D rug E luting B alloon in A cute M yocardial I nfarction:

1. Drug Eluting Balloon in Acute Myocardial Infarction: 6 month results of the DEB-AMI study (ClinicalTrials.gov number:NCT00856765) On behalf of the DEB-AMI study group (PI) P.R. Stella, MD, PhD p.stella@umcutrecht.nl

2. Scientific Advisory Board Eurocor, Bonn, Germany Disclosure Statement of Financial Interest Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization listed below. Affiliation/Financial Relationship Company

3. Introduction • Primary PCI therapy of choice in STEMI • Inconsistent data BMS vs. DES • DES reduces TLR, no reduction ‘hard’ clinical endpoints • Impaired endothelial function and late malapposition with DES • Concerns about very late stent thrombosis (VLST)

4. Hypothesis for a DEB in STEMI ? • Local Drug Delivery to Vulnerable Plaque • Short exposure to Paclitaxel, resulting in potentially better endothelial healing • Less Restenosis than BMS • Less Late (Acquired-)Malapposition than DES • Preserved Endothelial Function

5. Why do we want a DEB in AMI ? DES: potential (very) late stent thrombosis BMS : Safe but high restenosis rates “Late malapposition” Acute Myocardial infarction DES @ 6 month F.U. BMS @ 4 months

6. Study Methods Two-center randomized international prospective study comparing BMS vs DEB+BMS vs DES in STEMI Computer generated sequences randomization in 1:1:1 ratio comparison between DES, BMS and DEB+BMS Same drug (Paclitaxel)asin the DEB for DES Independent DSMB/CEC, Corelab (QCA, OCT, ACT)

7. MethodsInclusion criteria Age: 18-80 year STEMI within 12 hours of onset of complaints Candidate for primary PCI with stent-implantation Successful thrombus aspiration defined by no angiographic signs of thrombus at the site of plaque rupture and TIMI flow > 1

8. MethodsExclusion criteria Unable to give written informed consent Previous PCI or CABG of infarct related vessel Left main stenosis ≥ 50% Triple vessel disease with stenosis ≥ 50% in 3 epicardial coronary arteries. Target vessel reference diameter <2.5 and >4.0 mm Target lesion length >25 mm Intolerance for aspirin or clopidogrel Life expectancy < 12 month Women with child bearing potential

9. Methods • Primary endpoint: • QCA-based late lumen loss at 6-month FU • Secondary endpoints at 6-month FU: • OCT-based stent malapposition • Endothelial function through acethylcholine testing • Clinical events (death, myocardial infarction, target lesion revascularization)

10. Poweranalysis Assumption of LLL (mean ± SD) at 6 month angiography between DEB/BMS versus BMS or DEB/BMS versus DES, 0.35 ± 0.5 mmversus 0.7 ± 0.5 mmor 0.35 ± 0.5 mmversus 0.1± 0.5 mm, respectively. A power of 0.90 and alfa of 0.05 43 patientsper group are needed Accommodated for Loss to follow-upof approximately 15% : 50p/gr

11. DIOR™-II Technology: • Paclitaxel balloon surface: 3 µg/mm² • Coating method is a 1:1 mixture of Paclitaxel (Ph Eur.) and Shellac (Ph Eur.) • Protection of wash off effect: drug hidden within the balloon folds • Delivery by simple diffusion • The Coating is CE marked • Shellac is well established in Cosmetics, as food coating and Tablet coating. • Shellac is recognized as safe (GRAS) by the FDA • Balloon inflation time recommended: 20-30 sec. @ nominal balloon pressure The optical refraction of Shellac gives balloon a shiny appearance

12. Procedure flowchart Primary PCI for STEMI Thrombosuction (TIMI > 1) Randomization DEB + BMS BMS DES 6-month clinical and angiographic FU 6-month clinical and angiographic FU 6-month clinical and angiographic FU OCT+Acethylcholine endothelial testing OCT+Acethylcholine endothelial testing OCT+Acethylcholine endothelial testing

13. ResultsBaseline patient characteristics

14. Results Baseline procedural characteristics

15. Results Baseline angiographic characteristics * Measured after opening culprit lesion

16. Results angiographic 6-month follow-up

17. Results Clinical outcomes

18. OCT Results at FU

19. ResultsAcetylcholine BMS vs. DES * P=0.03 # P=0.02 Rest NS

20. Summary The use of DEB+BMS in STEMI is: Feasible Primary endpoint 50% reduction late loss: Not reached Secondary endpoints (BMS vs DEB): No significant dif. OCT analysis in DEB arm: Better neointimal volumes however trend towards more malapposed struts Impaired endothelial function: DES >> DEB=BMS

21. However . . . .

22. Discussion Pre-dilatation in DEB was only done in 60% Difference in TLR and MACE / Center More non-clinically driven TLR in DEB than BMS Experienced DEB operator with better results

23. Discussion 1 Effect of Predilatation in DEB P=0.04 (60%) (40%)

24. Discussion 2DEB-TLR/MACE

25. Discussion 3clinically vs. non clinically driven TLR outcomes BMS: 11.1% Nonclinically driven DEB: 30.0% Nonclinically driven

26. Discussion 4Expert DEB-operator vs. Mean of all operators P=0.33

27. Conclusion I Use of DEB in DEB-AMI trial was safe and feasible but did not reach primary endpoint of 50% reduction late loss vs BMS DEBinduces morphological changes(OCT+Ach), however insufficient to result in superior angiographical and clinical changes with respect to BMS. DES induces more pronounced morphological changes (compared to DEB), resulting in superior angiographicalandclinical outcomes with respect to BMS and DEB.

28. Conclusion-II • The use of a DEB needs special dedication by operator • Further investigation necessary tooptimize results: pre-dilatation with POBA mandatory • Clinical follow-up DEB-AMI until 5 years

29. Food for thought Do we need to avoid BMS at all icw DEB? DEB-AMI 4th arm: DEB-only enrollment ongoing, results:TCT 2012

30. P. Agostoni A.Belkacemi H. Nathoe B.Hamer M. Voskuil F.Spano T.Wildbergh Y.Breuer G. Sangiorgi F. Politi M. Monopoli F. Sgurra Thank You !