1. 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

2. 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.

3. Background Periprocedural non-Q MI (PMI) is a frequent and prognostically important complication of PCI. The available randomized studies suggest that statins prevent PMI 1-4. 1-2/ Briguori C. et al. EHJ 2004, JACC 2009 3/ DiSciascio G. et al. JACC 2009 4/ Pasceri V. et al., Circulation 2004

4. 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.

5. 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

6. 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.

7. Design 393 patients with SAP Statin – YES 193 pts. Statin – NO 200 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

8. Sample size The sample size was based on previous studies 1, 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

9. 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

10. 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.

11. Patient characteristics at randomization Atorvastatin group 100 pts. Control group 100 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 ± 0.91.9 ± 0.80.28 History of myocardial infarction 23%27%0.51 Current smokers16%23%0.21 Hypertension77%65%0.06 Diabetes26%25%0.87

12. 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 ± 14.6 ± 1.30.35 LDL-cholesterol (mmol/l)3 ± 0.83 ± 10.93 HDL-cholesterol (mmol/l)1.1 ± 0.31.0 ± 0.30.37 Hypertriglyceridemia > 2 mmol/l 23%14%0.10 Plasma triglyceride (mmol/l)1.7 ± 0.91.5 ± 0.70.26

13. Medication at randomization Atorvastatin group 100 pts. Control group 100 pts. P value Beta-blockers63% 1 Calcium channel blockers 25%15%0.08 ACE inhibitors43%41%0.77 Clopidogrel27%16%0.06

14. Angiographic and interventional characteristics Atorvastatin group 100 pts. Control group 100 pts. Lesion located in LAD, RCA, LCx, SVG, LMCA 54/27/21/1/1%53/18/29/0/0% One/two/three vessel disease55/27/18%63/23/14% Type of lesion A/B1/B2/C lesions15/29/38/18%10/35/40/15% Pre-PCI stenosis82 ± 8%84 ± 10% Post-PCI stenosis3 ± 10%3 ± 12% Intracoronary thrombosis1%2% Number of treated lesions (mean)1.2 ± 0.11.1 ± 0.1 Stents per patient (n)1.12 Complete revascularization (%)7482 Mean fluoroscopic time (min)6.9 ± 46.7 ± 5 Angiographic success99%97% Q-wave MI within 24 hours (n)00 All differences were not significant

15. Results Atorvastatin group 100 pts. Control group 100 pts. Registry 193 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 Incidence of PMI based on TnI release

16. Results Atorvastatin group 100 pts. Control group 100 pts. Registry 193 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 Incidence of PMI based on CK-MB mass release

17. Predictors of PMI based on TnI release (multivariate analysis) VariableOdds ratio (95% CI)P value Age1.026-1.1590.006 Atorvastatin pre-treatment0.365-3.4880.834 Clopidogrel pre-treatment0.525-7.1910.320 Diabetes mellitus0.055-1.1340.072 Total cholesterol0.956-2.8370.072 Beta-blockers0.175-1.7930.329 Degree of stenosis0.966-1.0900.392 Length of stents0.957-1.0830.569 Complex lesion0.038-1.4910.126

18. 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.

19. 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