DEFINITIVE AR - Acute Outcomes - Directional AthErectomy Followed by a PaclItaxel-Coated BallooN to InhibiT RestenosIs and maintain Vessel PatEncy: A Pilot Study of Anti-Restenosis Treatment Prof. Thomas Zeller, M.D. Universitaets-Herzzentrum Freiburg - Bad Krozingen Bad Krozingen, Germany

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 SC1206092013A

Study Design DAART* DCB 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 General and Angiographic Criteria Assessment Lesion severely calcified? Guidewire passage, enrollment & Randomization DAART* (N = 48) DCB (N = 54) Guidewire Passage & Enrollment (N=19) No Yes Yes Severe Calcification: Dense circumferential calcification and calcification extending more than five (5) continuous centimeters of length prior to contrast injection or digital subtraction angiography There was 6 month lag in ca++ arm due to prolonged enrollment period. Acute results from the ca++ arm will be presented soon. The sample size difference between groups is attributed to the blocked randomized trial design. Registry arm for severely calcified lesions created to limit bail-out stenting (and therefore variables) in randomized arm. * Directional Atherectomy + Anti-Restenotic Therapy SC1206092013A

Devices Bayer HealthCare’s Covidien’s Peripheral SilverHawk ™ & TurboHawk™ peripheral plaque excision systems Bayer HealthCare’s Peripheral Paclitaxel-coated angioplasty catheter with Paccocath® Technology SC1206092013A

Study Design Study Design and Oversight Primary Endpoint 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 SC1206092013A

Study Design Key Inclusion Criteria Key Exclusion 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 SC1206092013A

Baseline Demographics DAART (N= 48) DCB (N = 54) P Value* Age 70.1 ± 9.7 69.0 ± 8.2 0.4383 Male 64.6% 68.5% 0.6807 History and Risk Factors Angina 4.2% 9.3% 0.4425 Diabetes 27.1% 35.2% 0.4014 Hypertension 87.5% 81.5% 0.4300 Hyperlipidemia 70.8% 0.8323 Renal Insufficiency 12.5% 14.8% 0.7807 Current/Previous Smoker 50.0% 63.0% 0.3076 Rutherford Clinical Category 0.9096 2 24.0% 3 74.1% 4 2.1% 1.9% *No significant differences between groups SC1206092013A

Baseline Lesion Characteristics Per Core Lab Assessment DAART (N= 48) DCB (N = 54) P Value* Lesion Length (cm) 10.6 9.7 0.3034 Diameter Stenosis 82% 85% 0.3468 Reference vessel diameter (mm) 4.9 0.4794 Minimum lumen diameter (mm) 1.0 0.8 0.3372 Calcification 70.8% 74.1% 0.4758 *No significant differences between groups SC1206092013A

Technical Success Defined as ≤ 30% residual stenosis following the protocol-defined treatment at the target lesion as determined by the Angiographic Core Laboratory. DAART DCB P Value Technical Success 89.6% 64.2% 0.004 SC1206092013A

Minimum Lumen Diameters DAART resulted in a significantly larger minimum lumen diameter (MLD) following the protocol-defined treatment (4.27 mm vs. 3.78 mm, P = 0.045) P = 0.045 MLD = 4.27 mm MLD = 3.78 mm Min. Lumen Diameter (mm) This slide shows the mean MLD at baseline and following each step of the protocol-defined procedure. DAART Arm: 8 lesions were pre-dialated DCB arm: 40 lesions were pre-dialated SC1206092013A

Adjunctive Therapy (Post protocol-defined treatment) DAART (N= 48) DCB (N = 54) P Value Adjunctive Therapy PTA (post-dil) 6.3% (3/48) 33.3% (18/54) 0.0011 Bail-out Stent 3.7% (2/54) 0.4968 The bail out stenting rate in this trial is considerably lower than the DCB studies published to date Significantly higher rate of PTA following treatment with DCB in DCB arm SC1206092013A

Residual Stenosis Residual diameter stenosis was significantly lower in the DAART arm P = 0.0002 P = 0.0256 SC1206092013A

Periprocedural Complications (Per CEC) DAART (N= 48) DCB (N = 54) p-value Distal Embolization 6% (3/48) 0/54 0.101 No Intervention 1 Surgical Intervention Endovascular Intervention 2 Dissection (flow-limiting, Grade C/D) 2% (1/48) 19% (10/54) 0.009 6 4 Perforation 4% (2/48) 0.219 SC1206092013A

Functional Outcomes Significant improvement in ABI & WIQ scores at 30 days in both cohorts Mean ABI at Baseline and 30 Days Percent of patients with Improvement in WIQ Scores at 30 days P < 0.0001 P < 0.0001 No significant differences between groups No significant differences between groups at baseline or at 30- days Baseline 30 days Baseline 30 days SC1206092013A

Conclusions 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 SC1206092013A