THROMBOEMBOLI PREVENTION

IN ATRIAL FIBRILLATION
Budi Yuli Setianto
Department of Cardiology and Vascular
Medicine Faculty of Medicine Gadjah Mada
University/ Sardjito Hospital Yogyakarta

Atrial Fibrillation

Problems
1. Rate: tachycardia, palpitations
2. Lack of atrial contraction: thromboembolism/
stroke

Atrial Fibrillation and Stroke

Epidemiology
Atrial fibrillation is the most common
significant arrhythmia:
Atrial fibrillation prevalence is strongly agedependent
10% of age 80+ years1
Relative risk for stroke = 52

1. Go AS, et al. JAMA. 2001;285:2370-2375.

2. Wolf PA, et al. Arch Intern Med. 1987;147:1561-1564.

AF and Stroke
Framingham Study 30-Year Follow-Up*

*Adjusted for blood pressure.

Abbreviations: AF, atrial fibrillation; py, patient years; o, without atrial fibrillation; RR, relative risk.

Wolf PA, et al. Arch Intern Med. 1987;147:1561-1564.

Prevalence of Diagnosed Atrial Fibrillation by

Age and Gender

Go AS, et al. JAMA. 2001;285:2370-2375.

Lifetime Risk of Developing AF

Lifetime risk of developing atrial fibrillation
(AF) for men and women age 40 years and
older

Overall: about 1 in 4*

Lloyd-Jones D, et al. Circulation. 2004;110:1042-1046.

*Based primarily on white individuals.

Atrial Fibrillation
Putative Mechanism for Stroke

Anticoagulation for Atrial Fibrillation

For Whom?
Guideline perspective
Anticoagulate atrial fibrillation patients whose risk
of stroke is high enough to merit the burden
and risk of anticoagulant therapy
Aspirin or no antithrombotic treatment for others

Since published in 2010

in the ESC guidelines
Use of risk factor-based approach for risk stratification
of stroke, with a focus on:
identifying patients who are truly at low risk who do not
require antithrombotic therapy.
instead of focus on identifying high-risk patients.

Risk factors for ischemic stroke / TIA / systemic embolism in

patients with atrial fibrillation: the Swedish Atrial Fibrillation
cohort study

(Samardhi et al., 2011)

*Applies to persistent or paroxysmal AF.

CHADS2 score limitations

10% of screened patients included, and many risk factors for
stroke are inconsistently defined or not systematically
recorded.
For example, blood vessel disease (not included in the CHADS2 score),
whereas an independent risk factor for stroke in AF and significantly
improve the predictive ability CHADS2

The risk of stroke is also increased since age 65 years, with a greater
risk at age 75 years or older.

Many patients classified as low risk using the CHADS2 (score =

0) have a stroke rate >1.5%/ year
CHADS2 score = 0 is not trusted to identify AF patients truly at
low risk

which is defined as the risk factors of major and non-major clinically relevant

Stroke risk assessment: CHA2DS2-VASc

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
Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

HAS-BLED
HAS-BLED risk criteria

Hypertension

Abnormal renal or liver

function (1 point each)

Score
1
1 or 2

Stroke

Bleeding

Labile INRs

Elderly

(e.g. age >65 yrs)

Drugs or alcohol
(1 point each)

INR = international normalized ratio

1 or 2

HAS-BLED
total score

Number Bleeds per 100

of bleeds patient-yrs*

798

1.13

1286

13

1.02

744

14

1.88

187

3.74

46

8.70

12.5

0.0

*P value for trend = 0.007

Pisters R et al. Chest. 2010;138:1093100; ESC guidelines: Camm J et al. Eur Heart J 2010;31:2369429
17

Choice of anticoagulant
Atrial fibrillation

Yes

Valvular AF*
No (i.e. nonvalvular)
Yes

<65 years and lone AF (including females)

No
Assess risk of stroke
CHA2DS2-VASc score

2
Oral anticoagulant therapy

Assess bleeding risk

(HAS-BLED score)
Consider patient values and preferences
No antithrombotic
therapy

NOAC

VKA

Antiplatelet therapy with ASA plus clopidogrel or less effectively ASA 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
Colour CHA2DS2-VASc: green = 0, blue = 1, red 2; line: solid = best option; dashed = alternative option
*Includes rheumatic valvular disease and prosthetic valves; ASA = acetylsalicylic acid; NOAC = novel oral anticoagulant;
VKA = vitamin K antagonist
Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

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

Moderate-to-severe

Delay next dose or discontinue treatment

Symptomatic/supportive treatment
Mechanical compression
Fluid replacement
Blood transfusion

Oral charcoal if recently ingested*

Very severe

Consider rFVIIa or PCC

Charcoal filtration*/haemodialysis*

*With dabigatran
aPTT = activated partial thromboplastin time; NOAC = novel oral anticoagulant: PCC = prothrombin complex concentrate;
PT = prothrombin time; rVFVII = activated recombinant Factor VIIa
Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

No Standard Bleeding Definition

Recommendations for
antithrombotic therapy

General recommendations (1)

Recommendation

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

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

Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

General recommendations (2)

Recommendation
In patients with CHA2DS2-VASc score 2, OAC therapy with:
a dose-adjusted VKA (INR 23); or
a direct thrombin inhibitor (dabigatran); or
an oral Factor Xa inhibitor (e.g. rivaroxaban, apixaban*)
is recommended unless contraindicated

In patients with CHA2DS2-VASc score 1, OAC therapy with:

a dose-adjusted VKA (INR 23); 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

*Pending approval; INR = international normalized ratio; OAC = oral anticoagulation; VKA = vitamin K antagonist
Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

Class

Level

IIa

General recommendations (3)

Recommendation

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

When patients refuse the use of any OAC (whether VKA or NOACs),
antiplatelet therapy should be considered, using combination therapy
with ASA 75100 mg plus clopidogrel 75 mg daily (where there is a low
risk of bleeding) or less effectively ASA 75325 mg daily

IIa

ASA = acetylsalicylic acid; NOAC = novel oral anticoagulant; OAC = oral anticoagulation; VKA = vitamin K antagonist; Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

NOAC-specific recommendations (1)

Recommendation
When adjusted-dose VKA (INR 23) 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
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 23) for most patients with nonvalvular AF, based on their
net clinical benefit

Class

Level

IIa

*Pending approval; BID = twice daily; INR = international normalized ratio; NOAC = novel oral anticoagulant;
VKA = vitamin K antagonist; Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

27

NOAC-specific recommendations (2)

Recommendation

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 3049 mL/min)

IIa

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 3049 mL/min)

IIa

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

Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

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 23 times per year

IIa

NOACs (dabigatran, rivaroxaban, and apixaban) are not recommended

in patients with severe renal impairment (CrCl <30 mL/min)

III

CrCl = creatinine clearance; NOAC = novel oral anticoagulant

Camm AJ et al. Eur Heart J doi:10.1093/eurheartj/ehs253

Conclusion
Benefits of stroke prevention with aspirin is weak and
potentially dangerous, because the risk of major bleeding
(and ICH) with aspirin did not differ significantly with OAC,
especially in the elderly.
The use of antiplatelet therapy as a combination therapy of
aspirin-clopidogrel or aspirin monotherapy (less effective for
those who can not tolerate aspirin clopidogrel combination
therapy) for the prevention of stroke in AF should be limited
to a few patients who reject all forms of OAC.
Emphasises use of CHA2DS2-VASc score to identify truly low
risk patients who do not need antithrombotic therapy

Conclusion...contd
HAS-BLED score allows doctors to make judgments about the risk of
bleeding, and is important to make them think about the bleeding
risk factors that can be corrected. In patients with HAS-BLED score
3, prudence and recommended periodic reports, as well as efforts
to improve risk factors for bleeding are potentially reversible. A
high-HAS-BLED score per se should not be used to exclude patients
from OAC therapy

NOACs broadly preferable to VKA in the vast majority of patients

with nonvalvular AF
There is not enough evidence to recommend one over the other
NOAC, although some patient characteristics, medication
adherence, tolerability, and cost may be an important consideration
in drug selection.