Drug Eluting Balloon in Acute Myocardial Infarction:

1
Drug Eluting Balloon in Acute Myocardial
Infarction
6 month results of the DEB-AMI study
(ClinicalTrials.gov numberNCT00856765)

• On behalf of the DEB-AMI study group (PI)
• P.R. Stella, MD, PhD
• p.stella_at_umcutrecht.nl

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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

• Scientific Advisory Board

• Eurocor, Bonn, Germany

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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)

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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

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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 _at_ 6 month F.U.
BMS _at_ 4 months
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Study Methods

• Two-center randomized international prospective
  study comparing BMS vs DEBBMS vs DES in STEMI
• Computer generated sequences randomization in
  111 ratio comparison between DES, BMS and
  DEBBMS
• Same drug (Paclitaxel) as in the DEB for DES
• Independent DSMB/CEC, Corelab (QCA, OCT, ACT)

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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 gt 1

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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 lt2.5 and gt4.0 mm
• Target lesion length gt25 mm
• Intolerance for aspirin or clopidogrel
• Life expectancy lt 12 month
• Women with child bearing potential

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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)

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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 0.05
• 43 patients per group are needed
• Accommodated for Loss to follow-up of
  approximately 15 50p/gr

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DIOR-II Technology

• Paclitaxel balloon surface 3 µg/mm²
• Coating method is a 11 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. _at_
  nominal balloon pressure

The optical refraction of Shellac gives balloon a
shiny appearance
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Procedure flowchart
Primary PCI for STEMI
Thrombosuction (TIMI gt 1)
Randomization
BMS
DEB BMS
DES
6-month clinical and angiographic FU
6-month clinical and angiographic FU
6-month clinical and angiographic FU
OCTAcethylcholine endothelial testing
OCTAcethylcholine endothelial testing
OCTAcethylcholine endothelial testing
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ResultsBaseline patient characteristics
BMS N50 DEB N50 DES N49 P Value DEB vs. BMS
Age (years) 59.910.9 59.79.9 55.99.7 0.92
Male gender 42 (82.4) 41 (82.0) 41 (83.7) 0.96
Risk factors
Diabetes mellitus 6 (11.8) 3 (6.0) 2 (4.1) 0.49
Hyperlipidemia 11 (21.6) 13 (26.0) 16 (32.7) 0.60
Current smoker 29 (56.9) 19 (38.0) 28 (57.1) 0.07
Hypertension 18 (35.3) 17 (34.0) 15 (30.6) 0.89
Previous myocardial infarction 0 1 (2.0) 2 (4.1) 0.50
Target vessel 0.16
Left anterior descending/diagonal 21 (41.2) 24 (48.0) 18 (36.7)
Circumflex/marginal branch 8 (15.7) 13 (26.0) 11 (22.4)
Right coronary artery/posterior descending 22 (43.1) 13 (26.0) 20 (40.1)
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Results Baseline procedural characteristics
  BMS N50 DEB N50 DES N49 P Value DEB vs. BMS
Number of lesions treated       0.72
1 48 (94.1) 46 (92.0) 49 (100)  
2 3 (5.9) 4 (8.0) 0  
Predilatation 50 (100) 30 (60) 49 (100) lt0.001
DEB diameter, mm - 2.720.61 - -
DEB length, mm - 23.43.7 - -
DEB pressure, atm - 10.93.3 - -
DEB inflation time, s - 44.114.4 - -
Number of stents implanted per patient 1.290.50 1.260.66 1.200.46 0.77
Stent diameter, mm 2.940.54 2.980.52 2.880.44  
Total stent length, mm 25.310.8 24.413.4 25.413.3 0.69
Glycoprotein IIB/IIIA inhibitor 41 (80.4) 43 (86.0) 39 (79.6) 0.64
Contrast use ml 182.847.5 200.766.5 170.862.1 0.12
Fluoroscopy time, min 10.78.7 16.019.6 9.87.8 0.08
Procedural time, min 51.318.4 57.523.7 45.021.3 0.15
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Results Baseline angiographic characteristics
  BMS N50 DEB N50 DES N49 P Value DEB vs. BMS
Pre-procedure        
Reference vessel diameter, mm 2.840.58 2.840.41 2.780.53 0.99
Minimal luminal diameter, mm 0.740.36 0.620.32 0.640.38 0.09
Diameter stenosis, 74.111.8 78.811.9 77.312.8 0.05
Lesion length, mm 16.209.1 18.713.1 16.88.7 0.28
Post-procedure        
Minimal luminal diameter, mm 2.470.51 2.500.49 2.530.41 0.75
Diameter stenosis () 14.17.8 14.19.6 12.28.6 1
Measured after opening culprit lesion
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Results angiographic 6-month follow-up
BMS N42 DEB N42 DES N43 P Value DEB vs. BMS
Late luminal loss, mm 0.780.59 0.640.56 0.210.32 0.25
Minimal luminal diameter, mm 1.680.75 1.860.74 2.310.42 0.25
Diameter stenosis, 41.223.5 35.720.9 19.011.6 0.26
Binary restenosis 11 (26.2) 12 (28.6) 2 (4.7) 0.86
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Results Clinical outcomes
BMS N50 DEB N50 DES N49 P Value DEB vs. BMS
Cardiac death 2 (3.9) 0 0 0.16
Non cardiac death 0 0 0 -
Myocardial infarction 0 1 (2.0) 0 0.50
Target lesion revascularization 9 (17.6) 10 (20.0) 1 (2.0) 0.76
Target-vessel revascularization 1 (2.0) 1 (2.0) 1 (2.0) 0.99
Stent thrombosis (4 and 5 days) 0 2 (4.0) 0 0.15
Major adverse cardiac events 12 (23.5) 10 (20.0) 2 (4.1) 0.67
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OCT Results at FU
  BMS N10 DEB N12 DES N10 P Value DEB vs. BMS P Value DEB vs. DES
Cross-section analyses          
Stent length analyzed 26.99.0 24.910.2 22.4211.5 0.67 0.63
Minimum lumen area, mm2 3.461.92 3.212.06 5.761.89 0.79 0.01
Mean lumen area, mm2 5.902.43 5.692.36 8.061.34 0.86 0.02
Maximum neointimal area, mm2 6.742.69 4.900.88 2.961.28 0.06 0.001
Mean neointimal area, mm2 4.141.61 2.860.89 1.320.58 0.05 lt0.001
Lumen volume, mm3 151.275.6 132.054.7 173.274.7 0.54 0.19
Stent volume, mm3 259.6114.1 197.667.2 202.796.6 0.17 0.90
Neointimal volume, mm3 108.348.8 65.628.1 29.423.9 0.03 0.008
Strut analyses          
Total no. struts analyzed 3530 5795 4938 0.38 0.85
Covered embedded struts, 98.72.87 94.95.57 82.615.6 0.10 0.02
Covered protruding struts, 0.611.20 2.012.23 11.710.0 0.08 0.004
Uncovered struts, 0.110.32 1.322.64 2.263.50 0.08 0.16
Malapposed struts, 0.561.40 1.742.08 3.473.62 0.06 0.22
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ResultsAcetylcholine
BMS vs. DES P0.03 P0.02 Rest NS
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Summary

• The use of DEBBMS 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 gtgt DEBBMS

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However . . . .
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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

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Discussion 1 Effect of Predilatation in DEB
P0.04
(60)
(40)
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Discussion 2DEB-TLR/MACE
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Discussion 3clinically vs. non clinically driven
TLR outcomes
BMS 11.1 Nonclinically driven DEB 30.0
Nonclinically driven
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Discussion 4Expert DEB-operator vs. Mean of all
operators
P0.33
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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 (OCTAch),
  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.

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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

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