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

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

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)

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

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

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) Same drug (Paclitaxel) as in the DEB for DES Independent DSMB/CEC, Corelab (QCA, OCT, ACT)

Methods Inclusion criteria Age: 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

Methods Exclusion 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 4.0 mm Target lesion length >25 mm Intolerance for aspirin or clopidogrel Life expectancy < 12 month Women with child bearing potential

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)

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

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: nominal balloon pressure The optical refraction of Shellac gives balloon a shiny appearance

Procedure flowchart Primary PCI for STEMI Thrombosuction (TIMI > 1) BMSDEB + BMSDES 6-month clinical and angiographic FU OCT+Acethylcholine endothelial testing 6-month clinical and angiographic FU OCT+Acethylcholine endothelial testing Randomization 6-month clinical and angiographic FU OCT+Acethylcholine endothelial testing

Results Baseline patient characteristics BMS N=50 DEB N=50 DES N=49 P Value DEB vs. BMS Age (years)59.9± ± ± Male gender42 (82.4%)41 (82.0%)41 (83.7%)0.96 Risk factors Diabetes mellitus6 (11.8%)3 (6.0%)2 (4.1%)0.49 Hyperlipidemia11 (21.6%)13 (26.0%)16 (32.7%)0.60 Current smoker29 (56.9%)19 (38.0%)28 (57.1%)0.07 Hypertension18 (35.3%)17 (34.0%)15 (30.6%)0.89 Previous myocardial infarction01 (2.0%)2 (4.1%)0.50 Target vessel0.16 Left anterior descending/diagonal21 (41.2%)24 (48.0%)18 (36.7%) Circumflex/marginal branch8 (15.7%)13 (26.0%)11 (22.4%) Right coronary artery/posterior descending 22 (43.1%)13 (26.0%)20 (40.1%)

Results Baseline procedural characteristics BMS N=50 DEB N=50 DES N=49 P Value DEB vs. BMS Number of lesions treated (94.1%)46 (92.0%)49 (100%) 23 (5.9%)4 (8.0%)0 Predilatation50 (100%)30 (60%)49 (100%)<0.001 DEB diameter, mm-2.72± DEB length, mm-23.4±3.7-- DEB pressure, atm-10.9±3.3-- DEB inflation time, s-44.1± Number of stents implanted per patient1.29± ± ± Stent diameter, mm2.94± ± ±0.44 Total stent length, mm25.3± ± ± Glycoprotein IIB/IIIA inhibitor41 (80.4%)43 (86.0%)39 (79.6%)0.64 Contrast use ml182.8± ± ± Fluoroscopy time, min10.7± ± ± Procedural time, min51.3± ± ±

Results Baseline angiographic characteristics BMS N=50 DEB N=50 DES N=49 P Value DEB vs. BMS Pre-procedure Reference vessel diameter, mm2.84± ± ± Minimal luminal diameter, mm*0.74± ± ± Diameter stenosis, %*74.1± ± ± Lesion length, mm*16.20± ± ± Post-procedure Minimal luminal diameter, mm2.47± ± ± Diameter stenosis (%)14.1± ± ±8.61 * Measured after opening culprit lesion

Results angiographic 6-month follow-up BMS N=42 DEB N=42 DES N=43 P Value DEB vs. BMS Late luminal loss, mm0.78± ± ± Minimal luminal diameter, mm1.68± ± ± Diameter stenosis, %41.2± ± ± Binary restenosis11 (26.2%)12 (28.6%)2 (4.7%)0.86

Results Clinical outcomes BMS N=50 DEB N=50 DES N=49 P Value DEB vs. BMS Cardiac death2 (3.9%) Non cardiac death000- Myocardial infarction01 (2.0%)00.50 Target lesion revascularization9 (17.6%)10 (20.0%)1 (2.0%)0.76 Target-vessel revascularization1 (2.0%) 0.99 Stent thrombosis (4 and 5 days)02 (4.0%)00.15 Major adverse cardiac events12 (23.5%)10 (20.0%)2 (4.1%)0.67

OCT Results at FU BMS N=10 DEB N=12 DES N=10 P Value DEB vs. BMS P Value DEB vs. DES Cross-section analyses Stent length analyzed26.9± ± ± Minimum lumen area, mm23.46± ± ± Mean lumen area, mm25.90± ± ± Maximum neointimal area, mm2 6.74± ± ± Mean neointimal area, mm24.14± ± ± <0.001 Lumen volume, mm3151.2± ± ± Stent volume, mm3259.6± ± ± Neointimal volume, mm3108.3± ± ± Strut analyses Total no. struts analyzed Covered embedded struts, %98.7± ± ± Covered protruding struts, %0.61± ± ± Uncovered struts, %0.11± ± ± Malapposed struts, %0.56± ± ±

Results Acetylcholine BMS vs. DES * P=0.03 # P=0.02 Rest NS

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

However....

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

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

Discussion 2 DEB-TLR/MACE

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

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

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 DEB induces 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 angiographical and clinical outcomes with respect to BMS and DEB.

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

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

P. AgostoniA.Belkacemi H. NathoeB.Hamer M. VoskuilF.Spano T.WildberghY.Breuer G. Sangiorgi F. Politi M. Monopoli F. Sgurra