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 financialinterest/arrangement or affiliation with

oneor 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 20093/ DiSciascio G. et al. JACC 20094/ 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

Pre-procedural statin therapy reduces risk and extent of cardiac biomarker release

following PCI.

400 consecutive pts. with SAP treated by PCI.

Statin group: 218 pts.(81% pts. simvastatin 20 mg)

No statin group: 182 pts.

Veselka J. et al. Heart Vessels 2006

12% vs 20%p = 0.04 OR 1.84 95% CI 1.1 to 3.2

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.

Design393 patients with SAP

Statin – YES193 pts.

Statin – NO200 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 20042/ 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 post-interventional 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 group100 pts.

Control group100 pts.

p value

Age(range)

68 ± 11(44-91)

64 ± 10(46-89)

0.006

Gender (male) 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

Patient characteristics at randomization

Atorvastatin group100 pts.

Control group100 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

Plasma triglyceride (mmol/l)

1.7 ± 0.9 1.5 ± 0.7 0.26

Medication at randomization

Atorvastatin group100 pts.

Control group100 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 group100 pts.

Lesion located in LAD, RCA, LCx, SVG, LMCA

54/27/21/1/1% 53/18/29/0/0%

One/two/three vessel disease 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%

Intracoronary thrombosis 1% 2%

Number of treated lesions (mean)

1.2 ± 0.1 1.1 ± 0.1

Stents per patient (n) 1.12 1.12

Complete revascularization (%) 74 82

Mean fluoroscopic time (min) 6.9 ± 4 6.7 ± 5

Angiographic success 99% 97%

Q-wave MI within 24 hours (n) 0 0

All differences were not significant

Results

Atorvastatin group

100 pts.

Control group

100 pts.

Registry193 pts.

p value

After PCI (ng/ml)(interquartile range)TnI > 3x ULN

0.100(0.096-0.385)

17%

0.100(0.060-0.262)16%

0.100(0.100-0.270)

12%

NS

NS

Incidence of PMI based on TnI release

Results

Atorvastatin group

100 pts.

Control group

100 pts.

Registry193 pts. p value

After PCI (ng/ml),(interquartile range)CK-MB mass > 3x ULN

1.46(0.83-2.52)

10%

1.40(0.90-2.54)

12%

1.33(0.73-2.40)

10%

NS

NS

Incidence of PMI based on CK-MB mass release

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