Martin Unverdorben

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The Paclitaxel-Eluting PTCA-Balloon Catheter in
Coronary Artery Disease PEPCAD II-ISR
Martin Unverdorben Rotenburg/Fulda, Germany and
Richmond, VA, USA Clinical Research Institute,
Center for Cardiovascular Diseases On behalf of
the PEPCAD II Investigators
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Presenter Disclosure Information
PEPCAD II 12-Month Follow-up
The following relationships exist related to this
presentation
M.Unverdorben Nothing to disclose B.Scheller Cons
ulting and lecture fees from BBraun, co-patent
owner of Sequent Please
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Agenda

• The PACCOCATH technology
• PEPCAD II ISR 6-month angiographic and clinical
  follow-up
• PEPCAD II ISR 12-month clinical follow-up

Statistics

• Descriptive statistics Mean SD
• Inferential statistics Students t-test,
  Fishers exact test, Logrank test
• Level of significance p lt 0.05

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DES vs. DEB (PACCOCATH)

• Slow and continuous drug release from stent
  struts
• 100 - 200 µg Paclitaxel Sirolimus
• Polymers with associated reactions
• Implies stent deployment

DES

• Instant and short term drug release from balloon
• 300 - 600 µg Paclitaxel
• No polymers
• Stenting optional

DEB
Scheller Heart 2007, 93 539-41
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The Matrix Coating
PACCOCATH technology creates a unique matrix
coating
pure paclitaxel
paclitaxel hydrophilic spacer
without
with PACCOCATH technology

• huge contact surface between lipophilic drug and
  the vessel wall
• high bioavailability of paclitaxel at the target
  site for rapid drug absorption by the vessel
  wall
• uniform/complete application of the drug after
  1st balloon expansion

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SeQuent (uncoated balloon)
SeQuent Please (coated balloon)
SeQuent Please (B.Braun Vascular Systems,
Berlin, Germany) is manufactured based on the
PACCOCATH technology with 3µg paclitaxel/mm² CE
mark filed in the EU
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• Objective
• Safety and efficacy of the Sequent Please DEB in
  the treatment of ISR in native coronary arteries
  (reference Ø ?2.5mm, ?3.5mm lesion length
  22mm) for procedural success and preservation of
  vessel patency in comparison to the Taxus DES

Study Design Prospective, randomized,
multi-center, two-arm phase-II pilot study
conducted in Germany
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• Primary Variable
• 6-month late lumen loss

• Secondary Variables
• Procedural success (30)
• 6-month binary restenosis rate
• 6-month MACE
• MACE at 1 and 3 years

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• Inclusion Criteria
• Stable or unstable angina (no MI)
• ISR in native coronary arteries

• Medication
• ASS 100 mg daily
• Clopidogrel 75 mg daily
• 3 months DEB
• 6 months DES

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Patients (ITT N131)

• DEB (N66)
  DES (N65) p
• Age years 64.69.7 65.18.7 0.7
• Male 48 (72.7) 50 (76.9) 0.7
• BMI kg/m2 27.9 4.6 28.64.2 0.4
• Serum cholesterol mg/dl 172 42 180 34
  0.3
• Serum LDL mg/dl 93 39 98 29
  0.4
• Diabetes mellitus 22 (33.3) 17 (26.2)
  0.4
• Current/ex-smokers 44 (66.7) 36 (55.4)
  0.3
• Hypertension 53 (80.3) 54 (83.1) 0.8
• Family history of CAD 21 (31.8) 22 (33.8)
  0.9
• Previous MI 37 (56.1) 28 (43.1) 0.2
• PAVD 9 (13.6) 7 (10.8) 0.8
• Serum crea mg/dL 1.1 1 1.0 0.2
  0.4

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Baseline Angiography (ITT N131)
DEB (N66) DES (N65) p
1-vessel disease 28.8 35.4
2-vessel disease 40.9 35.4 0.7
3-vessel disease 30.3 29.2
Stenosis length mm 15.7 ? 6.6 15.4 ? 6.6 0.8
Mehran I 31 (47.0) 25 (38.5)
Mehran II 20 (30.3) 26 (40.0) 0.7
Mehran III 14 (21.2) 12 (18.5)
Mehran IV 1 ( 1.5) 2 ( 3.1)
MLD pre PCI mm 0.74 ? 0.27 0.77 ? 0.30 0.6
Stenosis pre PCI 74 ? 9 73 ? 9 0.5
MLD post PCI mm 2.30 ? 0.40 2.56 ? 0.41 lt0.0001
Stenosis post PCI 20 ? 10 11 ? 8 lt0.001
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Outcome (ITT N131)
DEB (N66) DES (N65) p
Follow-up clinical months 6.2 0.9 6.2 0.9 1
Follow-up clinical N 64 (97.0) 65 (100) 0.5
Follow-up angiographic N 57 (86.4) 59 (90.8) 0.6
Late lumen loss mm 0.20 0.45 0.45 0.68 0.02
Binary restenosis in segment 4/57 (7.0) 12/59(20.3) 0.06
TLR 4/64 (6.3) 10/65 (15.4) 0.1
Myocardial infarction 0/64 (0.0) f1/65 (1.5) 1
Death 2/64 (3.1) 1/65 (1.5) 1
Total MACE (w/o noncardiac death) 5/64 (7.8) 11/65 (16.9) 0.2
1 each non-cardiac cardiac but not lesion
related non-cardiac death
fNSTEMI due to side branch occlusion
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As-Treated
Randomization N131
Sequent Please n66
Taxus n65
4 protocol violators Lesion too long
(41.1mm) Multilesion PCI in metal
jacket Significant flap after PCI Severe renal
failure
1 crossing failure treat/w convent balloon
4 crossing failure treat/w Sequent Please
66 DEB 56 DEB only 6 DEB BMS 4 DEB (cross-over)
60 DES 2 with additional DES
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Outcome (AsT N126)
DEB (N66) DES (N60) P
Follow-up clinical months 6.2 0.8 6.2 0.8 0.7
Follow-up clinical N 64 (97.0) 60 (100) 0.4
Follow-up angiographic N 58 (87.9) 54 (90.0) 0.8
Late lumen loss mm 0.19 0.38 0.47 0.71 0.03
Binary restenosis in segment 2/58 (3.4) 11/54 (20.4) 0.007
TLR 2/64 (3.1) 10/60 (16.7) 0.02
Myocardial infarction 0/64 (0.0) f1/60 (1.7) 1
Death 2/64 (3.1) 1/60 (1.7) 1
Total MACE (w/o noncardiac death) 3/64 (4.7) 11/60 (18.3) 0.02
fNSTEMI due to side branch occlusion
1 cardiac, not lesion related 2 non cardiac
non-cardiac death
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Event Free Survival (ITT/As-Treated)
p0.2 ITT
p0.03 As-Treated
Months post PCI
Logrank test
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12-Month Follow-up As-Treated
60 DES 2 with additional DES
66 DEB 56 DEB only 6 DEB BMS 4 DEB (cross-over)
Unknown today 1/66 (1.5)
Lost to FU 0/60 (0)
Unknown today 2/60 (3.3)
Lost to FU 1/60 (1.7)
Deaths 2/66 (3.0)
Deaths 3/60 (5)
Follow-up 12.30.8 months 57/60 (95.0)
Follow-up 12.30.7 months 59/60 (98.3)
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12-Month Event Free Survival (ITT/As-Treated)
P0.09 ITT
P0.01 As-Treated
Logrank test
Months post PCI
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Events From 6 to 12 Months

• DEB
• 2 Px with PCI in non-target vessel
• 1/66 (1.5) Px with re-re PCI in target lesion
• DES
• 2 Px with non-cardiac death
• 3/60 (5) Px with re-re PCI in target lesion

No new patient with MACE
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Summary PEPCAD II

• In the treatment of ISR the paclitaxel-eluting
  balloon catheter Sequent Please (B.Braun
  Melsungen AG)
• was safe and associated with a high procedural
  success rate,
• exhibited a significant reduction in 6-month late
  lumen loss and 6/12-month MACE when compared to
  the Taxus stent, and
• was not associated with late thrombosis in ?250
  patient years.

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The PEPCAD II Investigators

• F.X. Kleber, Unfallkrankenhaus Berlin
• H. Heuer, N. Schulze-Waltrup St. Johannes
  Hospital, Dortmund
• C. Vallbracht Herz- und Kreislaufzentrum,
  Rotenburg an der Fulda
• B. Scheller Universitätsklinikum des Saarlandes,
  Homburg/Saar
• C. Hengstenberg, Universitätsklinikum, Regensburg
• M. Leschke Städtische Kliniken, Esslingen
• C. Hamm, M. Rau Kerckhoff Klinik, Bad Nauheim
• G. Werner Städtisches Klinikum, Darmstadt
• D. Antoni Krankenhaus Bogenhausen, München
• W. Bocksch Charité Virchow, Berlin
• H.Ackermann Department for Biostatistics,
  University of Frankfurt/M
• M.Boxberger, B.Braun, Berlin
• R.Degenhardt, M.Unverdorben Clinical Research
  Institute, Rotenburg an der Fulda

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The PEPCAD ProgramPaclitaxel-Eluting
PTCA-Catheter in Coronary Artery Disease
Title Design Status PI
PEPCAD I SVD Sequent in 2.8mm, 120px, multi-center, GER 6mo-FU ? 12mo-FU? MU, CRI
PEPCAD II ISR Sequent vs Taxus in ISR, 131px, multi-center, GER 6mo-FU ? 12mo-FU? MU, CRI
PEPCAD III Sequent pre-loaded Coroflex Blue vs Cypher, 600 px, Europe Q2/07 recruiting B.SchellerC.Hamm
PEPCAD IV DM Sequent vs Taxus in DM, 160px, multi-center, Thailand, Malaysia Q2/07 recruiting D.Rosli, MU, CRI
PEPCAD V BIF Sequent, 25px, dual-center, GER Q3/ 07 recruiting D.Mathey F.Kleber MU, CRI
INDICOR Coroflex BlueSequent, Real World, 100px IRB U.Kaul, MU,CRI
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This is not the end. It is not even the beginning
of the end. But it is, perhaps, the end of the
beginning.
(Sir Winston S.Churchill)