Statin trong hội chứng vành cấp

ng Huan,PhD,FACC,FSCAI 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
 10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
Neutrophil 
 10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
 10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
Quá trình viêm 
 Nứt, vỡ mãng xơ vữa  Tạo huyết khối 
 Sẹo hóa cơ tim 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
10/12/2014 
 Thermography Catheter 
 Stefanadis and al, Circulation 1999,99:1965-1971 
DO QUANG HUAN, MD, PhD, FACC, FSCAI 
Phản ứng viêm đóng vai trò quyết định trong HCVC 
Vai trò của Statin trong điều trị BN HCVC? 
10/12/2014 TS.BS DO QUANG HUAN 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
ARMYDA-CAMs RESULTS 
Atorvastatin Placebo 
0 
20 
40 
60 
80 
100 
ICAM-1 E-selectin VCAM-1 
P=0.0001 
P=0.0001 
P=0.20 
30 
59 
78 
42 
(76 pts) 
( 38pts) ( 38pts) 
10/12/2014 
 Tác dụng kháng kết tập tiểu cầu 
0
10
20
30
40
50
Placebo Statin
Before
After
P<0.01 
43+15 
45+12 
46+15 
32+6 
PLT CD40L expression (AU) 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
 Tác dụng kháng đông máu 
0
1
2
3
Placebo Statin
Before
After
Sanguigni V, et al. Circulation 2005 
2+1 2+1 2+1 
1.4+0.4 
P<0.05 
Prothrombin fragment F1+2 (nM) 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
Dãn mao mạch vành 
0
1
2
3
4
Placebo Statin
Before
After
Coronary flow velocity reserve 
(hyperemic/basal peak diastolic velocity) 
P<0.01 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
  Statin làm giảm quá trình viêm trong HCVC, kháng kết tập 
tiểu cầu, kháng đông, dãn mao mạch vành, và làm giảm tổn 
thương cơ tim sau tái tưới máu. 
 Trên thực tế lâm sàng Statin có làm giảm tỷ lệ tử vong, tỷ lệ 
tái NMCT, tái thông MV không? 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
The beneficial effect of high loading dose of rosuvastatin 
before percutaneous coronary intervention in patients 
with acute coronary syndrome 
 Kyeong Ho Yun, Myung Ho Jeong, Seok Kyu Oh, Sang Jae Rhee, Eun Mi 
Park, Eun Mi Lee, Nam Jin Yoo 
Department of Cardiovascular Medicine, Wonkwang University Hospital, Iksan, 
Republic of Korea 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients 
with acute coronary syndrome 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients 
with acute coronary syndrome 
hs-CRP 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients 
with acute coronary syndrome 
MACEs 30 days 
P=0,002 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI 
12 months follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients 
with acute coronary syndrome 
10/12/2014 TS.BS DO QUANG HUAN 
10/12/2014 TS.BS DO QUANG HUAN 
10/12/2014 TS.BS DO QUANG HUAN 
Recent Coronary IVUS Progression Trials 
-1.2 
-0.6 
0 
0.6 
1.2 
1.8 
50 60 70 80 90 100 110 120 
Median 
Change 
In Percent 
Atheroma 
Volume 
(%) 
Mean Low-Density Lipoprotein Cholesterol (mg/dL) 
REVERSAL 
pravastatin 
REVERSAL 
atorvastatin 
CAMELOT 
placebo 
A-Plus 
placebo 
ACTIVATE 
placebo 
Relationship between LDL-C and Progression Rate 
ASTEROID 
rosuvastatin 
r
2
= 0.95 
p<0.001 
Nissen S. JAMA 2006 
Lipids 
Safety 
Lipids 
CRP 
Safety 
Lipids 
CRP 
Safety 
Patients (n=825) 
18–75 years 
Hospitalised for ACS (STEMI, 
NSTEMI, UA) within 48hrs of 
ischaemic symptoms 
PCI, Lysis, or Medical treatment 
Rosuvastatin 40 mg (n=270) 
Atorvastatin 80 mg (n=278) 
Rosuvastatin 20 mg (n=277) 
Visit: 
Week: 
1 
4 
6 
5 
12 
2 
0 
3 
2 
Screening / baseline 
blood analysis 
LUNAR 
Study Design 
Prospective, multi-centre, randomised, open-label, parallel-group 
phase IIIb study 
Symptom 
Onset 
Average time from symptom onset to 
study drug treatment = 3.9 days 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
Lipids 
Safety 
Lipids 
CRP 
Safety 
Lipids 
CRP 
Safety 
Patients (n=825) 
18–75 years 
Hospitalised for ACS (STEMI, NSTEMI, 
UA) within 48hrs of ischaemic symptoms 
Rosuvastatin 40 mg (n=270) 
Atorvastatin 80 mg (n=278) 
Rosuvastatin 20 mg (n=277) 
Visit: 
Week: 
6 
12 
0 
2 
Screening / baseline 
blood analysis 
LUNAR 
Study Design 
Symptom 
Onset 
Average time from symptom onset to 
study drug treatment = 3.9 days 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
Variable 
Rosuvastatin 
20 mg/day 
(n=246) 
Rosuvastatin 
40 mg/day 
(n=251) 
Atorvastatin 
80 mg/day 
(n=257) 
LDL-C (mg/dL) 138.4 138.8 133.2 
HDL-C (mg/dL) 39.5 38.8 39.9 
Non–HDLC (mg/dL) 161.2 162.8 156.0 
Total cholesterol (mg/dL) 200.7 201.7 195.9 
Triglycerides, mg/dL 180.8 182.7 157.5 (n = 254) 
LDL-C / HDL-C 3.68 3.77 3.59 
Non–HDL-C / HDL-C 4.32 4.46 4.25 
TC / HDL-C 5.32 5.46 5.25 
Apo B (mg/dL) 130.0 (n=223) 132.2 (n=224) 127.4 (n=231) 
Apo A-I (mg/dL) 134.6 (n=223) 134.0 (n=224) 135.3 (n=231) 
Apo B / Apo A-I 1.00 (n=223) 1.01 (n=224) 0.97 (n=231) 
hs-CRP* 12.3 (n=238) 12.9 (n=241) 12.3 (n=249) 
* Median value 
LUNAR 
Baseline Characteristics 
LDL-C = low density lipoprotein cholesterol, HDL-C = high density lipoprotein cholesterol, TC = 
total cholesterol, Apo=apolipoprotein, hs-CRP = high sensitivity C-reactive protein 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
* 
Average 
change in 
LDL-C 
from 
baseline 
(%) 
Rosuvastatin 
20 mg 
Rosuvastatin 
40 mg 
Atorvastatin 
80 mg 
LUNAR 
Primary Endpoint 
*p< 0.05 versus atorvastatin 80 mg 
Similar results were achieved in all subcategories of ACS (unstable angina, 
non-STEMI, and STEMI) 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
average of Week 6 and Week 12 data 
* 
Average 
change in 
LDL-C 
from 
baseline 
(%) 
Rosuvastatin 
20 mg 
Rosuvastatin 
40 mg 
Atorvastatin 
80 mg 
LUNAR 
Primary Endpoint 
*p< 0.05 versus atorvastatin 80 mg 
Similar results were achieved in all subcategories of ACS (unstable angina, non-STEMI, and STEMI) 
average of Week 6 and Week 12 data 
** 
Mean change in 
HDL-C from 
baseline (%) 
Rosuvastatin 
20 mg 
Rosuvastatin 
40 mg 
Atorvastatin 
80 mg 
*** 
LUNAR 
Secondary Endpoint 
**p< 0.01, *** p<0.001 versus atorvastatin 80 mg 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
 LUNAR 
Safety & Tolerability 
Variable 
Rosuvastatin 
20 mg/day 
(n=267) 
Rosuvastatin 
40 mg/day 
(n=263) 
Atorvastatin 
80 mg/day 
(n=269) 
Any Serious AE* 
28 (10.5%) 
23 (8.7%) 
38 (14.1%) 
Serious Cardiovascular AE* 
9 (3.4%) 
5 (1.9%) 
6 (2.2%) 
Unstable angina 4 (1.5%) 3 (1.1%) 3 (1.1%) 
Myocardial infarction 5 (1.9%) 2 (0.8%) 2 (0.7%) 
Cerebrovascular accident 0 0 1 (0.4%) 
Withdrawal due to AE 
10 (3.7%) 
16 (6.1%) 
25 (9.3%) 
Musculoskeletal and connective tissue 
disorders 
5 (1.9%) 6 (2.3%) 17 (6.3%) 
Death* 
0 
2 (0.8%) 
1 (0.4%) 
AE = adverse event 
*None of the serious AEs, serious cardiovascular AEs or deaths were considered by the investigators to be related to study treatment 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
 LUNAR 
Safety & Tolerability 
Variable 
Rosuvastatin 
20 mg/day 
(n=267) 
Rosuvastatin 
40 mg/day 
(n=263) 
Atorvastatin 
80 mg/day 
(n=269) 
Any Serious AE* 
28 (10.5%) 
23 (8.7%) 
38 (14.1%) 
Serious Cardiovascular AE* 
9 (3.4%) 
5 (1.9%) 
6 (2.2%) 
Unstable angina 4 (1.5%) 3 (1.1%) 3 (1.1%) 
Myocardial infarction 5 (1.9%) 2 (0.8%) 2 (0.7%) 
Cerebrovascular accident 0 0 1 (0.4%) 
Withdrawal due to AE 
10 (3.7%) 
16 (6.1%) 
25 (9.3%) 
Musculoskeletal and connective tissue 
disorders 
5 (1.9%) 6 (2.3%) 17 (6.3%) 
Death* 
0 
2 (0.8%) 
1 (0.4%) 
AE = adverse event 
*None of the serious AEs, serious cardiovascular AEs or deaths were considered by the investigators to be related to study treatment 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
Variable 
Rosuvastatin 
20 mg/day 
Rosuvastatin 
40 mg/day 
Atorvastatin 
80 mg/day 
Serum creatinine, μmol/L 
(n=266) (n=263) (n=269) 
Baseline, mean (SD) 88.5 (16.2) 87.0 (16.0) 90.1 (17.4) 
(n=220) (n=202) (n=210) 
Change at final visit, mean (SD) 6.3 (12.0) 4.9 (11.2) 5.8 (14.3) 
eGFR, mL/min/1.73 m2 
(n=266) (n=263) (n=269) 
Baseline, mean (SD) 81.9 (15.7) 83.5 (17.0) 81.7 (17.1) 
(n=220) (n=202) (n=210) 
Change at final visit, mean (SD) −6.6 (12.6) −5.3 (11.5) −6.5 (13.4) 
LUNAR 
Safety & Tolerability 
SD = standard deviation 
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015 
10/12/2014 TS.BS DO QUANG HUAN 
Lipid Management 
High-intensity statin therapy should be initiated or continued in all 
patients with STEMI and no contraindications to its use. 
It is reasonable to obtain a fasting lipid profile in patients with 
STEMI, preferably within 24 hours of presentation. 
I IIa IIb III 
I IIa IIb III 
2013 ACCF/AHA Guideline for the 
Management of ST-Elevation Myocardial 
Infarction 
KẾT LUẬN 
1- Phản ứng viêm là nguyên nhân làm vỡ mảng xơ vữa: 
 dẫn đến kết tập tiểu cầu, tạo huyết khối gây nên HCVC 
 Phản ứng viêm  xơ hoá cơ tim nhiều hơn 
2- Statin liều cao trên những BN bị HCVC làm giảm phản ứng 
 viêm , kháng kết tập tiểu cầu, kháng đông, dãn mao mạch vành, và 
 giảm biến cố tim mạch 
3- Khuyến cáo ESC, ACC, AHA : sử dụng Statin liều cao trên BN 
 HCVC 
 ( Rosuvastatin 40mg làm giảm p/ư viêm , giảm biến cố TM sau 
 HCVC và làm giảm nhanh LDL-C hơn so với Atorvastatin) 
10/12/2014 DO QUANG HUAN, MD, PhD, FACC, FSCAI