Tối ưu điều trị thuyên tắc phổi cấp trên bệnh nhân có tiền sử nhồi máu cơ tim - Nguyễn Ngô Thanh Phương

 Tối ưu điều trị thuyên tắc phổi cấp 
trên bệnh nhân có tiền sử 
nhồi máu cơ tim 
Bs. Nguyễn Ngô Thanh Phương 
BS. Đinh Đức Huy 
Bv Tim Tâm Đức 
Trường hợp lâm sàng 
• Bệnh nhân C. J, 50 tuổi 
• BMI 28 (CC 183cm, CN 96kg) 
• Hút thuốc lá(+) 
• Rối loạn mỡ máu (+) 
• THA (-), ĐTĐ (-) 
• Tiền căn NMCT ST chênh lên (2011)  can thiệp 
1 stent không phủ thuốc vào đoạn đầu LAD 
• Điều trị : Aspirin, Bisoprolol, Losartan, 
Rosuvastatin 
• BN không triệu chứng 
• 1 tháng trước, bệnh nhân bay từ HCM-London 
• Khó thở khi gắng sức ngày càng tăng 
• Đau chân bên phải 
• Nhập viện vì khó thở 
• Tỉnh táo, không dấu thần kinh khu trú, không sốt 
• TST 88 bpm HA 135/80 mmHg 
• TS thở 16 bpm SpO2 96% (room air) 
• Tim đều, không âm thổi 
• Phổi trong 
• Chân bên phải hơi lớn hơn chân bên trái 
Trường hợp lâm sàng 
• BC 9.7k/uL, HGB 15 g/dL, TC 200K/uL 
• Creatinin 101 mmol/L, eGFR:78ml/ph/1.73m2 
• Hs-CRP 70mg/L 
• AST 26 U/L ALT 28 U/L 
• Cholesterol 2.1 HDL-C 0.5 
 LDL-C 1.5 TG: 1.2 mmol/L 
• NT proBNP 1692pg/ml 
• Hs-TnT 21-22 pg/ml 
• D-Dimer 5990 ng/mL 
Xét nghiệm 
ECG 
Sinus rythm, 85 bpm, normal QRS axis and PR interval 
Cận lâm sàng 
Siêu âm tim 
• EF 62%, không RLVĐ vùng 
• Không bệnh lý van tim 
• Không tăng áp phổi (PAPs 
=20mmHg) 
• Không huyết khối 
• Lớn thất phải, TAPSE 19 
Siêu âm mạch máu 
• Tắc hoàn toàn tĩnh mạch 
đùi nông bên phải 
• Huyết khối lan tỏa đến 
tĩnh mạch khoeo bên phải 
CTR: 0.55 
Tuần hoàn phổi bên phải giảm 
 Thuyên tắc phổi/ Nhồi máu cơ tim đã đặt 1 stent 
 Xác định bằng MSCT phổi 
Chẩn đoán 
Xử trí 
Ngày 1-2: 
 Enoxaparin 0.9ml TDD /12 giờ 
 Acenocoumarol 1mg / ngày 
 ASA 81mg /ngày 
 Bisoprolol 2.5mg /ngày 
 Losartan 25mg /ngày 
 Rosuvastatin 10mg /ngày 
Ngày 3: Bệnh nhân từ chối kiểm tra INR hằng 
ngày 
VTE treatment with VKAs 
• VKAs = standard treatment for VTE (PE & DVT) 
• Highly prevent recurrent VTE (RRR 85% vs placebo) 
• Recurrence risk of 3% with patient on treatment 
• Limitations of VKA treatment 
 need frequent INR monitoring 
 major bleeding of 2.1% during the first 6 months of treatment 
 case-fatality rate 11% 
 intracranial bleeding 8.7% of major bleeds with mortality risk of 46% 
 most major bleeds occur during the first weeks of VKA treatment 
N Engl J Med 2012;366:1287-97 
EINSTEIN PE: study design 
Randomized, open-label, event-driven, non-inferiority study 
• Up to 48 hours’ heparins/fondaparinux treatment permitted before study entry 
• 88 primary efficacy outcomes needed 
• Non-inferiority margin: 2.0 
Predefined treatment period of 3, 6, or 12 months 
15 mg bid 
Rivaroxaban 
Day 1 Day 21 
Enoxaparin bid for at least 5 days, 
plus VKA INR 2.5 (range 2.0–3.0) 
20 mg od 
N=4833 
Rivaroxaban 
R 
Objectively 
confirmed PE ± 
DVT 
30-day post-
study 
treatment 
period 
 Primary efficacy outcome: first recurrent VTE 
 Principal safety outcome: first major or nonmajor clinically relevant bleeding 
Patient flow 
*As treated 
Withdrawal of consent 
Lost to follow-up 
Safety population* 
ITT population 
Randomized 
(N=4833) 
Per-protocol population 
66 
8 
2420 
2419 
2412 
2224 
Rivaroxaban 
118 
10 
Enoxaparin/VKA 
2413 
2413 
2405 
2238 
EINSTEIN PE: primary efficacy 
outcome analysis 
Rivaroxaban 
(N=2419) 
Enoxaparin/VKA 
(N=2413) 
n (%) n (%) 
First symptomatic recurrent VTE 50 (2.1) 44 (1.8) 
Recurrent DVT 18 (0.7) 17 (0.7) 
Recurrent DVT + PE 0 2 (<0.1) 
Non-fatal PE 22 (0.9) 19 (0.8) 
Fatal PE/unexplained death where 
PE cannot be ruled out 
10 (0.4) 6 (0.2) 
Rivaroxaban 
superior 
Rivaroxaban 
non-inferior 
Rivaroxaban 
inferior 
P=0.0026 for non-inferiority 
(one-sided) 
p=0.57 for superiority 
(two-sided) 
1.00 0 2.00 
0.75 1.12 1.68* 
*Potential relative risk increase <68.4%; absolute risk difference 0.24% (–0.5 to 1.02) 
HR 
EINSTEIN PE: principal safety outcome – 
major or non-major clinically relevant bleeding 
Rivaroxaban 
n/N (%) 
Enoxaparin/VKA 
n/N (%) 
HR (95% CI) 
p-value 
249/2412 
(10.3) 
274/2405 
(11.4) 
0.90 (0.76–1.07) 
p=0.23 
Safety population 
0 30 60 90 120 150 180 210 240 270 300 330 360 
15 
14 
10 
13 
12 
11 
9 
8 
7 
6 
5 
4 
3 
2 
1 
0 
Number of patients at risk 
Rivaroxaban 2412 2183 2133 2024 1953 1913 1211 696 671 632 600 588 313 
Enoxaparin/VKA 2405 2184 2115 1990 1923 1887 1092 687 660 620 589 574 251 
Time to event (days) 
Rivaroxaban 
N=2412 
Enoxaparin/VKA 
N=2405 
C
u
m
u
la
ti
v
e
 e
v
e
n
t 
ra
te
 (
%
) 
Safety population 
3.0 
2.5 
2.0 
1.5 
1.0 
0.0 
0.5 
0 30 60 90 120 150 180 210 240 270 300 330 360 
C
u
m
u
la
ti
v
e
 e
v
e
n
t 
ra
te
 (
%
) 
Time to event (days) 
Rivaroxaban 
N=2412 
Enoxaparin/VKA 
N=2405 
Number of patients at risk 
Rivaroxaban 2412 2281 2248 2156 2091 2063 1317 761 735 700 669 659 350 
Enoxaparin/VKA 2405 2270 2224 2116 2063 2036 1176 746 719 680 658 642 278 
EINSTEIN PE: major bleeding 
Rivaroxaban 
n/N (%) 
Enoxaparin/VKA 
n/N (%) 
HR (95% CI) 
p-value 
26/2412 
(1.1) 
52/2405 
(2.2) 
0.49 (0.31–0.79) 
p=0.0032 
EINSTEIN PE: conclusions 
In patients with acute symptomatic PE with or without DVT, 
rivaroxaban showed: 
Non-inferiority to LMWH/VKA for efficacy 
 HR=1.12 (0.75–1.69); pnon-inferiority =0.0026 
 for non-inferiority margin of 2.0 
Similar findings for principal safety outcome 
HR=0.90 (0.76–1.07); p=0.23 
Superiority for major bleeding 
HR=0.49 (0.31–0.79) p=0.0032 
Consistent efficacy and safety results irrespective of age, 
body weight, gender, kidney function and cancer 
No evidence for liver toxicity 
Clinical trials of NOACs for PE acute phase 
Systemic review and meta-analysis 
Introduction: 
Meta-analysis to determine the efficacy and safety of NOACs as 
compared with those of VKAs in patients with acute VTE 
Methods: 
MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews 
and the Clinical Trials Registry up to October 2013. Eligible studies 
included phase 3 trials comparing NOACs with VKAs in patients with 
acute VTE. RRs, absolute risk differences and NNTs to prevent one 
event were calculated for recurrent VTE, fatal PE, overall mortality, 
major bleeding, and other bleeding complications, with random-
effects models. 
Study outcomes & Definitions 
1. Efficacy outcomes 
 Recurrent VTE, fatal PE, and overall mortality 
2. Safety outcomes 
 Major bleeding, non-fatal major bleeding at a critical site, 
 clinically relevant non-major bleeding, non-fatal intracranial 
 bleeding, major gastrointestinal bleeding, and fatal bleeding 
 during anticoagulant treatment 
3. Definition of major bleeding 
 Overt and associated with a decrease in the Hb level of 
 ≥2g/dL, requiring transfusion of at least 2 units of blood, 
 occurring in a critical site (intracranial, intraspinal, intraocular, 
 pericardial, intra-articular intramuscular with compartment 
 syndrome, retroperitoneal), or contributing to death 
Study selection 
Study characteristics 
Main findings 
1. Five studies were included, 4 NOACs (rivaroxaban, dabigatran, 
apixaban, edoxaban) in 24 455 patients with acute VTE 
2. RR for 
 recurrent VTE 0.88 (95% CI 0.74–1.05) 
 fatal PE 1.02 (95% CI 0.39–5.96) 
 overall mortality 0.97 (95% CI 0.83–1.14) 
 major bleeding 0.60 (95% CI 0.41–0.88) 
 fatal bleeding 0.36 (95% CI 0.15–0.87) 
3. NNT to prevent 
 one major bleed 149 
 one fatal bleed 1111 
4. No significant differences between individual NOACs and 
rivaroxaban (Fixed-effect network analysis ) 
Efficacy outcomes 
Recurrent VTE 241/12 151 patients (2.0%) vs 273 /12 153 patients (2.2%) 
Fatal PE 9/12 151 patients (0.07%) vs 9/12 153 patients (0.07%) 
Mortality 290 /12 197 patients (2.4%) vs 298 /12 193 patients (2.4%) 
Safety outcomes 
1. NOACs show comparable efficacy to VKAs in 
patients with acute VTE 
2. Greater practical simplicity 
3. More favorable bleeding profile 
4. Absolute benefit was limited with high NNT 
Meta analysis conclusions 
2014 ESC Guidelines 
Recommendations for 
Acute phase treatment 
Class I B for NOACs 
as an alternative to the 
combination of parental 
anticoagulation with a VKA 
www.escardio.org/guidelines 
1. Rivaroxaban 15mg 2 lần/ngày x 3 tuần 
2. Duy trì các thuốc khác: aspirin, losartan, 
bisoprolol, rosuvastatin 
3. Rivaroxaban 20mg /ngày đến 6 tháng 
4. Ngưng kháng đông thế hệ mới 08/ 2015, 
không biến chứng chảy máu 
5. Tiếp tục điều trị nội khoa mạch vành sau can 
thiệp 
6. Sử dụng vớ áp lực 
Điều trị của bệnh nhân 
Thank you for your attention!