1. Stroke Prevention in Atrial Fibrillation Treatment guidelines:
Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:
Pradaxa 150 mg:
Pradaxa 110 mg:
Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at:
Xarelto 20 mg:
Xarelto 15 mg:
Developed and funded by
Summary of Product Characteristics for apixaban (Eliquis® ) can be found at:
Eliquis 5.0 mg:
Eliquis 2.5 mg:
UK/CVS (1) | Date of preparation: January 2013 1

2. Stroke Prevention in Atrial Fibrillation Treatment guidelines:
Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:
Pradaxa 150 mg:
Pradaxa 110 mg:
Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at:
Xarelto 20 mg:
Xarelto 15 mg:
Summary of Product Characteristics for apixaban (Eliquis® ) can be found at:
Eliquis 5.0 mg:
Eliquis 2.5 mg: 2

3. Goals of management of AF
Management of AF has two broad objectives:
Prevention of complications, including thromboembolism (particularly stroke) and heart failure
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. 3

4. Management of AF Prevention of thromboembolism Relief of symptoms
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. 4

5. Objectives of rate-control and rhythm-control strategies
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 effects4
1. Wyse DG et al. N Engl J Med 2002;347:1825–33; 2. Hohnloser SH et al. Lancet 2000;356:1789– Van Gelder IC et al. N Engl J Med 2002;347:1834–40; ESC Guidelines for the management of atrial fibrillation 2010. 5

6. Treatment options for AF
STROKE PREVENTION
CONTROL OF HEART RATE
MAINTENANCE OF SINUS RHYTHM
PHARMACOLOGICAL
PHARMACOLOGICAL
PHARMACOLOGICAL
Vitamin K antagonists (e.g. warfarin)
Aspirin
Clopidogrel
Dabigatran etexilate
Rivaroxaban
Apixaban
-blockers
Calcium channel blockers (non-DHP)
Digoxin
Anti-arrhythmic drugs
– Class IA
– Class IC – Class III
NON-PHARMACOLOGICAL
NON-PHARMACOLOGICAL
NON-PHARMACOLOGICAL
Removal/isolation of left atrial appendage
Ablation/permanent pacing
Ablation
Surgery (MAZE procedure)
DHP = dihydropyridine
Adapted from Prystowsky EN. Am J Cardiol 2000;85:3D–11D. 6

7. Treatment guidelines: recommendations7

8. Treatment guidelines for stroke prevention in AF (1)
Timeline:
continued...
National Institute for Health and Clinical Excellence (NICE) 20061
European Society of Cardiology (ESC) 20102
• 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
1. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, ESC Guidelines for the management of atrial fibrillation 2010. 8

9. Treatment guidelines for stroke prevention in AF (2)
timeline continued
American College of Chest Physicians (ACCP) 20121
European Society of Cardiology (ESC) focused update 20122
• 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 mg b.d. rather than warfarin*
Uses CHADS2 score as the principal approach for risk-based treatment recommendations
• 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
* NB: dabigatran was the only approved
NOAC in this indication in the USA at the
time the ACCP made its recommendations
1. You JY et al. Chest 2012;141;e531S–e575S.
focused update of the ESC Guidelines for the management of atrial fibrillation. 9

10. European Society of Cardiology (ESC) clinical practice guidelines 2010 and focused update Management of atrial fibrillation

11. Factors influencing the choice of management strategy
The 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
Left atrial diameter/left atrial appendage flow velocity
Other medical conditions, particularly cardiovascular disease
Concomitant therapies
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. 11

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

13. 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.

14. Management cascade for patients with AF
Atrial fibrillation
Record 12-lead ECG
Presentation
EHRA score
Associated disease
Initial assessment
Anticoagulation issues
Assess TE Risk
Oral anticoagulant Aspirin
None
Rate and rhythm control
AF-type symptoms
Rate control
±Rhythm control Antiarrhythmic drugs Ablation
Treatment of underlying disease ‘Upstream’ therapy
Consider referral
ACEIs/ARBs Statins/PUFAs Others
ESC Guidelines for the management of atrial fibrillation 2010.
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thromboembolism

15. European Society of Cardiology (ESC) Stroke prevention

16. ESC guidelines 2012: stroke risk assessment CHADS2 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.

17. ESC guidelines 2012: stroke risk assessment CHADS2 vs CHA2DS2-VASc
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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 17

18. Stroke risk assessment with CHADS2
CHADS2 criteria
Score
Congestive heart failure 1
Hypertension
Age ≥75 yrs
Diabetes mellitus
Stroke/transient ischaemic attack 2
CHADS2 total score
Risk of stroke (%/year) (95% CI)*
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)
*Adjusted stroke rate = expected stroke rate per 100 patient-years based on exponential survival model, assuming aspirin not taken
Gage BF et al. JAMA 2001;285:2864–70.

19. Stroke risk assessment with CHA2DS2-VASc
CHA2DS2-VASc criteria
Score
Congestive heart failure/ left ventricular dysfunction 1
Hypertension
Age 75 yrs 2
Diabetes mellitus
Stroke/transient ischaemic attack/TE
Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque)
Age 65–74 yrs
Sex category (i.e. female gender)
CHA2DS2-VASc total score
Stroke & TE event rate at 1 year follow up (%)*
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
TE = thromboembolism (includes peripheral artery embolism, ischaemic stroke, and pulmonary embolism)
*Without anticoagulation therapy. Actual rates of stroke in contemporary cohorts may vary from these estimates.
Lip GYF et al. Stroke 2010;41: ; Olesen J et al. BMJ 2011;342:d124.

20. ESC guidelines 2012 – bleeding risk assessment using 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’
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

21. ESC guidelines 2012 – bleeding risk assessment using HAS-BLED
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 = European Society of Cardiology; ICH = intracranial haemorrhage; OAC = oral anticoagulation
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 21

22. Clinical characteristics comprising the HAS-BLED bleeding risk score
HAS-BLED risk criteria
Points awarded
Hypertension 1
Abnormal renal and liver function (1 point each)
1 or 2
Stroke
Bleeding
Labile INRs
Elderly (e.g. age >65 years)
Drugs or alcohol (1 point each)
Maximum 9 points
INR = international normalised ratio
ESC Guidelines for the management of atrial fibrillation 2010.
Adapted from Pisters R et al. Chest 2010 Nov;138(5):

23. ESC focused update: general recommendations (1)
Class
Level
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
CHA2DS2-VASc score is recommended as a means of assessing stroke risk in nonvalvular AF
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 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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

24. ESC focused update: general recommendations (2)
Class
Level
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:
… should be considered, based upon an assessment of the risk of bleeding complications and patient preferences
IIa
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

25. ESC focused update: general recommendations (3)
Class
Level
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
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

26. ESC guidelines for antithrombotic therapy in AF
Risk 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 relevant
non-major’ risk factor 1
OAC therapy should be considered, based upon an assessment of the risk of bleeding and patient preferences
No risk factors
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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 26

27. Oral anticoagulation for stroke prevention in AF
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 stroke CHA2DS2-VASc score
No antithrombotic therapy
NOAC
VKA 1
No (i.e. non-valvular) No ≥2
Oral anticoagulant therapy
CHA2DS2-VASc score:
= 0
= 1
= ≥2
Treatment option:
= best option
= alternative
option
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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 27

28. 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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

29. 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 mg plus clopidogrel 75 mg daily (where there is a low risk of bleeding) or – less effectively – aspirin mg daily’
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

30. 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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

31. ESC guidelines: NOAC-specific recommendations (1)
Class
Level
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:
… 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
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

32. ESC guidelines: NOAC-specific recommendations (2)
Class
Level
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) C
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

33. ESC guidelines: NOACs in patients with renal impairment
Recommendation
Class
Level
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
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

34. European Society of Cardiology (ESC) Bleeding recommendations34

35. ESC guidelines: bleeding recommendations
Class
Level
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 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
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 35

36. ESC guidelines 2012 – bleeding risk assessment using HAS-BLED
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 = European Society of Cardiology; ICH = intracranial haemorrhage; OAC = oral anticoagulation
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 36

37. Patient on NOAC presenting with bleeding
ESC guidelines: management of bleeding
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
Delay next dose or discontinue treatment
Symptomatic/supportive treatment
Mechanical compression
Fluid replacement
Blood transfusion
Oral charcoal if recently ingested*
Moderate-to-severe
Consider rFVIIa or PCC
Charcoal filtration*/haemodialysis*
Very severe
*With dabigatran
aPTT = activated partial thromboplastin time; NOAC = novel oral anticoagulant: PCC = prothrombin complex concentrate; PT = prothrombin time; rVFVII = activated recombinant Factor VIIa
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 37 37

38. European Society of Cardiology (ESC) Special situations38

39. ESC guidelines: cardioversion recommendations
Class
Level
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
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.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

40. 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
2012 focused update of the ESC Guidelines for the management of atrial fibrillation. 40

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

42. NICE stroke risk stratification algorithm (1)
Patients with paroxysmal, persistent or permanent AF
Determine stroke/thromboembolic risk
High risk
Moderate risk
Low 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
National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

43. NICE stroke risk stratification algorithm (2)
High risk
Moderate risk
Low risk
Anticoagulation with warfarin
Consider anticoagulation or aspirin*
Contraindications to warfarin?
Aspirin 75–300 mg/day if no contraindications
Yes No
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
National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

44. Rate-control vs rhythm-control: NICE treatment strategy decision tree
Confirmed diagnosis of AF
Further investigations and clinical assessment including risk stratification for stroke/thromboembolism
Paroxysmal AF
Persistent AF
Permanent AF OR
Rhythm-control
Remains symptomatic
Rate-control
Failure of rhythm-control
NICE = National Institute for Health and Clinical Excellence
National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006.

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

46. 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)
Previous stroke/TIA
* 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.
† 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
You JY et al. Chest 2012;141;e531S–e575S. 46

47. Treatment guidelines summaries47

48. 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 48

49. 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 49

50. 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
Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:
Pradaxa 150 mg:
Pradaxa 110 mg:
Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at:
Xarelto 20 mg:
Xarelto 15 mg:
Summary of Product Characteristics for apixaban (Eliquis® ) can be found at:
Eliquis 5.0 mg:
Eliquis 2.5 mg: 50

51. Dabigatran etexilate – educational pack and prescriber guide and adverse event reporting
An educational pack has been developed to support the prescribing of dabigatran etexilate for stroke prevention in nonvalvular atrial fibrillation
Go to 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
Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to Boehringer Ingelheim Drug Safety on (Freephone)
Summary of Product Characteristics for dabigatran etexilate (Pradaxa®) can be found at:
Pradaxa 150 mg:
Pradaxa 110 mg: 51

52. Rivaroxaban – prescriber guide and adverse event reporting
A prescriber guide has been developed to support the prescribing of rivaroxaban for stroke prevention in nonvalvular atrial fibrillation
Go to to download the following:
– Prescriber guide
– Summaries of Product Characteristics (SPC)
– Patient alert card
Adverse events should be reported. Reporting forms and information can be found at
Adverse events should be also be reported to Bayer plc, on tel: , fax: ,
Summary of Product Characteristics for rivaroxaban (Xarelto® ) can be found at:
Xarelto 20 mg:
Xarelto 15 mg: 52

53. Apixaban – prescriber guide and adverse event reporting
A prescriber guide has been developed to support the prescribing of apixaban for stroke prevention in nonvalvular atrial fibrillation
Go to to download the following:
– Prescriber guide
– Summaries of Product Characteristics (SPC)
– Patient alert card
Adverse events should be reported. Reporting forms and information can be found at
Adverse events should also be reported to Bristol-Myers Squibb Pharmaceuticals Ltd, Medical Information on ,
Summary of Product Characteristics for apixaban (Eliquis® ) can be found at:
Eliquis 5.0 mg:
Eliquis 2.5 mg: 53