m.unverdorben; acc march 2008 martin unverdorben rotenburg/fulda, germany and richmond, va, usa...

M.Unverdorben; ACC March 2008

Martin UnverdorbenRotenburg/Fulda, Germany and Richmond, VA, USA Clinical Research Institute, Center for Cardiovascular

Diseases

On behalf of the PEPCAD II Investigators

The Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary

Artery Disease

PEPCAD II-ISR

M.Unverdorben; ACC March 2008 2

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


AgendaAgendaThe PACCOCATH technology

PEPCAD II ISR 6-month angiographic and clinical follow-up

PEPCAD II ISR 12-month clinical follow-up

Descriptive statistics: Mean ± SD Inferential statistics: Student’s t-test, Fisher’s

exact test, Logrank test Level of significance: p < 0.05

StatisticsStatistics


Scheller Heart 2007, 93: 539-41

DES vs. DEB (PACCOCATH)DES vs. DEB (PACCOCATH)

Hwang, Circulation 2001; 104: 600-5

Instant and short term drug release from balloon

~ 300 - 600 µg PaclitaxelNo polymersStenting optional

Slow and continuous drug release from stent struts

~100 - 200 µg Paclitaxel Sirolimus

Polymers with associated reactions

Implies stent deployment

DES

DEB

Creel, Circ Res 2000; 86: 879-884

ex vivo perfusion of calf carotid ex vivo perfusion of calf carotid arteries,transmural distributionarteries,transmural distribution


The Matrix CoatingThe Matrix CoatingPACCOCATH technology creates a unique matrix

coatingpure

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


*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

SeQuent® (uncoated balloon)

SeQuent® Please* (coated balloon)


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


Primary Variable

6-month late lumen loss

Secondary Variables

Procedural success (≤30%)6-month binary restenosis rate6-month MACEMACE at 1 and 3 years


Inclusion Criteria

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

Medication

ASS ≥ 100 mg dailyClopidogrel 75 mg daily

–3 months DEB

–6 months DES


Patients (ITT: N=131) DEB (N=66) DES (N=65) pAge [years] 64.6±9.7 65.1±8.7 0.7Male 48 (72.7%) 50 (76.9%) 0.7 BMI [kg/m2] 27.9 ± 4.6 28.6±4.2 0.4Serum cholesterol [mg/dl] 172 ± 42 180 ± 34 0.3Serum LDL [mg/dl] 93 ± 39 98 ± 29 0.4Diabetes mellitus 22 (33.3%) 17 (26.2%) 0.4Current/ex-smokers 44 (66.7%) 36 (55.4%) 0.3

Hypertension 53 (80.3%) 54 (83.1%) 0.8Family history of CAD 21 (31.8%) 22 (33.8%) 0.9Previous MI 37 (56.1%) 28 (43.1%) 0.2PAVD 9 (13.6%) 7 (10.8%) 0.8Serum crea [mg/dL] 1.1 ± 1 1.0 ± 0.2 0.4


Baseline Angiography (ITT: N=131)DEB (N=66) DES (N=65) p

1-vessel disease [%]

28.8 35.4


40.9 35.4 0.7


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 <0.0001

Stenosis post PCI [%]

20 10 11 8 <0.001


Outcome (ITT: N=131)DEB (N=66) DES (N=65) 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


As-TreatedRandomization

N=131

Sequent Pleasen=66

Taxusn=65

4 protocol violators

Lesion too long (41.1mm)Multilesion PCI in metal

jacketSignificant flap after PCI

Severe renal failure

1 crossing failure treat/w convent balloon

4 crossing failure treat/w Sequent Please

60 DES2 with additional DES

66 DEB56 DEB only6 DEB + BMS4 DEB (cross-

over)


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%) 0.02Myocardial 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


Event Free Survival (ITT/As-Treated)

70

75

80

85

90

95

100

0 2 4 6 8 10

Sub

ject

s [%

]

DES/ I TT DEB/ I TT

DES/AsT DEB/AsT

*p=0.2ITT

*p=0.03As-Treated

Months post PCI *Logrank test


12-Month Follow-up: As-Treated

60 DES2 with additional

DES

66 DEB56 DEB only6 DEB + BMS4 DEB (cross-

over)

Unknown today

2/60 (3.3%)

Lost to FU1/60 (1.7%)

Follow-up12.3±0.8 months

57/60 (95.0%)

Deaths3/60 (5%)

Unknown today

1/66 (1.5%)

Lost to FU0/60 (0%)

Follow-up12.3±0.7 months

59/60 (98.3%)

Deaths2/66 (3.0%)


12-Month Event Free Survival (ITT/As-Treated)

70

75

80

85

90

95

100

0 5 10 15

Sub

ject

s [%

]

DES/ I TT DEB/ I TT

DES/AsT DEB/AsT

P*=0.09ITT

P*=0.01As-Treated

Months post PCI *Logrank test


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


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.


The PEPCAD II InvestigatorsF.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, MünchenW. Bocksch; Charité Virchow, Berlin

H.Ackermann; Department for Biostatistics, University of Frankfurt/M

M.Boxberger, B.Braun, BerlinR.Degenhardt, M.Unverdorben; Clinical Research Institute,

Rotenburg an der Fulda


The PEPCAD ProgramPaclitaxel-Eluting PTCA-Catheter in Coronary Artery

Disease Title Design Status PIPEPCAD 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

Blue+Sequent, Real World, 100px

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 martin unverdorben rotenburg/fulda, germany and richmond, va, usa...

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