1. 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, MD University of Erlangen; Klinikum Coburg Germany TCT 2011 – First Report Investigation KLINIKUM CO B U R G

2. Disclosures 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 none None none Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany

3. Centers Harald Rittger, MD Klinikum Coburg Marc-A. Ohlow, MD Zentralklinik Bad Berka Andreas Brugger, MD Klinikum Kulmbach Holger Thiele, MD Herzzentrum Leipzig Ralf Birkemeyer, MD Klinikum Villingen-S. Volker Kurowski, MD Universität Lübeck

4. Background 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.

5. Background 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.

6. Background 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.

7. Inclusion 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

8. Exclusion 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.

9. Primary 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.

10. Primary 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.

11. Secondary 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

12. 110 patients enrolled and randomized (2:1) 110 patients enrolled and randomized (2:1) Paclitaxel coated balloon N=72 Paclitaxel coated balloon N=72 Ballon angioplasty alone N=38 Ballon angioplasty alone N=38 6 months angiographic follow-up 88.9% (N=64/72) 6 months angiographic follow-up 88.9% (N=64/72) 6 months angiographic follow-up 81.6 % (N=31/38) 6 months angiographic follow-up 81.6 % (N=31/38) 6-month clinical follow-up 100 % (N=72/72) 6-month clinical follow-up 100 % (N=72/72) 6-month clinical follow-up 100 % (N=38/38) 6-month clinical follow-up 100 % (N=38/38) 6 months ASS+Clopidogrel predilation

13. Baseline Characteristics DCBPOBA Number of patients7238 Age (years)69.8±10.8 *64.0±11.3 Male52 (72.2%)26 (68.4%) Diabetes26 (36.1%)13 (34.2%) Hypertension68 (94.4%)36 (94.7%) Hyperlipidemia59 (81.9%)27 (71.1%) History of smoking11 (15.3%)6 (15.8%) BMI – kg/m 2 28.1±4.127.2±3.5 * p=0.02

14. Baseline Angiography DCBPOBA Lesion location LAD24 (33.3%)16 (39.0%) CX23 (32.0%)+3 (4.9%) RCA25 (34.7%)19 (46.3%) QCA RVD (mm)2.29±0.512.30±0.52 MLD (mm)0.66±0.400.62±0.44 % DS72.1±14.574.0±16.2 Lesion length (mm) 11.2±6.512.2±8.2 + p=0.005

15. DCBPOBA Pre-dilatation balloon Length (mm)16.0±6.016.1±5.5 Diameter (mm)2.84±0.392.76±0.34 Inflation Time (sec)39.4±26.341.9±16.9 Pressure (bar)15.1±3.815.1±3.4 Procedural Data

16. DCBPOBA Study Balloon Length (mm)21.6±6.4*18.9±6 Diameter (mm)2.95±0.432.92±0.39 Inflation Time (sec)57.6±16.053.2±17.3 Pressure (bar)14.0±2.515.0±5.3 Procedural Data * p=0.041

17. DCBPOBA RD (mm) 2.47±0.452.47±0.58 MLD (mm) Target lesion2.15±0.422.14±0.53 Diameter stenosis (%) Target lesion12.6±6.213.7±6.0 Post Procedure QCA

18. Primary Endpoint - Late Loss POBA 1.03 ± 0.77

19. Primary Endpoint - Late Loss POBADCB 1.03 ± 0.77 0.43 ± 0.61 P < 0.001

20. P = 0.18 P < 0.001 P = <0.001 P < 0.001 Late Loss at 6 Months POBADCB

21. POBAP Value Target lesion MLD1.75±0.701.10±0.73< 0.001 % DS29.6±24.351.1±31.0< 0.001 Total segment MLD1.65±0.661.00±0.68< 0.001 % DS32.3±54.754.7±29.4< 0.001 Follow-up QCA

22. P < 0.001 Binary Angiographic Restenosis at 6 Months Binary Restenosis (%) POBADCB

23. POBAP Value Target lesion revascularization 11 (15.3 %)14 (36.8 %)0.005 Myocardial infarction Non-target vessel0 (0%) -- Target vessel0 (0 %)1 (2.6 %)0.345 Cardiac Death1 (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

24. Conclusion 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

25. 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, MD University of Erlangen; Klinikum Coburg Germany TCT 2011 – First Report Investigation KLINIKUM CO B U R G Thank you very much for your attention! for your attention!