DES in the SFA Will it ever work

DES in the SFA: Will it ever work? Lewis B. Schwartz, M. D. , F. A. C. S. Abbott Laboratories

Clinical efficacy of sirolimus and paclitaxel Sirolimus-eluting Paclitaxel-eluting Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice M-C, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus and paclitaxel-eluting coronary stents. New Engl J Med 2007; 356: 998 -1008.

Infrapopliteal DES – Clinical Studies Study n Lesion length (cm) Treatment Group Restenosis after 6 -mos. Siablis, 2005, 2007 29 1. 3 Various (historical) 55% (79% @1 -year) 29 1. 4 Cypher 4. 0% (37% @ 1 -year) Commeau, 2006 30 NR Cypher NR 30 NR Bx Velocity 39% 30 NR Cypher 0% Siablis, 2007 29 2. 6 Taxus 18% (77% @ 1 -year) Rosales, 2008 24 NR Cypher (35)/Taxus (6) 10% (mean F/U of 9 mos. ) Scheinert, 2006 Siablis D, Kraniotis P, Karnabatidis D, et al. Sirolimus-eluting versus bare stents for bailout after suboptimal infrapopliteal angioplasty for critical limb ischemia. J. Endovasc. Ther. 2005; 12: 685 -695. Siablis D, Karnabatidis K, Katsanos K, et al. Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: Enduring 1 -year angiographic and clinical benefit. J. Endovasc. Ther. 2007; 14: 241 -250. Commeau P, Barragan P, Roquebert PO. Sirolimus for below the knee lesions: Mid-term results of the Siro. BTK study. Cath. Cardiovasc. Interv. 2006; 68: 793 -796. Scheinert D, Ulrich M, Scheinert S, et al. Comparison of sirolimus-eluting vs. bare-metal stents for the treatment of infrapopliteal obstructions. Euro. Interv. 2006; 2: 169 -174. Siablis D, Karnabatidis D, Katsanos K, et al. Infrapopliteal application of paclitaxel-eluting stents for critical limb ischemia: midterm angiographic and clinical results. J. Vasc. Interv. Radiol. 2007; 18: 1351 -1361. Rosales OR, Mathewkutty S, Gnaim C. Drug-eluting stent for belowthe-knee lesions in patients with critical limb ischemia: Long-term follow-up. Cath. Cardiovasc. Interv. 2008; 72: 112 -115.

Bosiers M, Deloose K, Peeters P. DES vs. BMS to treat BTK lesions: the DESTINY trial. Paper presented at: Veith Vascular Conference, 2009; New York, New York.

Bosiers M, Deloose K, Peeters P. DES vs. BMS to treat BTK lesions: the DESTINY trial. Paper presented at: Veith Vascular Conference, 2009; New York, New York.

Restenosis in the SFA Post-procedure 9 -mos.

Peripheral DES Clinical Trial Acronym Device Drug and dose Polymer and duration of elution SIROCCO Sirolimuseluting S. M. A. R. T. Sirolimus 90 µg/cm 2 “elastic copolymer” ( 7 days) STRIDES Dynalink-E Everolimus 225 µg/cm 2 EVAL ( 90 days) ZILVER PTX Zilver PTX Paclitaxel 300 µg/cm 2 None (immediate) Photo Minar E. DES for SFA and Peripheral Arteries. Paper presented at: Cardiovascular Revascularization Therapeutics, 2007; Washington, D. C. 008; 72: 112 -115. Duda SH, Pusich B, Richter G, Landwehr P, Oliva VL, Tielbeek A, Wiesinger B, Hak JB, Tielemans H, Ziemer G, Cristea E, Lansky A, Beregi JP. Sirolimus-eluting stents for the treatment of obstructive superficial femoral artery disease: Six-months results. Circ. 2002; 106: 1505 -1509. Dake MD. Are all drugs equal and do we need polymers? Paper presented at: Cardiovascular and Interventional Radiological Society of Europe; September 15, 2008; Copenhagen, Denmark.

Clinical Rates of Stent Fracture in the SFA Duda SH, et al. Circ. 2002; 106: 1505 -1509. Schillinger M, et al. New Engl. J. Med. 2006; 354: 1879 -1888. Schlager O, et al. J. Endovasc. Ther. 2005; 12: 676 -684. Krankenberg H, et al. Circ. 2007; 116: 285 -292. Katzen BT. Transcatheter Cardiovascular Therapeutics, Washington, 2007. Scheinert D. Leipzig Interventional Course, Leipzig, 2008. Ferreira M, et al. Eur. J. Vasc. Endovasc. Surg. 2007; 34: 702 -708. Schroë H, et al. CIRSE, 2006; Duda S. Leipzig Interventional Course. Leipzig, Germany, 2009. CIRSE 2009, Lisbon, Portugal

Peripheral DES Elution (experimental) Dynalink-E 8 x 28 mm stents in porcine iliac arteries (n=8 stents in 2 animals per time point); XIENCE V 3 x 12 mm stents in porcine coronary arteries (n=6 stents in 2 animals per time point); data represent mean SD SIROCCO data from Donohoe D. Cordis Drug-Eluting Stent Evolution. Cordis, a Johnson & Johnson Company, 2004. ZILVER PTX data from Heldman AW, Ragheb AO. Paclitaxel persists in vessel wall after rapid delivery from nonpolymeric paclitaxel coating on selfexpanding Nitinol stents (abstract). Am. J. Cardiol. 2004; 94 (suppl 6 A): 27 E. Data on file at Abbott Laboratories. The Dynalink device is cleared by the U. S. Food & Drug Administration (FDA) for biliary tract implantation only as the safety and efficacy for its use in the vascular system has not been established.

The SIROCCO Studies Duda SH, Pusich B, Richter G, Landwehr P, Oliva VL, Tielbeek A, Wiesinger B, Hak JB, Tielemans H, Ziemer G, Cristea E, Lansky A, Beregi JP. Sirolimus-eluting stents for the treatment of obstructive superficial femoral artery disease: Six-months results. Circ. 2002; 106: 1505 -1509. Duda SH, Bosiers M, Lammer J, Scheinert D, Zeller T, Tielbeek A, Anderson J, Wiesinger B, Tepe G, Lansky A, Mudde C, Tielemans H, Bérégi JP. Sirolimus-eluting versus bare Nitinol stent for obstructive superficial femoral artery disease: The SIROCCO II Trial. J. Vasc. Interv. Radiol. 2005; 16: 331338.

SIROCCO II long-term results Duda S. SIROCCO II: Long-term results of stenting TASC C lesions in the SFA. Euro. PCR, Barcelona, Spain, 2007. Duda SH, Bosiers M, Lammer J, Scheinert D, Zeller T, Oliva V, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J. Endovasc. Ther. 2006; 13: 701 -710.

Six and Twelve Months STRIDES results A First-in-Man Evaluation of DYNALINK–E in the SFA Johannes Lammer 1, Martin Schillinger 1, Thomas Zeller 2 , Els Boone 3, Margo J. Zaugg 3 and Lewis B. Schwartz 3 on behalf of STRIDES Investigators. 1 Medical University Vienna, Austria, 2 Herzzentrum Bad Krozingen, Germany, 3 Abbott Vascular, USA

Demographics N = 104 Age (mean ± SD, range) 69 ± 8. 9 yr (49 -85) Male 57% Diabetes 39% Current smoker 37% Hypercholesterolemia 57% Hypertension 78% Coronary artery disease 42% Cerebrovascular disease 18% Prior ipsilateral lower extremity intervention 19% Contralateral PVD 60% CIRSE 2009, Lisbon, Portugal

Indications N = 104 Intermittend claudication 83% Critical limb ischemia 17% Rutherford Becker Classification II (moderate claudication) 34% III (severe claudication) 49% IV (ischemic rest pain) 8. 7% V (ischemic tissue loss) 8. 7% ABI, mean ± SD (n) CIRSE 2009, Lisbon, Portugal 0. 6 ± 0. 2 (95)

Lesion Characteristics N = 106 Lesion origin De novo 91% Restenotic 9. 4% Calcification Moderate 51% Severe 27% Total occlusion 45% Patent run off vessels One 26% Two 27% Three 47% Lesion Length, mean ± SD *106 lesions in 104 patients CIRSE 2009, Lisbon, Portugal 9. 0 ± 4. 3 cm

Rutherford Becker (RB) Clinical Category Sustained clinical benefit in 80% of the patients at 12 months CIRSE 2009, Lisbon, Portugal

Limb Salvage – CLI vs. Claudicants (n=86) CLI Pts (n=18) P=0. 0017 Days post index procedure 0 (0, 30] (30, 180] (180, 365] (365, 393] 18 0 0 100% 18 0 1 94. 4% 17 0 0 94. 4% 17 0 1 88. 9% 16 16 0 88. 9% 86 0 0 100% 86 86 0 100% CLI Patients # at Risk # Censored # Events % Event Free Claudicants # at Risk # Censored # Events % Event Free CIRSE 2009, Lisbon, Portugal

VIENNA Absolute and STRIDES Primary Patency 100% Primary Patency 75% VIENNA (stent) 50% STRIDES 25% VIENNA (PTA) 0% 0 40 80 120 160 200 240 280 320 360 400 Days Post Index Procedure Schillinger M, Sabeti S, Loewe C et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. New Engl. J. Med. 2006; 354: 1879 -18881 CIRSE 2009, Lisbon, Portugal

Dake MD. Interim analysis of two-year clinical results for the Zilver® PTX® drug-eluting peripheral stent. Paper presented at: Cardiovascular Interventional Society of Europe, 2009; Lisbon, Portugal.

Dake MD. Interim report on the Zilver PTX clinical trial. International Society of Endovascular Therapy (ISET), Hollywood, FL, 2007.

Dake MD. Interim report on the Zilver PTX clinical trial. International Society of Endovascular Therapy (ISET), Hollywood, FL, 2007.

Dake MD. Interim analysis of two-year clinical results for the Zilver® PTX® drug-eluting peripheral stent. Paper presented at: Cardiovascular Interventional Society of Europe, 2009; Lisbon, Portugal.

Peripheral DES Clinical Trial Acronym Device Drug and dose Polymer and duration of elution SIROCCO Sirolimuseluting S. M. A. R. T. Sirolimus 90 µg/cm 2 “elastic copolymer” ( 7 days) STRIDES Dynalink-E Everolimus 225 µg/cm 2 EVAL ( 90 days) ZILVER PTX Zilver PTX Paclitaxel 300 µg/cm 2 None (immediate) Photo Minar E. DES for SFA and Peripheral Arteries. Paper presented at: Cardiovascular Revascularization Therapeutics, 2007; Washington, D. C. Duda SH, Pusich B, Richter G, Landwehr P, Oliva VL, Tielbeek A, Wiesinger B, Hak JB, Tielemans H, Ziemer G, Cristea E, Lansky A, Beregi JP. Sirolimus-eluting stents for the treatment of obstructive superficial femoral artery disease: Six-months results. Circ. 2002; 106: 1505 -1509. Dake MD. Are all drugs equal and do we need polymers? Paper presented at: Cardiovascular and Interventional Radiological Society of Europe; September 15, 2008; Copenhagen, Denmark.