Liều nạp statin trong hội chứng vành cấp có thực sự đem lại lợi ích ngắn hạn và dài hạn

High dose statin loading in ACS–

short & long term outcomes benefit
Dinh Duc Huy, MD, FSCAI
Tam Duc Heart Hospital


2014 AHA/ACC Guideline for the Management of
Patients With Non–ST-Elevation ACS
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)


2013 ACCF/AHA Guideline for the Management of
ST-Elevation Myocardial Infarction
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)

ARMYDA-ACS trial: Study design
580 pts excluded for:
- 451 statin therapy
- 41 emergency angiography
- 43 LVEF <30%
- 30 contraindications to statins
- 15 severe renal failure

Patti G, J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8.

20 pts excluded for indication to:
- medical therapy (N=8)
- bypass surgery (N=12)

771 pts with
NSTE-ACS
sent to
early coronary
angiography
(<48 hours)

Randomization (N=191)

30 days

Atorvastatin 80 mg
12 hrs pre-angio;
further 40 mg

2 hrs before
N=96

PCI
atorvastatin
N=86
Coronary
angiography

Placebo
12 hrs pre-angio;
further
dose 2 hrs
before
N=95

atorvast

30-day
death, MI,
TVR

PCI
placebo
N=85

1st blood sample
(pre-PCI)

Primary

combined
end point:

2nd and 3rd
blood samples
(8 and 24 hrs
post-PCI)

CK-MB, troponin-I, myoglobin, CRP


ARMYDA-ACS results
Individual and Combined Outcome Measures
of the Primary End Point at 30 days
21 %
18

14/85
(17%)

13/85
(15%)

15

P=0.01

P=0.04

12

9

4/86
(5%)

4/86
(5%)

6

1/85
(2%)

3
0

Death
Atorvastatin

MI
Placebo

TVR

MACE
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.


12
%

Individual and Combined Outcome Measures
of the Primary Endpoint at 30 days
9.1

8.6

9

P=0.045

Atorvastatin

6

Placebo
3.4

3.4

3
0.5

0

Cardiac
death

0.5
MI

TVR

MACE

Di Sciasio G. J Am Coll Cardiol 2009 Aug 4;54(6):558-65

Composite
Primary End Point


The primary end point was 30-days

composite primary end point of death,
myocardial infarction,
and target vessel revascularization


• 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.

MACEs (30 days)

MACEs (%)

18
16
14
12
10
8
6
4
2

0

15.9

RRR 63%
p=0.002
6.7

Rosuvastatin

Control


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


12- month MACE in patients with ACS who received

no rosuvastatin or high dose rosuvastatin loading before PCI

Yun KH, et al, Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.04.052


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


ROSEMARY study main findings
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
Young-Guk Ko, Am J Cardiol 2014;114:29-35

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.

Alexandre M. Benjo, Catheterization and Cardiovascular Interventions 85:53–60 (2015)


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)


Main findings from the meta-analysis
(1,210 articles, 14 RCTS, 3,146 patients)
• 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
Alexandre M. Benjo, Catheterization and

angina (OR: 0.92, P =0.78).
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-infarctrelated arteries among STEMI patients.
Baseline
---------------------------------------------------------------------------------------------------------------------------------Thể tích
mảng XV toàn bộ
đoạn khảo sát

Plaque Area

Rosuva 40mg
Follow up

Lumen
Area

% Thay đổi trung bình

Lumen
Area

Thể tích mảng
XV đoạn 10
mm nặng nhất

0
-0.9
-1

P=0.007

-2
-3

-2.94
p<0.001
p value: follow-up vs. baseline

Plaque Area

Raber L, et al. European Heart Journal 2014; 1-11. doi:10.1093/eurheartj/ehu373


Intravascular Ultrasound-Derived Measures of Coronary
Atherosclerotic Plaque Burden and Clinical Outcome

A direct relationship was observed between the burden of coronary
atherosclerosis, its progression, and adverse cardiovascular events

Nicholls SJ, et al. J Am Coll Cardiol 2010;55:2399–407


Early high-dose Rosuvastatin for CIN Prevention in ACS
The PRATO-ACS study design
Statin-naive & Early Invasive Strategy NSTE-ACS patients

R

CCU-Admission

Rosuvastatin
~ 24 H

Controls

40 mg (LD) then 20 mg/day

Hydration, N-Acetylcystein
Contrast

Coronary Angiography ± PCI

72 H
CI-AKI

Primary Endpoint:
↑ Cr ≥ 0.5 mg/dl or ≥ 25 % within 72 hrs of contrast
exposure

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