Klinikum Rosenheim Department of Diagnostic and Interventional Radiology LINC 2014 DEFINITIVE AR Severe Ca++ Arm 30-Day Results Gunnar Tepe, MD On 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 General and Angiographic Criteria Assessment Lesion severely calcified? Guidewire passage, enrollment & Randomization DAART* (N = 48) DCB (N = 54) Guidewire Passage & Enrollment DAART* (N=19) 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’s SilverHawk ™ & TurboHawk™ peripheral plaque excision systems Bayer HealthCare’s Peripheral 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 Demographics DAART Severe Ca++ Arm (N=19) DAART (N= 48) DCB (N = 54) Age69.7 ± 8.9 (19) 70.1 ± ± 8.2 Male73.7% (14/19) 64.6%68.5% History and Risk Factors Angina26.3% (5/19) 4.2%9.3% Diabetes26.3% (5/19) 27.1%35.2% Hypertension84.2% (16/19) 87.5%81.5% Hyperlipidemia73.7% (14/19) 70.8%68.5% Renal Insufficiency15.8% (3/19) 12.5%14.8% Current/Previous Smoker36.8% (7/19)50%63% Rutherford Category % (3/19) 27%24% % (16/19) 70%74% 4 0.0% (0/19) 2%

Baseline Lesion Characteristics Per Core Lab Assessment DAART Severe Ca++ Arm (N=19) DAART (N= 48) DCB (N = 54) Lesion Length (cm) Diameter Stenosis88% 82%85% Reference vessel diameter (mm) Minimum lumen diameter (mm)

Baseline Lesion Characteristics Per Core Lab Assessment DAART Severe Ca++ Arm (N=19) DAART (N= 48) DCB (N = 54) Eccentric lesion36.8% (7/19)4.2% (2/48)5.6% (3/54) Ulcerated plaque0.0% (0/19)0.0% (0/48)3.7% (2/54) Calcification94.7% (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 A31.6% (6/19)33.3% (16/48)48.1% (26/54) B42.1% (8/19)56.3% (27/48)42.6% (23/54) C26.3% (5/19)10.4% (5/48)9.3% (5/54) D0.0% (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. DAART Severe Ca ++ DAARTDCBP Value (DAART vs. DCB) Technical Success84.2% 89.6%64.2%0.004

Adjunctive Therapy (Post protocol-defined treatment) DAART Severe Ca ++ DAARTDCB P Value (DAART vs. DCB ) Adjunctive Therapy PTA (post-dil)0 6.3% (3/48) 33.3% (18/54) Bail-out Stent 5.3% (1/19) 03.7% (2/54) One bail-out stent placed in the DAART severe ca++ arm

Residual Stenosis = 24% Per Core Lab assessment

Contribution to Lumen Gain Per Core Lab assessment 4.29 mm 4.07 mm 4.14 mm Final 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/ No Intervention 110 Surgical Intervention 000 Endovascular Intervention 020 Dissection (flow-limiting, Grade C/D) 0% (0/19)2% (1/48)19% (10/54)0.009 No Intervention 016 Surgical Intervention 000 Endovascular Intervention 004 Perforation 0% (0/19)4% (2/48)0/ No Intervention 000 Surgical Intervention 000 Endovascular Intervention 020

Functional Outcomes Significant 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

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