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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
M.Unverdorben; ACC March 2008
Presenter Disclosure Information
PEPCAD II 12-Month Follow-up
The following relationships exist related to this presentation:
M.Unverdorben
Nothing to disclose
B.Scheller
Consulting and lecture fees from BBraun, co-patent owner of
Sequent® Please
M.Unverdorben; ACC March 2008
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: Student’s t-test, Fisher’s
exact test, Logrank test
 Level of significance: p < 0.05
M.Unverdorben; ACC March 2008
DES vs. DEB (PACCOCATH)
DES
DEB
Scheller Heart 2007, 93: 539-41
Slow and continuous drug
release from stent struts
~100 - 200 µg Paclitaxel
ex vivo perfusion of calf carotid
Sirolimus
arteries,transmural
distribution
Polymers with associated
reactions
Hwang, Circulation 2001; 104: 600-5 Implies stent deployment
Instant and short term drug
release from balloon
~ 300 - 600 µg Paclitaxel
No polymers
Stenting optional
Creel, Circ Res 2000; 86: 879-884
M.Unverdorben; ACC March 2008
The Matrix Coating
PACCOCATH technology creates a unique matrix coating
pure paclitaxel
without
paclitaxel + hydrophilic spacer
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
M.Unverdorben; ACC March 2008
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
M.Unverdorben; ACC March 2008
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
M.Unverdorben; ACC March 2008
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
M.Unverdorben; ACC March 2008
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
M.Unverdorben; ACC March 2008
Patients (ITT: N=131)
DEB (N=66)
 Age [years]
64.6±9.7
 Male
48 (72.7%)
 BMI [kg/m2]
27.9 ± 4.6
 Serum cholesterol [mg/dl] 172 ± 42
 Serum LDL [mg/dl]
93 ± 39
 Diabetes mellitus
22 (33.3%)
 Current/ex-smokers
44 (66.7%)
 Hypertension
53 (80.3%)
 Family history of CAD
21 (31.8%)
 Previous MI
37 (56.1%)
 PAVD
9 (13.6%)
 Serum crea [mg/dL]
1.1 ± 1
M.Unverdorben; ACC March 2008
DES (N=65)
65.1±8.7
50 (76.9%)
28.6±4.2
180 ± 34
98 ± 29
17 (26.2%)
36 (55.4%)
54 (83.1%)
22 (33.8%)
28 (43.1%)
7 (10.8%)
1.0 ± 0.2
p
0.7
0.7
0.4
0.3
0.4
0.4
0.3
0.8
0.9
0.2
0.8
0.4
Baseline Angiography (ITT: N=131)
DEB (N=66)
DES (N=65)
1-vessel disease [%]
28.8
35.4
2-vessel disease [%]
40.9
35.4
3-vessel disease [%]
30.3
29.2
Stenosis length [mm]
15.7  6.6
15.4  6.6
Mehran I
31 (47.0%)
25 (38.5%)
Mehran II
20 (30.3%)
26 (40.0%)
Mehran III
14 (21.2%)
12 (18.5%)
Mehran IV
MLD pre PCI [mm]
Stenosis pre PCI [%]
MLD post PCI [mm]
Stenosis post PCI [%]
1 ( 1.5%)
p
0.7
0.8
0.7
2 ( 3.1%)
0.74  0.27
0.77  0.30
0.6
74  9
73  9
0.5
2.30  0.40
2.56  0.41
<0.0001
20  10
11  8
<0.001
M.Unverdorben; ACC March 2008
Outcome (ITT: N=131)
DEB (N=66)
DES (N=65)
p
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
Follow-up: clinical [months]
Death
Total MACE
*2/64 (3.1%)
5/64 (7.8%)
(w/o noncardiac death)
*1 each: non-cardiac & cardiac but
not lesion related
** non-cardiac death
M.Unverdorben; ACC March 2008
(1.5%)
1
**1/65 (1.5%)
1
11/65 (16.9%)
fNSTEMI
0.2
due to side
branch occlusion
As-Treated
Randomization
N=131
Sequent Please
n=66
Taxus
n=65
4 protocol violators
Lesion too long (41.1mm)
Multilesion PCI in metal jacket
Significant flap after PCI
Severe renal failure
66 DEB
4 crossing
failure treat/w
Sequent Please
56 DEB only
6 DEB + BMS
4 DEB (cross-over)
M.Unverdorben; ACC March 2008
1 crossing
failure treat/w
convent balloon
60 DES
2 with additional DES
Outcome (AsT: N=126)
DEB (N=66)
DES (N=60)
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%)
Death
Total MACE
*2/64 (3.1%)
(w/o noncardiac death)
3/64 (4.7%)
*1 cardiac, not lesion related 2 non cardiac
** non-cardiac death
M.Unverdorben; ACC March
f1/60
(1.7%)
1
**1/60 (1.7%)
1
11/60 (18.3%)
fNSTEMI
2008
occlusion
0.02
due to side branch
Event Free Survival (ITT/As-Treated)
100
Subjects [%]
95
90
*p=0.2
ITT
85
80
75
70
0
DES/ITT
DEB/ITT
DES/AsT
DEB/AsT
2
4
*p=0.03
As-Treated
6
Months post PCI
M.Unverdorben; ACC March 2008
8
*Logrank test
10
12-Month Follow-up: As-Treated
66 DEB
56 DEB only
6 DEB + BMS
4 DEB (cross-over)
Unknown today
1/66 (1.5%)
Lost to FU
0/60 (0%)
Deaths
2/66 (3.0%)
60 DES
2 with additional DES
Unknown today
2/60 (3.3%)
Lost to FU
1/60 (1.7%)
Deaths
3/60 (5%)
Follow-up
12.3±0.7 months
59/60 (98.3%)
Follow-up
12.3±0.8 months
57/60 (95.0%)
M.Unverdorben; ACC March 2008
12-Month Event Free Survival
(ITT/As-Treated)
100
Subjects [%]
95
90
P*=0.09
ITT
85
80
75
70
0
DES/ITT
DEB/ITT
DES/AsT
DEB/AsT
5
Months post PCI
M.Unverdorben; ACC March 2008
P*=0.01
As-Treated
10
*Logrank test
15
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
M.Unverdorben; ACC March 2008
Summary PEPCAD II
In the treatment of ISR the paclitaxeleluting 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.
M.Unverdorben; ACC March 2008
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
M.Unverdorben; ACC March 2008
The PEPCAD Program
Paclitaxel-Eluting PTCA-Catheter in Coronary Artery Disease
Title
Design
Status
PI
PEPCAD I SVD Sequent in ≤2.8mm,
6mo-FU  MU, CRI
120px, multi-center, GER 12mo-FU
PEPCAD II
ISR
Sequent vs Taxus in ISR, 6mo-FU  MU, CRI
131px, multi-center, GER 12mo-FU
PEPCAD III
Sequent + pre-loaded
Coroflex Blue vs Cypher,
600 px, Europe
Sequent vs Taxus in DM,
160px, multi-center,
Thailand, Malaysia
Sequent, 25px, dualcenter, GER
PEPCAD IV DM
PEPCAD V BIF
INDICOR
Coroflex Blue+Sequent,
Real World,
100px
M.Unverdorben; ACC March 2008
Q2/07
B.Scheller
recruiting C.Hamm
Q2/07
recruiting
D.Rosli,
MU, CRI
Q3/ 07
D.Mathey
recruiting F.Kleber
MU, CRI
IRB
U.Kaul,
MU,CRI
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)
M.Unverdorben; ACC March 2008