A Prospective, Randomized Trial of a Paclitaxel coated Balloon vs. uncoated

Balloon Angioplasty in Patients with Drug-Eluting Stent Restenosis

PEPCAD-DES Study

Harald Rittger, MDUniversity of Erlangen;

Klinikum CoburgGermany

TCT 2011 – First Report Investigation

KLINIKUMCO B U R G

DisclosuresDisclosures

• Supported in part by an unrestricted grant by B.Braun, Melsungen, Germany

• Grant/Research Support• Consulting Fees/Honoraria• Major Stock Shareholder/Equity• Royalty Income• Ownership/Founder• Intellectual Property Rights• Other Financial Benefit

• B.Braun, Siemens• B.Braun, Siemens• none• none• None• None• none

Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

CentersCenters

Harald Rittger, MDKlinikum Coburg

Marc-A. Ohlow, MDZentralklinik Bad Berka

Andreas Brugger, MDKlinikum Kulmbach

Holger Thiele, MDHerzzentrum Leipzig

Ralf Birkemeyer, MDKlinikum Villingen-S.

Volker Kurowski, MDUniversität Lübeck

BackgroundBackground

• Drug-eluting stents (DES) significantly reduced the occurrence of restenosis and the subsequent need for repeat revascularization.

• Nevertheless, the incidence of DES-restenosis (DES-ISR) remains frequent due to the continuous increase in DES implantations.

BackgroundBackground

• Complex lesions with a high restenotic potential are sufficiently treated with present DES, limiting the use of bare-metal stents (BMS) to patients not eligible for dual antiplatelet therapy.

• Paclitaxel coated balloon angioplasty (SeQuent Please, B.Braun) has been shown to be superior to plain old balloon angioplasty (POBA) and non-inferior to paclitaxel eluting stent (PES) implantation for treatment of BMS restenosis.

BackgroundBackground

• Whether the use of paclitaxel coated balloon angioplasty is also effective in DES restenosis has not been sufficiently studied so far.

• We evaluated in a randomized, multicenter, single blinded trial the efficacy of paclitaxel coated balloon angioplasty (SeQuent Please, B.Braun, Germany) compared with plain old balloon angioplasty for DES restenosis in native coronary arteries.

Inclusion CriteriaInclusion Criteria• Age > 18 years

• Lesion in native coronary artery

• DES restenosis of Sirolimus eluting stents: Cypher, Yukon

Everolimus eluting stents: Xience, Promus

Paclitaxel eluting stents: Taxus

• Indication for PCI (symptoms, ischemia)

• Reference diameter 2.5 – 3.5 mm

• Lesion length ≤ 22 mm

Exclusion CriteriaExclusion Criteria

• thrombus within the target vessel• side branch ≥ 2 mm in diameter originating within the

restenosis or bifurcation lesion• multiple lesions in the target vessel• lesions in bypass grafts• total coronary artery occlusion• lesions within 1 mm of vessel origin or left main• planned surgery within 6 months after the index procedure• women with childbearing potential• contraindication or known hypersensitivity to acetylsalicylic

acid, clopidogrel, paclitaxel or heparin.

Primary EndpointPrimary Endpoint

• Primary endpoint: six-months late lumen loss at the target lesion.

• Superiority testing of the primary end point on an intention-to-treat basis.

Primary EndpointPrimary Endpoint

• With an assumed late lumen loss of 0.20±0.30mm in the drug coated balloon group and 0.80±0.80mm in the POBA group the necessary number of patients were 64 in the drug coated balloon and 34 in the POBA group to achieve 90% power

• With an assumed dropout rate of 10% the patient numbers to be recruited were 71 in the drug coated balloon and 38 in the POBA group.

Secondary EndpointsSecondary Endpoints

• Secondary angiographic endpoints Binary restenosis, minimal lumen diameter, percent diameter

stenosis (target lesion and total segment)

• Secondary clinical endpoints (definition according to ARC criteria)

Target lesion revascularization Myocardial infarction Death MACE as a composite of

• cardiac death, myocardial infarction attributable to target vessel, target lesion revascularization

110 patients enrolled andrandomized (2:1)

Paclitaxel coated balloon

N=72

Ballon angioplastyaloneN=38

6 months angiographic follow-up

88.9% (N=64/72)

6 months angiographic follow-up

81.6 % (N=31/38)

6-month clinical follow-up100 % (N=72/72)

6-month clinical follow-up100 % (N=38/38)

6 monthsASS+Clopidogrel

predilation

Baseline Characteristics

DCB POBA

Number of patients 72 38

Age (years) 69.8±10.8 * 64.0±11.3 Male 52 (72.2%) 26 (68.4%) Diabetes 26 (36.1%) 13 (34.2%) Hypertension 68 (94.4%) 36 (94.7%) Hyperlipidemia 59 (81.9%) 27 (71.1%) History of smoking 11 (15.3%) 6 (15.8%) BMI – kg/m2 28.1±4.1 27.2±3.5

* p=0.02

Baseline Angiography

DCB POBA

Lesion locationLAD 24 (33.3%) 16 (39.0%) CX 23 (32.0%)+ 3 (4.9%)RCA 25 (34.7%) 19 (46.3%)

QCARVD (mm) 2.29±0.51 2.30±0.52 MLD (mm) 0.66±0.40 0.62±0.44 % DS 72.1±14.5 74.0±16.2 Lesion length (mm) 11.2±6.5 12.2±8.2

+ p=0.005

DCB POBA

Pre-dilatation balloon

Length (mm) 16.0±6.0 16.1±5.5

Diameter (mm) 2.84±0.39 2.76±0.34

Inflation Time (sec) 39.4±26.3 41.9±16.9

Pressure (bar) 15.1±3.8 15.1±3.4

Procedural Data

DCB POBA

Study Balloon

Length (mm) 21.6±6.4* 18.9±6

Diameter (mm) 2.95±0.43 2.92±0.39

Inflation Time (sec) 57.6±16.0 53.2±17.3

Pressure (bar) 14.0±2.5 15.0±5.3

Procedural Data

* p=0.041

DCB POBA

RD (mm) 2.47±0.45 2.47±0.58

MLD (mm)Target lesion 2.15±0.42 2.14±0.53

Diameter stenosis (%)Target lesion 12.6±6.2 13.7±6.0

Post Procedure QCA

Primary Endpoint - Late Loss

POBA

1.03 ± 0.77

Primary Endpoint - Late Loss

POBA DCB

1.03 ± 0.770.43 ± 0.61

P < 0.001

P = 0.18 P < 0.001 P = <0.001 P < 0.001

Late Loss at 6 MonthsLate Loss at 6 MonthsPOBA DCB

DCB POBA P Value

Target lesion

MLD 1.75±0.70 1.10±0.73 < 0.001

% DS 29.6±24.3 51.1±31.0 < 0.001

Total segment

MLD 1.65±0.66 1.00±0.68 < 0.001

% DS 32.3±54.7 54.7±29.4 < 0.001

Follow-up QCA

P < 0.001 P < 0.001

Binary Angiographic Restenosis at 6 Binary Angiographic Restenosis at 6 MonthsMonths

Binary Restenosis

(%)

POBA DCB

DCB POBA P Value

Target lesion revascularization 11 (15.3 %) 14 (36.8 %) 0.005

Myocardial infarction

Non-target vessel 0 (0%) 0 (0%) --

Target vessel 0 (0 %) 1 (2.6 %) 0.345

Cardiac Death 1 (1.4%) 4 (10.5 %) 0.048

MACE * 12 (16.7 %) 19 (50.0 %) <0.001

Clinical Outcomes at 6 Months

*TLR, myocardial infarction attributable to target vessel, cardiac death

ConclusionConclusion• In this prospective, randomized, single-blind, multicenter

study the treatment strategy with paclitaxel coated balloon (SeQuent Please, B.Braun) compared with balloon angioplasty alone for treatment of DES restenosis showed:

– a significantly lower late loss (primary endpoint)

– a significantly lower binary restenosis rate, percent diameter stenosis and a significantly larger minimal lumen diameter at follow-up

– significantly less MACE

– no definite vessel thrombosis

A Prospective, Randomized Trial of a Paclitaxel coated Balloon vs. uncoated

Balloon Angioplasty in Patients with Restenosis of Drug-Eluting Stents

PEPCAD-DES Study

Harald Rittger, MDUniversity of Erlangen;

Klinikum CoburgGermany

TCT 2011 – First Report Investigation

KLINIKUMCO B U R G

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