillation

• Go to www.pradaxa.co.uk where you will be able to download the Pradaxa® Educational Pack

• The pack contains:– Prescriber guide

– Summaries of Product Characteristics (SPC)

– Patient alert card

• To order a copy, call the Pradaxa® information line on 0845 601 7880

• Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (Freephone)

Dabigatran etexilate – educational pack and prescriber guide and adverse event reporting

51Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:Pradaxa 150 mg: http://www.medicines.org.uk/EMC/medicine/24839/SPCPradaxa 110 mg: http://www.medicines.org.uk/EMC/medicine/20760/SPC

UK/CVS-111026(1) | January 2013

• A prescriber guide has been developed to support the prescribing of rivaroxaban for stroke prevention in nonvalvular atrial fibrillation

• Go to www.xarelto.co.uk to download the following: – Prescriber guide



• Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard

• Adverse events should be also be reported to Bayer plc, on tel: 01635 563500, fax: 01635 563703, email: [email protected]

Rivaroxaban – prescriber guide and adverse event reporting

52Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at: Xarelto 20 mg: http://www.medicines.org.uk/EMC/medicine/25586/SPCXarelto 15 mg: http://www.medicines.org.uk/EMC/medicine/25592/SPC

UK/CVS-111026(1) | January 2013

• A prescriber guide has been developed to support the prescribing of apixaban for stroke prevention in nonvalvular atrial fibrillation

• Go to www.eliquis.co.uk to download the following: – Prescriber guide



• Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard

• Adverse events should also be reported to Bristol-Myers Squibb Pharmaceuticals Ltd, Medical Information on 0800 731 1736, email: [email protected]

Apixaban – prescriber guide and adverse event reporting

53Summary of Product Characteristics for apixaban (Eliquis® ) can be found at: Eliquis 5.0 mg: http://www.medicines.org.uk/EMC/medicine/27220/SPCEliquis 2.5 mg: http://www.medicines.org.uk/EMC/medicine/24988/SPC

Documents

UK/CVS-111026(1) | January 2013 Stroke Prevention in Atrial Fibrillation Treatment guidelines: Developed and funded by UK/CVS-111026(1) | Date of preparation: