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.0
0 1 2 3 4 5 6
Time from randomization (years)
3.34%/yr
2.76%/yr
C
u
m
u
la
ti
v
e
 r
is
k
Major bleeding
RE-LY® RELY-ABLE®
0.25
0.20
0.15
0.05
0.10
0.0
0 1 2 3 4 5 6
Time from randomization (years)
1.54 %/yr
1.25 %/yr
Stroke/SE
RE-LY® RELY-ABLE®
Dabigatran 150 mg BID
26
Kết quả RELY-ABLE®
D150, dabigatran 150 mg BID; D110, dabigatran 110 mg BID
1. Ezekowitz M et al. Europace 2016
Favours D110Favours D150
D150
ICH
D110
D150
Major bleeding
D110
0.5 1 1.5 2.00
RR
D150
Stroke/SE
D110
P=0.11
P=0.00081
P=0.01
45 (0.23)
529 (2.76)
62 (0.32)
246 (3.34)
296 (1.54)
243 (1.25)
n (%/year)
27
RELY-ABLE® kết luận: 
• dabigatran 150 mg BID hiệu quả hơn
• dabigatran 110 mg BID ít chảy máu nặng hơn
• tỷ lệ XH nội sọ thấp cho cả 2 liều
Kết quả RELY-ABLE® thống nhất với RE-LY® cho cả
2 liều dabigatran qua hơn 6.7 năm theo dõi
*Category includes ‘or type uncertain’
1. Connolly SJ et al. N Engl J Med 2009; 2. Connolly SJ et al. N Engl J Med 2010; 3. Connolly SJ et al. N Engl J Med 2014; 4. Ezekowitz 
M et al. Europace 2016
RE-LY®1–3
D150 BID
D110 BID
RELY-ABLE®4
D150 BID
D110 BID
E
V
E
N
T
 R
A
T
E
 (
%
 P
E
R
 Y
E
A
R
)
5
4
3
2
1
0
0
1
2
3
4
5
STROKE
/SE
ICH
MAJOR
BLEEDING
ISCHAEMIC 
STROKE*
MORTALITY
GI
BLEEDING
2.76
3.34
1.26
1.50
0.230.32
1.54
1.25 1.29
1.03
3.553.43
2.92
3.40
1.15
1.56
0.230.32
1.54
1.12
1.34
0.93
3.75
3.64
E
V
E
N
T
 R
A
T
E
 (
%
 P
E
R
 Y
E
A
R
)
28
29
Eur Heart J (2016) 37 (38): 2893-2962-https://doi.org/10.1093/eurheartj/ehw210
Stroke prevention in patients with atrial fibrillation
Recommendations Class Level
Oral anticoagulation therapy to prevent thromboembolism is recommended for all male 
AF patients with a CHA2DS2-VASc score of 2 or more.
I A
Oral anticoagulation therapy to prevent thromboembolism is recommended in all female 
AF patients with a CHA2DS2-VASc score of 3 or more.
I A
Oral anticoagulation therapy to prevent thromboembolism should be considered in male 
AF patients with a CHA2DS2-VASc score of 1, considering individual characteristics and 
patient preferences.
IIa B
Oral anticoagulation therapy to prevent thromboembolism should be considered in 
female AF patients with a CHA2DS2-VASc score of 2, considering individual characteristics 
and patient preferences.
IIa B
Vitamin K antagonist therapy (INR 2.0–3.0 or higher) is recommended for stroke 
prevention in AF patients with moderate-to-severe mitral stenosis or mechanical heart 
valves.
I B
When oral anticoagulation is initiated in a patient with AF who is eligible for a NOAC 
(apixaban, dabigatran, edoxaban, or rivaroxaban), a NOAC is recommended in preference 
to a Vitamin K antagonist.
I A
Eur Heart J (2016) 37 (38): 2893-2962-https://doi.org/10.1093/eurheartj/ehw210
ESC 2016 Guidelines:
When OAC Is Initiated, NOACs Are Recommended
Eur Heart J (2016) 37 (38): 2893-2962-https://doi.org/10.1093/eurheartj/ehw210
Recommendations Class Level
When patients are treated with a vitamin K antagonist, time in therapeutic range (TTR) 
should be kept as high as possible and closely monitored.
I A
AF patients already on treatment with a vitamin K antagonist may be considered for NOAC 
treatment if TTR is not well controlled despite good adherence, or if patient preference 
without contra-indications to NOAC (e.g. prosthetic valve).
IIb A
Combinations of oral anticoagulants and platelet inhibitors increase bleeding risk and 
should be avoided in AF patients without another indication for platelet inhibition.
III
(harm)
B
In male or female AF patients without additional stroke risk factors, anticoagulant or 
antiplatelet therapy is not recommended for stroke prevention.
III
(harm)
B
Antiplatelet monotherapy is not recommended for stroke prevention in AF patients, 
regardless of stroke risk.
III
(harm)
A
NOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) are not recommended in 
patients with mechanical heart valves (Level of evidence B) or moderate-to-severe mitral 
stenosis (Level of evidence C).
III
(harm)
B C
Stroke prevention in patients with atrial fibrillation
Eur Heart J (2016) 37 (38): 2893-2962-https://doi.org/10.1093/eurheartj/ehw210
Chương trình nghiên cứu - phát triển
của Dabigatran năm 2017
2017 has seen the release of new trial data for dabigatran 
and idarucizumab
35
ACC 
2017
ESC 
2017
ISTH
2017 
ACC, American College of Cardiology; ESC, European Society of Cardiology; ISTH, International Society on Thrombosis and 
Haemostasis. Calkins et al. N Engl J Med 2017; Pollack et al. N Engl J Med 2017; Cannon et al. N Engl J Med 2017. See slide notes for 
details of congress presentations
Dabigatran ở BN điều trị rung nhĩ bằng sóng RF
36
Expert consensus provides the highest recommendation (1A) that the ablation procedure is 
performed without interruption of dabigatran 
ARR 5.3% (95% CI: 8.4–2.2);
RRR 77%; P<0.001
1.6
6.9
0
2
4
6
8
10
Dabigatran
150 mg BID
(n=317)
Warfarin
(n=318)
P
a
ti
e
n
ts
 w
it
h
 I
S
T
H
 m
a
jo
r 
b
le
e
d
in
g
 (
%
)Objective:
Investigate safety and efficacy of dabigatran 
150 mg BID as an alternative to warfarin (INR 2.0–3.0) 
in patients undergoing AF ablation (N=678) 
Results: 
Lower risk of major bleeding during and after ablation 
with uninterrupted dabigatran vs warfarin
= 6782017
Calkins et al. N Engl J Med 2017; Calkins et al. Heart Rhythm 2017 
Idarucizumab là đối kháng đặc hiệu của dabigatran
37
Results:
Idarucizumab provided immediate, complete, 
and sustained reversal of dabigatran 
anticoagulation
Objective:
To demonstrate the extent of reversal of the 
anticoagulant effect of dabigatran in patients 
who have uncontrolled/life-threatening 
bleeding, or those requiring emergency 
surgery/other invasive procedures for which 
normal haemostasis is desirable
Time post-idarucizumab
Group A: uncontrolled bleeding 
(N=293)
d
T
T
 (
s
)
110
70
60
50
40
30
100
90
80
1h 2h 4h 12h 24h10–30
min
0
Idarucizumab 
2×2.5 g
120
Group B: emergency surgery or 
procedure (N=195)
30
1h 2h 4h 12h 24h10–30
min
0
Time post-idarucizumab
Idarucizumab 
2×2.5 g
110
70
60
50
40
100
90
80
120
10th/90th percentiles 5th/95th percentilesMedian and 25th/75th percentiles Assay upper limit of normal
Dabigatran is the only NOAC that has an option to immediately reverse the anticoagulant activity 
in emergency situations (urgent surgery or life-threatening bleeding)
2017 = 503
Pollack et al. N Engl J Med 2017; Praxbind SPC 2017
Dabigatran ở BN rung nhĩ sau PCI
38
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
0
Dabigatran 150 mg 
dual therapy
Warfarin
triple therapy
HR: 0.72 (95% CI: 0.58–0.88)
Non-inferiority P<0.001
P=0.002
ISTH major bleeding or CRNMBE with dabigatran dual therapy
Dual therapy with dabigatran offers clinicians two additional options for the treatment of 
patients with varying risks of thromboembolic events and bleeding
0
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
Dabigatran 110 mg 
dual therapy
HR: 0.52 (95% CI: 0.42–0.63)
Non-inferiority P<0.001
P<0.001
Warfarin
triple therapy
Results: dual therapy with dabigatran 
significantly reduced the risk of 
bleeding vs warfarin triple therapy, 
with non-inferiority for overall 
thromboembolic events
Objective: investigate safety and 
efficacy of dabigatran plus single 
antiplatelet as an alternative to 
warfarin (INR 2.0–3.0) plus dual 
antiplatelets following PCI in patients 
with AF
P
ro
b
ab
ili
ty
 o
f 
e
ve
n
t 
(%
)
2017 = 2725
CRNMBE, clinically relevant non-major bleeding event; PCI, percutaneous coronary intervention
Cannon et al. N Engl J Med 2017
Eur Heart J. Published online March 19, 2018. doi:10.1093/eurheartj/ehy136
Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. 
Khi chuyển từ Warfarin sang NOAC, chỉ bắt đầu dùng NOAC khi INR <2.5. Khi
chuyển từ NOAC sang Warfarin, dùng cả Warfarin và NOAC cho đến khi INR
≥2 thì ngừng NOAC. Làm lại INR 1-3 ngày sau khi ngừng NOAC để chắc chắn
INR vẫn trong khoảng điều trị.
Khi nào bắt đầu dùng lại NOAC sau thủ thuật, thăm dò chảy máu?
Eur Heart J. Published online March 19, 2018. doi:10.1093/eurheartj/ehy136
Procedural and/or anatomical factors may drive longer triple therapy regimens. Beyond those
patients at very high ischaemic risk, early dual therapy may well become the default strategy
for most patients based on PIONEER AF-PCI and RE-DUAL PCI. In a small subset of patients
with a low stroke risk (CHA2DS2- VASc of 0–1 in males or 1–2 in females, i.e. only ACS) and
elevated bleeding risk, one could opt to treat with DAPT only, without anticoagulants, from
the onset
Eur Heart J. Published online 
March 19, 2018. 
doi:10.1093/eurheartj/ehy136
Eur Heart J. Published online March 19, 2018. doi:10.1093/eurheartj/ehy136
Xử trí biến chứng chảy máu ở BN đang dùng NOAC
Sử dụng, sử dụng lại NOAC ở BN nhồi máu não mới
Eur Heart J. Published online March 19, 2018. doi:10.1093/eurheartj/ehy136
KẾT LUẬN
Các nghiên cứu RCTs cho thấy hiệu quả trên phòng ngừa cả 2 
loại đột quỵ (xuất huyết và nhồi máu) của Dabigatran 150 mg, 
cũng như tính an toàn được thiết lập, đặc biệt trên dân số
châu Á
1
Chương trình nghiên cứu phát triển thuốc của Dabigatran tiếp 
tục mở rộng trên các bệnh nhân can thiệp cắt đốt rung nhĩ và 
can thiệp mạch vành, khẳng định tính an toàn của Dabigatran 
ở các đối tượng trên.
2
EHRA 2018 cập nhật hướng dẫn sử dụng kháng đông và chất
hoá giải đặc hiệu của Dabigatran (Idarucizumab) trong các tình
huống lâm sàng cụ thể nhằm tối ưu điều trị cho bệnh nhân.3
45
Eur Heart J. Published online March 19, 2018. doi:10.1093/eurheartj/ehy136