STATINS PRE-PCI:
A Prospective, Randomized
Trial of Statins Prior to Stent
Implantation in Patients with
Stable Angina
Josef VESELKA
CardioVascular Center
University Hospital Motol
Prague, Czech Republic
veselka.josef@seznam.cz
Disclosure Statement
I, Josef Veselka DO NOT have a financial
interest/arrangement or affiliation with one
or more organizations that could be
perceived as a real or apparent conflict of
interest in the context of the subject of this
presentation.
Background
• Periprocedural non-Q MI (PMI) is a frequent
and prognostically important complication
of PCI.
• The available randomized studies suggest
that statins prevent PMI1-4.
1-2/ Briguori C. et al. EHJ 2004, JACC 2009
3/ DiSciascio G. et al. JACC 2009
4/ Pasceri V. et al., Circulation 2004
Mechanisms of Plaque Stabilization
• Thicken fibrous cap
• Remove lipids
• Reduce thrombosis
• Reduction of inflammation
• Improvement of endothelial
function
• Increase of NO bioavailability
Danesh RD, Kanwar YS. FASEB J 2004;18:805-15.
Pilot, non-randomized study
12% vs 20%
p = 0.04
OR 1.84
95% CI 1.1 to 3.2
400 consecutive pts.
with SAP treated by
PCI.
Statin group: 218 pts.
(81% pts. simvastatin 20
mg)
No statin group: 182
pts.
Pre-procedural statin therapy reduces risk and extent
of cardiac biomarker release following PCI.
Veselka J. et al. Heart Vessels 2006
Purpose
• The purpose of this randomized study
was to investigate, in stable angina
pectoris patients undergoing elective
PCI, the effect of two-day atorvastatin
(80 mg) therapy on the incidence of
PMI.
Design
Statin – NO
200 pts.
393 patients with SAP
Statin – YES
193 pts.
RANDOMIZATION 1:1
100 pts.
Atorvastatin 80 mg
2 day therapy, then PCI
100 pts.
Immediate PCI
193 pts.
Registry
Immediate PCI
TnI and CK-MB mass 16-24 hours after PCI
Sample size
The sample size was based on previous
studies1, 2 to demonstrate a reduction in
the primary end point from 18% in the
Control group to 5% in the Atorvastatin
group (two-sided chi square test, α = 0.05,
power = 0.83)
1/ Pasceri V. et al., Circulation 2004
2/ Veselka J. et al. Heart Vessels 2006
Inclusion / exclusion criteria
• Inclusion:
–
patients with stable angina pectoris or a
pathological exercise test
–
de-novo lesion 50 - 99% of luminal diameter
• Exclusion:
–
major diseases other than angina pectoris
–
acute coronary syndromes in the last two
weeks
End-point
• The primary end point of this study was
the incidence of PMI based on postinterventional release of Troponin I (TnI)
and creatine kinase-MB mass (CK-MB
mass).
• TnI and CK-MB mass values were considered
abnormal if they were elevated at least 3 times
ULN.
• Blood samples for TnI (CK-MB mass)
measurements were taken immediately prior to
PCI and 16-24 hours thereafter.
Patient characteristics at
randomization
Atorvastatin group
100 pts.
Control group
100 pts.
p value
68 ± 11
(44-91)
64 ± 10
(46-89)
0.006
54%
79%
< 0.001
Angina pectoris, class
(CCS)
2 ± 0.9
1.9 ± 0.8
0.28
History of myocardial
infarction
23%
27%
0.51
Current smokers
16%
23%
0.21
Hypertension
77%
65%
0.06
Diabetes
26%
25%
0.87
Age
(range)
Gender (male)
Patient characteristics at
randomization
Atorvastatin group
100 pts.
Control group
100 pts.
P value
Hypercholesterolemia > 5
mmol/l
40%
33%
0.30
Total plasma cholesterol
(mmol/l)
4.8 ± 1
4.6 ± 1.3
0.35
LDL-cholesterol (mmol/l)
3 ± 0.8
3±1
0.93
HDL-cholesterol (mmol/l)
1.1 ± 0.3
1.0 ± 0.3
0.37
Hypertriglyceridemia > 2
mmol/l
23%
14%
0.10
1.7 ± 0.9
1.5 ± 0.7
0.26
Plasma triglyceride (mmol/l)
Medication at randomization
Atorvastatin group
100 pts.
Control group
100 pts.
P value
Beta-blockers
63%
63%
1
Calcium channel
blockers
25%
15%
0.08
ACE inhibitors
43%
41%
0.77
Clopidogrel
27%
16%
0.06
Angiographic and interventional
characteristics
Atorvastatin group
100 pts.
Control group
100 pts.
Lesion located in LAD, RCA, LCx,
SVG, LMCA
One/two/three vessel disease
54/27/21/1/1%
53/18/29/0/0%
55/27/18%
63/23/14%
Type of lesion A/B1/B2/C lesions
15/29/38/18%
10/35/40/15%
Pre-PCI stenosis
82 ± 8%
84 ± 10%
Post-PCI stenosis
3 ± 10%
3 ± 12%
1%
2%
1.2 ± 0.1
1.1 ± 0.1
1.12
1.12
74
82
6.9 ± 4
6.7 ± 5
99%
97%
0
0
Intracoronary thrombosis
Number of treated lesions (mean)
Stents per patient (n)
Complete revascularization (%)
Mean fluoroscopic time (min)
Angiographic success
Q-wave MI within 24 hours (n)
All differences were not significant
Results
Incidence of PMI based on TnI release
After PCI (ng/ml)
(interquartile
range)
TnI > 3x ULN
Atorvastatin
group
100 pts.
Control group
100 pts.
Registry
193 pts.
p value
0.100
(0.096-0.385)
0.100
(0.060-0.262)
0.100
(0.100-0.270)
NS
17%
16%
12%
NS
Results
Incidence of PMI based on CK-MB mass release
After PCI (ng/ml),
(interquartile range)
CK-MB mass > 3x ULN
Atorvastatin
group
100 pts.
Control
group
100 pts.
Registry
193 pts.
p value
1.46
(0.83-2.52)
1.40
(0.90-2.54)
1.33
(0.73-2.40)
NS
10%
12%
10%
NS
Predictors of PMI based on TnI release
(multivariate analysis)
Variable
Odds ratio (95% CI)
P value
Age
1.026-1.159
0.006
Atorvastatin pre-treatment
0.365-3.488
0.834
Clopidogrel pre-treatment
0.525-7.191
0.320
Diabetes mellitus
0.055-1.134
0.072
Total cholesterol
0.956-2.837
0.072
Beta-blockers
0.175-1.793
0.329
Degree of stenosis
0.966-1.090
0.392
Length of stents
0.957-1.083
0.569
Complex lesion
0.038-1.491
0.126
Conclusion
The results of this study demonstrate
that in stable patients undergoing PCI,
pretreatment with atorvastatin (80 mg)
for 48 hours preceding PCI is not
associated with a different incidence of
PMI.
A large, international, statistically robust, randomized trial
addressing the dose, duration, and type of statin is
necessary to settle the issue of routine administration
(reload) of statins prior to acute or elective PCI.
Acknowledgement
Co- authors:
D. Zemánek, MD, P. Hájek, MD, M. Malý, MD, PhD, R. Adlová, MD, L.
Martinkovičová, MD, D. Tesař, MD, PhD.
Statisticians:
E. Hansvenclová, M. Malý
Staff of the Dept. of Cardiology, University Hospital Motol, Prague, CZ