Le retour des stents auto-expansibles ? Didier CARRIE CHU TOULOUSE RANGUEIL High Tech Marseille Jeudi 26 Janvier 2012 Aucun conflit d’intérêt

1986 : 1ère implantation de stent coronaire Jacques Puel WALLSTENT IVA PROXIMALE

POURQUOI CE RETOUR 25 ANS APRES ? MEILLEURE CONNAISSANCE DU VAISSEAU MALAPPOSITION THROMBOSE INTRASTENT

DE LA PLAQUE D ’ATHEROSCLEROSE EVOLUTION DE LA PLAQUE D ’ATHEROSCLEROSE REMODELAGE VASCULAIRE Surface de la lumière longtemps conservée, tant que la surface de la plaque est < 40% de la surface totale de la paroi vasculaire Défaut de remodelage accidents aigus Glagov NEJM 87; Mc Pherson 86-92

Risque : sous dimensionner le stent dans le SCA Le vasospasme comme conséquence des STEMI IRA-proximal IRA-distal 4 3.48* 3.15 Diamètre coronaire (mm) 2.42* 2 1.96 *: p<0.05 vs basal Basal (+nitrés) Après stent a-bloqueurs IRA : Infarct related artery Risque : sous dimensionner le stent dans le SCA Gregorini et al. Circulation 1999;99:482

Pôle Cardiovasculaire et Métabolique Cook S, Circulation 2007 Pôle Cardiovasculaire et Métabolique

Predictors of stent thrombosis (ACS/STEMI) Van Werkum JW, JACC 2009

Pôle Cardiovasculaire et Métabolique Concept Self-expanding, Self apposing Nitinol stent which can increase in size after implantation Reduce acute and acquired malapposition Minimize embolization and no-reflow by avoiding aggressive post dilatation Pôle Cardiovasculaire et Métabolique

Radial force Data on Stentys files

SITUATIONS ANATOMIQUES POTENTIELLEMENT FAVORABLES ? Syndrome Coronaire Aigu ST+ (thrombus) Incongruence Artérielle ou veineuse Bifurcation

Background: stent sizing dilemma in STEMI 3.0? 3.5? 3.0 3.5 Malapposition Underexpansion Overdilation Stent thrombosis No reflow Restenosis Dissection/ Perforation

Pôle Cardiovasculaire et Métabolique OCT à 9mois Gonzalo et al Jacc Intervention 2009 Pôle Cardiovasculaire et Métabolique

STENTYS Clinical Proof Study Indication Stent Follow-up # patients MACE OPEN I Bifurcation DES 6 months 27 3.7% APPOSITION I & II STEMI BMS 12 months 68 8.8% APPOSITION III BMS/ DES 30 days, interim 600 3.8% all patients, 2.4% Cohort B* * In Cohort B (N=210), post dilatation was generally recommended, at low pressures OPEN I: S. Verheye et al., Eurointervention 2011;7:580-587 APPOSITION I & II – 12 month results presented at TCT 2011 by S. IJsselmuiden APPOSITION III – interim 30 day results presented at TCT 2011 by K.T. Koch

APPOSITION I DESIGN: Prospective, non-randomized, single-arm, multi-center feasibility study OBJECTIVE: To evaluate the safety and efficacy of the STENTYS® stent in AMI ENDPOINTS: Stent apposition and expansion at 3 days MACE at discharge and at 30 days Independent monitoring: Medpass Core lab: Cardialysis Statistical analysis: INSERM U970 (Paris); Prof. J.P. Tijssen (Amsterdam) 25 patients enrolled between March 2009 and October 2009 in 5 European clinical sites 25 patients with STENTYS® stent Angiographic and IVUS follow-up at 6 months IVUS at 0 and 3 days Clinical follow-up at 30 days Post-PCI IVUS image of a STENTYS stent in AMI patient IVUS image 3 days after procedure in this patient: 19% increase in reference lumen area Results: IVUS at baseline and 3 days Mean Reference area (distal) (mm²) +19% Mean Stent area (mm²) +18% Mean Lumen area (mm²) +17% Minimum Lumen area (mm²) p<0.02 G. Amoroso et al. EuroIntervention 2011;7:428-436

Pôle Cardiovasculaire et Métabolique 20% lumen area increase At implantation 3 day follow-up Pôle Cardiovasculaire et Métabolique

Pôle Cardiovasculaire et Métabolique Evolution over time Baseline 6 months 2 years Pôle Cardiovasculaire et Métabolique

Long term expansion by IVUS Stabilization of stent expansion below unconstrained diameter (6.5mm) +25% +3% Mean stent diameter Time Pôle Cardiovasculaire et Métabolique

APPOSITION II DESIGN: International, prospective, randomized, two-arm multi-center trial OBJECTIVE: To compare the STENTYS® Stent with balloon-expandable stents in AMI ENDPOINTS: Stent strut apposition and expansion at 3 days (measured by OCT) MACE @30 days and 6 months Independent monitoring: Genae Core Lab: Cardialysis 80 STEMI patients enrolled between 12/09 and 06/10 in 9 European centerssites STENTYS® stent Clinical follow-up at 30 days and 6 months Invasive follow-up at 3 days (QCA, OCT) VISION / Driver p<0.001 Balloon-expandable Stent - Day 3 STENTYS® Stent – Day 3 Patients with Stent Malapposition Presented by R.J. van Geuns & S.Verheye at TCT 2010 * Stent Malapposition defined as more than 5% of struts malapposed under OCT.

STENTYS® Coronary Stent Balloon vs Self-expanding Day 0 Day 3 Balloon-expandable stent STENTYS® Coronary Stent

Optical Coherence Tomography Stentys n=40 Control n=36 P Value Post-PCI Mean Lumen area (mm2) 7.88 ± 2.32 8.92 ± 2.22 NS Mean Stent area (mm2) 7.57 ± 2.29 8.95 ± 2.38 Stent volume (mm3) 191 ± 65 210 ± 83 3 days follow-up 8.99 ± 2.39 8.81 ± 2.18 9.02 ± 2.36 8.76 ± 2.26 228 ± 72 206 ± 86 15% increase 20

APPOSITION III DESIGN: Prospective, non-randomized, single-arm, multi-center trial OBJECTIVE: To evaluate the safety and performance of the STENTYS stent in routine clinical practice in a large population of STEMI patients PRIMARY ENDPOINT: MACE at 12 months SECONDARY ENDPOINTS: MACE at 30 days and 24 months PROCEDURAL GUIDELINES on post-dilatation: Cohort A: only when residual stenosis > 30% Cohort B: recommended, at low pressures 1000 patients to be enrolled in 40 European clinical sites 600 patients enrolled to date Cohort A: 390 patients Cohort B: 210 patients Clinical follow-up at 30 days Interim analysis Interim results: MACE at 30 days All patients (N=600) Cohort B (N=210) Death 0.8% 0.9% Re-AMI 1.5% 1.0% Clinically-driven TLR 0.5% Total 3.8% 2.4% MACE at 30 days in STEMI trials Interim results presented at TCT 2011 by K. Koch

APPOSITION IV Study Design DESIGN Prospective, randomized, two- arm multi-center study OBJECTIVE To compare the endothelization of the STENTYS® DES with a balloon- expandable DES in AMI ENDPOINTS % of uncovered struts at 4 & 9 months MACE up to 12 months 60 STEMI patients STENTYS® DES stent Conventional DES stent Time need for endotheliazation OCT & QCA at 4 & 9 months months Clinical FU at 12 months 22

SITUATIONS ANATOMIQUES POTENTIELLEMENT FAVORABLES ? Syndrome Coronaire Aigu ST+ (thrombus) Incongruence Artérielle ou veineuse Bifurcation

Pôle Cardiovasculaire et Métabolique Courtesy of Dr Souteyrand (Clermont-Ferrand) Pôle Cardiovasculaire et Métabolique

SITUATIONS ANATOMIQUES POTENTIELLEMENT FAVORABLES ? Syndrome Coronaire Aigu ST+ (thrombus) Incongruence Artérielle ou veineuse Bifurcation

SELF-EXPANDING STENT PLATFORM DEDICATED BIFURCATION STENT Conical shape Does no cover the carina itself SELF EXPANDING STENT Nitinol platform Excellent wall apposition Spans both vessels at the same time Two models: Reference diameter 3.0 ± 0.25 mm Max*. proximal stent diameter = 3.75 mm Max*. distal stent diameter = 6.00 mm Reference diameter 3.5 ± 0.25 mm Max*. proximal stent diameter = 4.25 mm Max*. distal stent diameter = 6.50 mm Lengths 11 and 14 mm

The Axxess™ stent implantation sequence Two wires 1 Position 2 Deploy partially at carina 3 Advance 4 4 Deploy 5 Sheath off 6 Simulations Simulations

Biolimus A9TM / Abluminal Biodegradable Polymer Bifurcation DES Axxess™ Clinical Program AXXESS PLUS N=139 DIVERGE N=302 AXXENT N=33 France and Germany Pilot study using bare metal stent Axxess Platform In-segment restenosis at 6 months 6 month follow-up completed, study completed Europe, Brazil and New Zealand FIM Safety and performance evaluation of Axxess DES In-stent late loss at 6 months 5 year follow-up completed, study completed Europe, Australia and New Zealand Evaluated best practices from AXXESS PLUS MACE1 at 9 months 3 year follow-up available, follow-up planned up to 5 years Europe Pilot study for Axxess Left Main DES MACE2 at 6 months 12 month follow-up available, study completed COBRA3 N=40 Randomized multicenter trial to compare Axxess DES along with BioMatrix Flex™ with Cullotte technique using Xience V® Stent strut coverage assessed by OCT at 9 months Enrolling

DIVERGE - MACE Components 3-year Outcomes Death MI id-TLR Agostoni P., oral presentation, EuroPCR 2011 Any In-segment bifurcation restenosis: 6.4% (9/140 at 9 months)1,2 Verheye S. et al, J Am Coll Cardiol, 2009 Verheye S. et al, oral presentation, TCT 2009 Pôle Cardiovasculaire et Métabolique

DIVERGE - Stent Thrombosis up to 3 Years Protocol ARC Definite* Probable Possible Acute (In-hospital) Subacute (30 days) 0.7% Late (>30 days - 1 year) 0.3%§ Very Late (1 year - 3 years) 1.0% 2.4% Pôle Cardiovasculaire et Métabolique

Pôle Cardiovasculaire et Métabolique CONCLUSION Balloon-expandable stents’ efficacy may be limited by : - Mal apposition - Over expansion - Side branch occlusion Stentys® and Axxess self-apposing stents for STEMI and Bifurcation have been proven : To be feasible To be safe To be effective ? Pôle Cardiovasculaire et Métabolique

Strut Width µ Data on Stentys files