High dose statin loading in ACS – Short & long term outcomes benefit

ing in ACS– 
short & long term outcomes benefit 
Cholesterol Management 
Class I 
High-intensity statin therapy should be initiated or 
continued in all patients with NSTE-ACS and no 
contraindications to its use. (Level of Evidence: A) 
Class IIa 
It is reasonable to obtain a fasting lipid profile in patients with 
NSTE-ACS, preferably within 24 hours of presentation. 
(Level of Evidence: C) 
2014 AHA/ACC Guideline for the Management of 
Patients With Non–ST-Elevation ACS 
Lipid Management: Recommendations 
CLASS I 
High-intensity statin therapy should be initiated or 
continued in all patients with STEMI and no contraindications 
to its use. (Level of Evidence: B) 
CLASS IIa 
It is reasonable to obtain a fasting lipid profile in patients with 
STEMI, preferably within 24 hours of presentation. (Level of 
Evidence: C) 
2013 ACCF/AHA Guideline for the Management of 
ST-Elevation Myocardial Infarction 
 771 pts with 
 NSTE-ACS 
 sent to 
 early coronary 
 angiography 
 (<48 hours) 
 R
an
d
o
m
iz
at
io
n
 (
N
=1
9
1
) 
Atorvastatin 80 mg 
12 hrs pre-angio; 
 further 40 mg 
2 hrs before 
N=96 
Coronary 
angiography 
Placebo 
12 hrs pre-angio; 
 further 
dose 2 hrs 
 before 
N=95 
Primary 
combined 
end point: 
30-day 
death, MI, 
TVR 
1st blood sample 
(pre-PCI) 
CK-MB, troponin-I, myoglobin, CRP 
ARMYDA-ACS trial: Study design 
2nd and 3rd 
blood samples 
(8 and 24 hrs 
post-PCI) 
30 days 
580 pts excluded for: 
 - 451 statin therapy 
 - 41 emergency angiography 
 - 43 LVEF <30% 
 - 30 contraindications to statins 
 - 15 severe renal failure 
 PCI 
atorvastatin 
 N=86 
 PCI 
 placebo 
 N=85 
20 pts excluded for indication to: 
 - medical therapy (N=8) 
 - bypass surgery (N=12) 
atorvast 
Patti G, J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. 
 Individual and Combined Outcome Measures 
of the Primary End Point at 30 days 
 ARMYDA-ACS results 
0
3
6
9
12
15
18
21
Death MI TVR MACE
Atorvastatin Placebo
4/86 
(5%) 
13/85 
(15%) 
1/85 
(2%) 
14/85 
(17%) 
4/86 
(5%) 
P=0.04 
P=0.01 
% 
Composite 
Primary End Point 
Patti G, J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. 
ARMYDA-ACS: CONCLUSIONS 
1. Even a short-term atorvastatin pretreatment prior to PCI 
may improve outcome in patients with Unstable Angina and 
NSTEMI; mostly driven by a reduction of peri-procedural MI 
(70% risk reduction) 
2. Lipid-independent pleiotropic actions of atorvastatin may 
explain such effect 
3. These findings may support the indication of “upstream” 
administration of high dose statins in patients with Acute 
Coronary Syndromes treated with early invasive strategy 
Patti G, J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. 
 Individual and Combined Outcome Measures 
of the Primary Endpoint at 30 days 
8.6 
9.1 
P=0.045 
% 
Composite 
Primary End Point 
3.4 
0 
3 
6 
9 
12 
Cardiac 
death 
MI TVR MACE 
Atorvastatin 
Placebo 
0.5 0.5 
3.4 
Di Sciasio G. J Am Coll Cardiol 2009 Aug 4;54(6):558-65 
The primary end point was 30-days 
composite primary end point of death, 
myocardial infarction, 
and target vessel revascularization 
6.7
15.9
0
2
4
6
8
10
12
14
16
18
Rosuvastatin Control
MACEs (30 days)MACEs (%)
RRR 63%
p=0.002
• 445 ACS patients who underwent PCI 
• Control group (n=220, 63±11 years, 
male 62%) 
• Statin group of 40 mg rosuvastatin 
loading before PCI (n=225, 64±10 
years, male 60%) 
• Incidence of peri-procedural 
myocardial injury was assessed by 
analysis of CK-MB & cardiac troponin T 
before PCI, at 6 h and the next 
morning after PCI. 
12-month follow-up results of high dose rosuvastatin 
loading before PCI in patients with ACS 
Methods: 
MACE including cardiac death, non-fatal MI, non-fatal stroke, & any 
ischemia-driven revascularization, was assessed after 12 months 
Results: 
• In 11±3 months of follow-up, MACE occurred in 20.5% of patients 
in control group vs. 9.8% in rosuvastatin group (p=0.002) 
• The incidence of death and non-fatal MI was significantly greater 
in control group than in rosuvastatin group (p=0.021) 
• Multivariate analysis revealed that rosuvastatin loading was an 
independent predictor of a reduction in the risk of MACE at 12 
months (p=0.006) 
Yun KH, et al, Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.04.052 
Yun KH, et al, Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.04.052 
12- month MACE in patients with ACS who received 
no rosuvastatin or high dose rosuvastatin loading before PCI 
To compare a reloading dose of Rosuvastatin 40mg and 
Atorvastatin (80mg) administered within 24h before the procedure 
in reducing the rate of periprocedural myonecrosis (CKMB>3ULN) 
in patients on chronic statin treatment 
CK-MB 
MACE 
ACSIS study - STATINS LOADING BEFORE PPCI 
 • to evaluate the 
“real world” effect 
of statin loading 
prior to PPCI in 
506 STEMI 
patients 
undergoing PPCI 
• Statin loading was 
administered 
before PPCI to 137 
patients (27%) and 
369 patients (73%) 
did not receive a 
statin before PPCI. 
Early statin loading was associated with more 
frequent early STR > 70% (81% vs. 67, p= 0.005). 
Statin loading prior to PPCI remained independent 
predictor of early STR (OR 2.97, CI 1.62-5.45, 
p=0.00005) in multivariable analysis 
Diego Medvedofsky. J Am Coll Cardiol. 2013;61(10_S):. doi:10.1016/S0735 1097(13)60066-2 
Young-Guk Ko, Am J Cardiol 2014;114:29-35 
1. Serial MRI data were available for 121 patients 
2. The relative infarct volumes in the acute and chronic phases 
were not different between the groups 
3. No differences between groups were observed for peri-procedural 
micro-vascular circulation evaluated by TIMI flow grade, 
myocardial blush grade, ST-segment resolution, micro-vascular 
obstruction on cardiac MRI, or clinical outcomes. 
4. Early high-dose rosuvastatin therapy in patients with STEMI 
undergoing PPCI did not improve peri-procedural myocardial 
perfusion or reduce infarct volume measured by MRI compared 
with the conventional low-dose rosuvastatin regimen 
ROSEMARY study main findings 
Young-Guk Ko, Am J Cardiol 2014;114:29-35 
Alexandre M. Benjo, Catheterization and Cardiovascular Interventions 85:53–60 (2015) 
Evaluate the incidence of peri-procedure MI and MACE including 
spontaneous MI, death, and TVR of statin naïve patients presenting 
with stable angina or NSTE-ACS and treated with statins prior to PCI. 
High dose statin therapy given prior to PCI in 
patients with NSTE-ACS is associated with a 
reduction in pMI and short-term clinical events 
Alexandre M. Benjo, Catheterization and Cardiovascular Interventions 85:53–60 (2015) 
• 1,591 patients were given loading dose of 
statin before PCI 
• 1,555 patients were given statin therapy 
initiated only after the PCI. 
• Statin loading prior to PCI was associated 
with a 56% RR in pMI (OR: 0.44, 
P<0.00001). 
• 41% reduction in clinical events patients 
treated with statin loading prior to PCI 
(OR: 0.59, P=0.02). 
• Results were only significant for those 
patients with NSTE-ACS (OR: 0.18, 
P=0.0005) and was not noted in the group 
of patients who underwent PCI for stable 
angina (OR: 0.92, P =0.78). 
Main findings from the meta-analysis 
(1,210 articles, 14 RCTS, 3,146 patients) 
Alexandre M. Benjo, Catheterization and 
Cardiovascular Interventions 85:53–60 (2015) 
High-dose RSV preloading significantly improve myocardial perfusion 
& reduce 58% MACE (P < 0.00001), 60% PMI (P < 0.0001) 
in patients undergoing PCI 
Not only stable angina and ACS patients but also statin naïve and 
previous statin therapy patients 
IBIS-4 study: High-intensity rosuvastatin therapy over 13 months is 
associated with regression of coronary atherosclerosis in non-infarct-
related arteries among STEMI patients. 
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Raber L, et al. European Heart Journal 2014; 1-11. doi:10.1093/eurheartj/ehu373 
Lumen 
Area 
Plaque Area 
Baseline 
Plaque Area 
Lumen 
Area 
Follow up 
Rosuva 40mg 
Thể tích 
mảng XV toàn bộ 
đoạn khảo sát 
Thể tích mảng 
XV đoạn 10 
mm nặng nhất 
p<0.001 
-2 
-1 
0 
p value: follow-up vs. baseline 
-2.94 
P=0.007 
-0.9 
%
 T
h
a
y
 đ
ổ
i 
tr
u
n
g
 b
ìn
h
-3 
Intravascular Ultrasound-Derived Measures of Coronary 
Atherosclerotic Plaque Burden and Clinical Outcome 
Nicholls SJ, et al. J Am Coll Cardiol 2010;55:2399–407 
A direct relationship was observed between the burden of coronary 
atherosclerosis, its progression, and adverse cardiovascular events 
Statin-naive & Early Invasive Strategy NSTE-ACS patients 
Coronary Angiography ± PCI 
Hydration, N-Acetylcystein 
Early high-dose Rosuvastatin for CIN Prevention in ACS 
The PRATO-ACS study design 
CCU-Admission 
Contrast 
CI-AKI 
Controls Rosuvastatin 
40 mg (LD) then 20 mg/day 
R 
Primary Endpoint: 
↑ Cr ≥ 0.5 mg/dl or ≥ 25 % within 72 hrs of contrast 
exposure 
~
 2
4
 H
7
2
 H
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
PRATO-ACS: CI-AKI Primary Endpoint 
& Adverse Clinical Events (30 days) 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Conclusions 
1. All those evidences strongly supports an ‘upstream’ administration 
of high-dose statins (atorvastatin 80 mg/ rosuvastatin 40 mg 
loading) in patients with ACS , especially to whom with an early 
invasive strategy. 
2. Not only statin naïve and but also previous statin therapy patients 
can get benefit from this treatment. 
3. High dose statin loading can help improve both short and long 
term outcomes for NSTE-ACS patients (less MACE- cardiac death, 
MI, TVR) 
4. High-dose rosuvastatin given on admission to statin-naïve patients 
who are scheduled for an early invasive strategy may help to 
prevent CI-AKI.