Klinikum RosenheimDepartment of Diagnostic and Interventional Radiology

LIN

C 2

01

4

DEFINITIVE AR Severe Ca++ Arm 30-Day Results

Gunnar Tepe, MDOn behalf of Prof. Thomas Zeller and

the DEFINITIVE AR Investigators

Contributors•Co-Sponsors: Covidien and Bayer HealthCare (formerly MEDRAD)

•Principal Investigators: Prof. Thomas Zeller, MD & Prof. Gunnar Tepe, MD•Angiographic Core Lab: SynvaCor, Springfield, IL•Vascular Ultrasound Core Lab: Vascore, Boston, MA

•Sites: •Universitaets-Herzzentrum Freiburg - Bad Krozingen (Bad Krozingen)•Klinikum Rosenheim, Institut für Diagnostische und Interventionelle Radiologie•Medical Care Center Prof. Mathey, Prof. Schofer, Hamburg•Vascular Centre Berlin, Ev. Hospital Königin Elisabeth Herzberge gGmbH •Heart Center Leipzig•St. Franziskus-Hospital Münster•Imelda Hospital Bonheiden•Angiomed Krakow•Universitäts-Spital Zürich, Klinik für Angiologie•Medizinische Universitätsklinik III

Study Design

Yes

Registry arm for severely calcified lesions created to limit bail-out stenting (and therefore variables) in randomized arm.

* Directional Atherectomy + Anti-Restenotic Therapy

Purpose: Pilot study designed to assess and estimate the effect of treating a vessel with directional atherectomy + DCB (DAART)

compared to treatment with DCB alone

No

Devices

Covidien’sSilverHawk ™ & TurboHawk™

peripheral plaque excision systems

Bayer HealthCare’sPeripheral

Paclitaxel-coated angioplasty catheter with Paccocath® Technology

Study Design

• Study Design and Oversight– Prospective, randomized (DAART vs. DCB alone)

– 121 patients enrolled at 10 centers in Europe

– CEC, DSMB, and Steering Committee oversight

– Angiographic and Duplex Core Laboratory Analyses

• Primary Endpoint – Percent Stenosis at 1 Year

Study Design• Key Inclusion Criteria

– RCC 2-4– Target lesion 7-15 cm in length– RVD 4-7 mm– Baseline stenosis ≥ 70%

• Key Exclusion Criteria– In-stent restenosis– Aneurysmal target vessel– 2 or more lesions that require treatment in the target limb

• Follow-up assessments – Pre-discharge, 30 days, 6 months, and 1 year post-procedure

Baseline DemographicsDAART

Severe Ca++ Arm (N=19)

DAART (N= 48)

DCB (N = 54)

Age 69.7 ± 8.9 (19) 70.1 ± 9.7 69.0 ± 8.2

Male 73.7% (14/19) 64.6% 68.5%

History and Risk Factors

Angina 26.3% (5/19) 4.2% 9.3%

Diabetes 26.3% (5/19) 27.1% 35.2%

Hypertension 84.2% (16/19) 87.5% 81.5%

Hyperlipidemia 73.7% (14/19) 70.8% 68.5%

Renal Insufficiency 15.8% (3/19) 12.5% 14.8%

Current/Previous Smoker 36.8% (7/19) 50% 63%

Rutherford Category

2 15.8% (3/19) 27% 24%

3 84.2% (16/19) 70% 74%

4 0.0% (0/19) 2% 2%

Baseline Lesion CharacteristicsPer Core Lab Assessment

DAARTSevere Ca++ Arm

(N=19)

DAART(N= 48)

DCB (N = 54)

Lesion Length (cm) 11.9 10.6 9.7

Diameter Stenosis 88% 82% 85%

Reference vessel diameter (mm)

5.1 4.9 4.9

Minimum lumen diameter (mm)

0.7 1.0 0.8

Baseline Lesion CharacteristicsPer Core Lab Assessment

DAARTSevere Ca++

Arm (N=19)

DAART(N= 48)

DCB (N = 54)

Eccentric lesion 36.8% (7/19) 4.2% (2/48) 5.6% (3/54)

Ulcerated plaque 0.0% (0/19) 0.0% (0/48) 3.7% (2/54)

Calcification 94.7% (18/19) 70.8% (34/48) 74.1% (40/54)

Severe calcification* 89.5% (17/19) 25.0% (12/48) 18.5% (10/54)

TASC

A 31.6% (6/19) 33.3% (16/48) 48.1% (26/54)

B 42.1% (8/19) 56.3% (27/48) 42.6% (23/54)

C 26.3% (5/19) 10.4% (5/48) 9.3% (5/54)

D 0.0% (0/19) 0.0% (0/48) 0.0% (0/54)

*Defined as: dense circumferential calcification extending > 5 cm

Technical Success = 84.2%

•Defined as ≤ 30% residual stenosis following the protocol-defined treatment at the target lesion as determined by the Angiographic Core Laboratory.

DAARTSevere Ca++

DAART DCB P Value(DAART vs. DCB)

Technical Success 84.2% 89.6% 64.2% 0.004

Adjunctive Therapy (Post protocol-defined treatment)

DAARTSevere Ca++ DAART DCB

P Value(DAART vs. DCB)

Adjunctive Therapy

PTA (post-dil) 06.3%

(3/48)33.3% (18/54)

0.0011

Bail-out Stent5.3% (1/19)

0 3.7% (2/54) 0.4968

One bail-out stent placed in the DAART severe ca++ arm

Residual Stenosis = 24%Per Core Lab assessment

Contribution to Lumen GainPer Core Lab assessment

4.29 mm4.07 mm4.14 mmFinal Mean MLD=

Periprocedural Complications(Per CEC)

Severe Ca++ : DAART

DAART(N= 48)

DCB(N = 54)

P Value(DAART vs.

DCB)

Distal Embolization 5.3% (1/19) 6% (3/48) 0/54 0.101

No Intervention 1 1 0

Surgical Intervention 0 0 0

Endovascular Intervention 0 2 0

Dissection (flow-limiting, Grade C/D) 0% (0/19) 2% (1/48) 19% (10/54) 0.009

No Intervention 0 1 6

Surgical Intervention 0 0 0

Endovascular Intervention 0 0 4

Perforation 0% (0/19) 4% (2/48) 0/54 0.219

No Intervention 0 0 0

Surgical Intervention 0 0 0

Endovascular Intervention 0 2 0

Functional OutcomesSignificant improvement in ABI & WIQ scores at 30 days in all 3 cohorts

Mean ABI at Baseline and 30 Days

Percent of patients with Improvement in WIQ Scores at 30 days

Baseline 30 days Baseline 30 days

Conclusions• Acute results from the Severe Ca++ DAART Arm demonstrated high

technical success rate (84.2%) in complex calcified lesions with 1 bail-out stent placed and a low periprocedural complication rate

• Randomized Arm Acute results of DAART treatment show– Significantly higher technical success rate (DAART 89.6% vs. DCB 64.2%,

P=0.004) – Acceptable periprocedural complications– Significantly lower dissection rate (DAART 2% vs. DCB 19%, P = 0.009)

• Long-term data to determine the durability of DAART vs. DCB are necessary and forthcoming