Kháng tiểu cầu kép cho bệnh nhân sau HC vành cấp có bệnh động mạch ngoại biên (Cập nhật NC Pegasus)

PGS. TS Trương Quang Bình, FSCAI 
ĐHYD TPHCM 
Kháng tiểu cầu kép cho BN sau 
HC VÀNH CẤP 
có BỆNH ĐM NGỌAI BIÊN 
(cập nhật NC PEGASUS) 
Các khuyến cáo về thời gian dùng thuốc 
ức chế P2Y12 sau hội chứng mạch vành cấp 
Society Management Recommended Duration 
Medical 
Ideally up to 12 months 
PCI (DES) 
At least 12 months 
All 
12 months 
“Data suggest  SES or PES  may benefit from 
prolonged DAPT beyond 1 year.” 
“ data suggest that DAPT for 6 mos might be 
sufficient because late and very late ST correlate 
poorly with d/c of DAPT.” 
Medical 12 months 
PCI 12 months 
(After 12 mos, recommend single antiplatelet 
therapy over continuation of DAPT) 
2014 ACCF/AHA UA/NSTEMI; 2013 ACCF/AHA STEMI; 2011 ESC NSTEACS; 2012 ESC STEMI; 
2014 CHEST Antithrombotic Guidelines 
ACCP 
2 
Mauri et al. NEJM 2014. 
DOI:10.1056/NEJMoa1409312. 
DAPT: Tiếp tục hoặc ngưng thienopyridine 
sau 12 tháng dùng/Stent ĐMV 
Mauri et al. NEJM 2014. DOI:10.1056/NEJMoa1409312. 
Chết, NMCT hoặc đột quị 
Tiếp tục thienopyridine vs. placebo 
ở bệnh nhân có hoặc không có HCVC 
1802 1791 1761 1737 1704 1676 1649 
1766 1749 1706 1676 1632 1592 1553 
Thienopyridine 
Placebo 
4008 3982 3893 3830 3772 3705 3660 Placebo 
C
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D
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M
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S
tr
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0% 
2% 
4% 
6% 
8% 
A. ACS Patients 
C
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c
id
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f 
D
e
a
th
, 
M
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o
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S
tr
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k
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4050 4020 3951 3900 3851 3786 3718 Thienopyridine 
12 15 18 21 24 27 30 
0% 
2% 
4% 
6% 
8% 
Months After Enrollment 
B. Non-ACS Patients 
HR 0.56 (0.42-0.76) 
p<0.001 
6.8% Placebo 
3.9% 
Thienopyridine 
5.3% 
Placebo 
4.4% 
Thienopyridine 
HR 0.83 (0.68-1.02) 
p=0.08 
All DES and BMS randomized patients 
Interaction 
P = 0.03 
12 15 18 21 24 27 30 
Months After Enrollment 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
BN ổn định có t/s NMCT 1-3 năm trước 
+  1 YTNC huyết khối xơ vữa* 
Ticagrelor 
90 mg x 2/ngày 
Placebo 
PHÂN NGẪU NHIÊN 
MÙ ĐÔI 
Tái khám theo dõi 
mỗi 4 tháng năm 1, sau đó mỗi 6 tháng 
 Điều trị nền chuẩn, bao gồm 
ASA 75 – 150 mg 
* Tuổi >65, ĐTĐ, NMCT lần 2, bệnh MV nhiều nhánh, hoặc 
bệnh thận mạn không g/đ cuối 
TNLS dựa vào số biến cố 
Ticagrelor 
60 mg x 2/ngày 
Thiết kế nghiên cứu 
 ACC 2015 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Phân ngẫu nhiên 21,162 bệnh nhân 
Ticagrelor 
90 mg bid 
(N=7050) 
Placebo 
(N=7067) 
Ticagrelor 
60 mg bid 
(N=7045) 
Theo dõi 
Ngưng thuốc hẳn sớm 12%/yr 11%/yr 8%/yr 
Rút lại lời đồng ý 0.7% 0.7% 0.7% 
Mất theo dõi 3 bệnh nhân 6 bệnh nhân 1 bệnh nhân 
Theo dõi trung vị 33 tháng 
Min 16 tháng, max 47 tháng 
ACC 2015 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Tháng kể từ khi phân nhóm ngẫu nhiên 
Ticagrelor 60 mg 
HR 0.84 (95% CI 0.74 – 0.95) 
P=0.004 
C
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N
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, 
N
M
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T
, 
h
o
ặ
c
 đ
ộ
t 
q
u
ị 
(%
) 
3 6 9 12 0 15 18 21 24 27 30 33 36 
Ticagrelor 90 mg 
HR 0.85 (95% CI 0.75 – 0.96) 
P=0.008 
Placebo (9.0%) 
Ticagrelor 90 (7.8%) 
Ticagrelor 60 (7.8%) 
Tiêu chí đánh gia ́ chính: chết do nguyên nhân tim 
mạch, NMCT hoặc đột quị 
6 
5 
4 
3 
10 
9 
8 
7 
2 
1 
0 
N = 21,162 
Theo dõi trung vị 33 tháng 
ACC 2015 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Chảy máu 
P<0.001 
P<0.001 
P=NS P=NS P=NS 
Ticag 60: HR 2.32 (1.68-3.21) 
Ticag 90: HR 2.69 (1.96-3.70) 
ACC 2015 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Tóm tắt 
• Thêm ticagrelor vào trên nền aspirin liều thấp 
ở bệnh nhân có tiền sử NMCT làm giảm nguy 
cơ chết do NN tim mạch, NMCT, đột quị. 
• Ticagrelor tăng nguy cơ chảy máu nặng theo 
TIMI nhưng không tăng chảy máu gây chết 
hoặc chảy máu nội sọ. 
=> Một số đối tượng hưởng lợi khi dùng DAPT 
kéo dài đến 3 năm 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
2016 - DAPT SCORE 
• Lợi ích/ nguy cơ ≥ 
2 điểm nên kéo dài 
DAPT trên 12 
tháng 
• Lợi ích/ nguy cơ < 
2 không nên kéo 
dài DAPT trên 12 
tháng 
Efficacy and Safety of Ticagrelor as Long-Term 
Secondary Prevention in Patients with Peripheral 
Artery Disease and Prior Myocardial Infarction 
Marc P. Bonaca, MD, MPH 
on behalf of the PEGASUS-TIMI 54 Executive & 
Steering Committees and Investigators 
Hypotheses 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Patients with PAD and prior MI: 
1. Would be at heightened risk for both MACE and 
 MALE relative to patients without PAD 
2. Would derive a particularly robust reduction in 
 MACE risk with ticagrelor vs. placebo 
3. Would derive benefit for MALE with ticagrelor 
 vs. placebo 
Methods 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
1. PAD was identified by sites at baseline as evidenced by one or 
more of the following characteristics: 
 Ankle brachial index (ABI) ≤ 0.90, Prior peripheral revascularization, Claudication 
2. CV death, MI, stroke, bleeding, and acute limb ischemia were 
prospectively collected and formally adjudicated. Peripheral 
revascularizations were site reported. 
3. Major adverse limb events (MALE) was defined as the 
composite of acute limb ischemia (ALI) or peripheral 
revascularization for limb ischemia 
4. Analyses comparing risk in the placebo group by baseline 
PAD were adjusted for baseline differences 
Baseline Characteristics by PAD 
No PAD 
N=20,017 
PAD 
N=1,143 
Age, median (IQR) 65 (59, 71) 66 (60, 73) 
Gender (female) 24 22 
History Hypertension 77 85 
Risk 
Factors 
History of Hypercholesterolemia 77 81 
Current Smoker 16 30 
History of COPD 7 68 
eGFR < 60 (MDRD) 23 31 
History of Diabetes 32 42 
History of CHF 19 30 
CV 
Disease 
History of Second Prior MI 16 26 
Multivessel Coronary Artery Disease 59 64 
Prior CABG 4 13 
ABI <=0.90 0 19 Limb 
Disease Peripheral Revascularization 0 34 
History of claudication 0 65 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School All p-values < 0.001 except gender (p=0.17) 
Background ASA >99%, statin>93%, beta blocker 83% no significant 
difference by baseline PAD 
0 
5% 
10% 
15% 
20% 
25% 
% 
0 90 180 270 360 450 630 810 990 108 
C
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a
th
, 
M
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S
tr
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(%
) 
PAD Patients 
N=404 
19.3% 
Patients without 
PAD 
N=6663 
8.4% 
Number at Risk 
PAD 
No PAD 
404 
6663 
384 
6508 
367 
6394 
P<0.001 
MACE in Patients* by PAD 
540 720 900 1080 
344 309 223 104 
6159 5567 4120 1924 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School *randomized to placebo Days from Randomization 
C
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M
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S
tr
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 (
%
) 
0% 
5% 
10% 
15% 
20% 
25% 
0 90 180 270 360 450 540 630 720 810 900 990 1080 
19.3% 
15.2% 
8.4% 
7.4% 
PAD 
HR 0.75 
95% (CI 0.55 – 1.01) 
ARR 4.1% 
NNT 25 
No PAD HR 
0.86 
95% (CI 0.77 – 
0.96) 
P-interaction 0.41 
Placebo 
Ticagrelor 
(pooled doses) 
ARR 1.0% 
NNT 100 
MACE with Ticagrelor by PAD at Baseline 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School Days from Randomization 
A
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Is
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m
ia
(%
) 
0.2% 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School Days from Randomization 
1.0% 
0.8% 
0.71% 
0.6% 
0.46% 
0.4% 
HR 0.65 
95% CI (0.44 – 0.95) 
P=0.026 
0.0% 
Number at Risk 
Placebo 
Ticagrelor 14095 
13929 13789 13425 12186 9154 
0 180 360 540 720 900 1080 
7067 6988 6912 6701 6077 4518 2123 
4296 
Major Adverse Limb Events with Ticagrelor 
Placebo 
Ticagrelor 
(pooled doses) 
Summary 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
Patients with prior MI and concomitant PAD 
– Are at heightened risk of ischemic vascular 
complications and mortality even after adjusting for 
comorbidities 
– Ticagrelor added to aspirin reduced MACE with a robust 
ARR (>4%) & NNT (25) at 3 years 
– Ticagrelor added to aspirin reduced limb ischemic events 
Conclusions 
An Academic Research Organization of 
Brigham and Women’s Hospital and Harvard Medical School 
• Patients with PAD and prior MI are at heightened 
risk of ischemic cardiovascular and limb events 
and derive a robust risk reduction from long-
term secondary prevention with ticagrelor 
• The ongoing EUCLID trial will evaluate the 
efficacy of ticagrelor vs. clopidogrel 
monotherapy in patients with PAD for major 
adverse cardiovascular and limb events 
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