STATINS PRE-PCI : A Prospective, Randomized Trial of Statins Prior to Stent Implantation in Patients with Stable Angina

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 VeselkaDO NOThave 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 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

4. Thicken fibrous cap Remove lipids Reduce thrombosis Reduction of inflammation Improvement of endothelial function Increase of NO bioavailability Mechanisms of Plaque Stabilization Danesh RD, Kanwar YS. FASEB J 2004;18:805-15.

5. 12% vs 20% p = 0.04 OR 1.84 95% CI 1.1 to 3.2 Pilot, non-randomized study 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

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

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

12. Patient characteristics at randomization

13. Medication at randomization

14. Angiographic and interventional characteristics All differences were not significant

15. Results Incidence of PMI based on TnI release

16. Results Incidence of PMI based on CK-MB mass release

17. Predictors of PMI based on TnI release(multivariate analysis)

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 thedose, duration, and type of statin is necessary to settle the issue of routineadministration (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