VAI TRÒ THUỐC CHỐNG ĐÔNG ĐƯỜNG UỐNG MỚI TRONG PHÒNG NGỪA ĐỘT QUỴ Ở BỆNH NHÂN RUNG NHĨ KHÔNG DO BỆNH VAN TIM

Ts.Bs. Đinh Hiếu Nhân
Đại Học Y Dược TpHCM

VAI TRÒ THUỐC CHỐNG
ĐƠNG ĐƯỜNG UỐNG
MỚI TRONG PHỊNG
NGỪA ĐỘT QUỴ Ở BỆNH
NHÂN RUNG NHĨ KHÔNG
DO BỆNH VAN TIM


I. TỔNG QUAN


Definitions of AF: A Simplified Scheme
Term

Definition

Paroxysmal AF




AF that terminates spontaneously or with intervention within 7 d of onset.
Episodes may recur with variable frequency.

Persistent AF



Continuous AF that is sustained >7 d.

Long-standing
persistent AF



Continuous AF >12 mo in duration.

Permanent AF



The term “permanent AF” is used when the patient and clinician make a
joint decision to stop further attempts to restore and/or maintain sinus
rhythm.
Acceptance of AF represents a therapeutic attitude on the part of the
patient and clinician rather than an inherent pathophysiological attribute of
AF.
Acceptance of AF may change as symptoms, efficacy of therapeutic
interventions, and patient and clinician preferences evolve.




Nonvalvular AF



AF indicates atrial fibrillation.

AF in the absence of rheumatic mitral stenosis, a mechanical or
bioprosthetic heart valve, or mitral valve repair.


Atrial fibrillation



AF is the most common heart rhythm disturbance1



It is estimated that 1 in 4 individuals aged 40 years will
develop AF1



In 2007, 6.3 million people in the US, Japan, Germany,
Italy, Spain, France, and UK were living with diagnosed
AF2



Owing to the aging population, this number is expected to
double within 30 years3
1. Lloyd-Jones DM et al. Circulation 2004;110:1042-1046.
2. Decision Resources. Atrial Fibrillation Report. Dec 2008.
3. Go AS et al. JAMA. 2001;285:2370-2375.

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg





Rationale for Stroke Prevention in AF







AF is associated with a 25% life-time risk of stroke1
Cardio-embolic stroke has a 30-day mortality
of 25% and a 1 year mortality of almost 50%2
Cardio-embolic strokes are more severe and more often
disabling than strokes of other etiology
Once a stroke has happened the risk for subsequent
cardio-embolic stroke is increased 2-3fold
AF-related stroke has a 1-year mortality of ~50%3
1. Wolf PA et al. Stroke. 1991;22:983-988. 2. Lin H-J et al. Stroke. 1996; 27:1760-1764.
3. Marini C et al. Stroke. 2005;36:1115-1119..

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg


Anticoagulation in AF: Stroke Risk Reduction



In the past, the most widely used medications for stroke
prevention in patients with AF were vitamin K-antagonists
(VKAs) and aspirin



VKAs are very effective in preventing stroke among
AF- patients
• Almost 70% relative risk reduction vs placebo

Kirchhof P et al. Working Group Report, 2009.

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg


Stroke Risk Reduction in AF (Warfarin vs placebo)
AFASAK: Peterson et al

811

Lancet 1989;1:175

BAATAF: Investigators

922

NEJM 1990;323;1505

CAFA: Connolly et al,

478

JACC 1991;18:349

SPAF: Investigators

508

Stroke 1990;21:538

SPINAF: Ezekowitz et al

972

NEJM 1992;327:1406

3691

COMBINED
100%

50%

Warfarin better

0%

–50%

–100%

Warfarin worse

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg

Arch Intern Med 1994;154:1449-1457


CHA2DS2-VASc score and stroke risk in AF
Points

CHA2DS2VASc

1-year
stroke rate

Previous stroke
TIA or systemic
embolism

2

9

23.64%

8

22.38%

Age ≥75 years

2

7

21.50%

Congestive heart
failure*

1

6

19.74%

5

15.26%

Hypertension

1

4

9.27%

Diabetes mellitus

1

3

5.92%

Age 65–74 years

1

2

3.71%

Female gender

1

1

2.01%

Vascular disease

1

0

0.78%

Item

Add points
together

*Or moderate-to-severe left ventricular systolic dysfunction (LVEF ≤40%)

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg

Olesen JB, et al. BMJ. 2011;342:d124;
Camm AJ, et al. Eur Heart J. 2010;31:2369-2429.


II. ĐIỀU TRỊ


TIẾP CẬN ĐIỀU TRỊ RUNG NHĨ



Overview of AF Management
AF Detected

Management of
Arrhythmia

Assessment of

Thromboembolic Risk
(CHA2DS2-VASc score )

ASA
OAC

Rate
Control

No antithrombotic therapy may be appropriate in selected
young patients with no stroke risk factors

Rhythm
Control


Coagulation Cascade
Intrinsic Pathway
(Contact Activation)
XII

Extrinsic Pathway
(Tissue Factor)
XI
Tissue
Factor

IX

VIII

VKAs

VII

X

Factor Xa Inhibitors (-AT)
Apixaban and Rivaroxaban

V

II

Fibrinogen

Direct Thrombin Inhibitors
Dabigatran

Fibrin Clot

Adapted with
permission from
Nutescu et al.


Anticoagulation in AF: Stroke
Risk Reduction
• In the past, the most widely used medications
for stroke prevention in patients with AF were

vitamin K-antagonists (VKAs) and aspirin

• VKAs are very effective in preventing stroke
among AF- patients
– Almost 70% relative risk reduction vs placebo
Kirchhof P et al. Working Group Report, 2009.


Underutilization of OAKs in Atrial
Fibrillation

Go et al Ann Intern Med 1999
Samsa et al Arch Intern Med 2000
Gage et al Stroke 2000

Waldo et al J Am Coll Cardiol 2005
Nieuwlaat et al Eur Heart J 2006
Hylek et al Stroke 2006

Birman-Deych et al Stroke 2006
Friberg et al Eur Heart J 2006

Monte et al Eur Heart J 2006
Boulanger et al Int J Clin Pract 2006


And When AC Was Given, The TTR Was
Far From Good
“Time in therapeutic range” (TTR) in
daily

Time in therapeutic range (%)

100
80

63
60

51

47
40

56
49

52

55

51
42

36

20
0

Samsa

20002
n = 61

Samsa McCormick Matchar
20002
20013
20034*
n = 125
n = 174 n = 363

Matchar
20034*
n = 317

Matchar
20034*
n = 317

Go
Shen
5
2003
20076
n = 7445 n = 11,016

Nichol
20087*
n = 756

Subtotal†

The 50 /50 Rule
• About 50% of the patients who need VKAOACs don´t get it

•

Of those who get VKA-OACs, 50% are outside the
therapeutic range

75% BN ĐIỀU TRỊ KHÔNG HIỆU QUẢ
HAY KHÔNG ĐIỀU TRỊ.


VKAs have a narrow therapeutic
window
Adjusted odds ratios for ischaemic stroke and intracranial
bleeding in relation to intensity of anticoagulation

Odds ratio for event

20

15
Ischaemic
stroke

10

Intracranial

bleeding

Target
INR

5

1
1.0

2.0
3.0
4.0
5.0
6.0
International normalized ratio

Adapted from Wann et al. Circulation 2011;123;e269-e367

7.0

8.0


Factor Xa Inhibitors And Direct Thrombin
Inhibitors For Stroke Prevention in AF

DTI, direct thrombin inhibitor

Metaanalysis





This meta-analysis is the first to include data for all four
new oral anticoagulants studied in the pivotal phase 3
clinical trials for stroke prevention or systemic embolic
events in patients with atrial fibrillation.
New oral anticoagulants had a favourable risk–benefit
profile, with significant reductions in stroke, intracranial
haemorrhage, and mortality, and with similar major
bleeding as for warfarin, but increased gastrointestinal
bleeding.
Ruff et al Lancet 2014

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg


Metaanalysis



Primary endpoint

Ruff et al Lancet 2014

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg

Metaanalysis

Ruff et al Lancet 2014

Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg