Κλινικές μελέτες, απεικόνιση και αποτελέσματα βιοαπορροφήσιμων stents Ομάδες Εργασίας Αιμοδυναμικής και Επεμβατικής Καρδιολογίας Θεσσαλονίκη 21-2-2014 Ηλίας Α. Σανίδας MD, PhD, FESC, FACC, MAHA, MSCAI, MEAPCI Cardiovascular Research Foundation, New York, NY, USA
The history of PCI 1977 First balloon angioplasty 1990 s Bare metal stents Mid 2000 s Late 2000 s Early 2010 s 1 st generation drug eluting stents (Sirolimus, Paclitaxel) 2 nd generation drug eluting stents (Zotarolimus, Everolimus) Bioabsorbable scaffolds (Myolimus, Novolimus)
Different drugs (biolimus, novolimus) Thinner struts (cobalt chromium) Bioresorbable scaffolds Bioabsorbable polymers, or polymer free scaffolds
Bare Metal Stents ΠΛΕΟΝΕΚΤΗΜΑΤΑ Provide scaffolding Very low rates of late ST Short duration of DAPT Inexpensive ΜΕΙΟΝΕΚΤΉΜΑΤΑ High restenosis rates Permanent device issues
Drug Eluting Stents ΠΛΕΟΝΕΚΤΗΜΑΤΑ Provides scaffolding neointimal hyperplasia restenosis ΜΕΙΟΝΕΚΤΗΜΑΤΑ Up to 2% per year rate of late ST with high morbidity/mortality Requires long term DAPT Permanent device issues Θρόμβος
Bioresorbable Vascular Scaffold (BVS) Το νέο παράδειγμα Revascularization with Transient Support Mimicking DES 1 Επαναγγείωση Αποκατάσταση Restoration of Physiological Environment (shear stress, multidirectional motion, morphology) 3 2 Benign Resorption Αποδόμηση For a BVS, the goal is to provide temporary vessel support and then allow the physiology to evolve naturally
BVS is not a Metallic Stent Plastic from long lactate acid chains in crystals Polylactide Degradation vs. Radial Support Tie chains Crystal lamella Amorphous tie chains Support Molecular Weight Mass Loss 1 3 6 12 18 24 Mos
Bioresorbable scaffolds Company Stent Development Pre-clinical Clinical trials Post-market Kyoto Medical Igaki-Tamai Biotronik Dreams Abbott Absorb Art Art18AZ Reva Medical Resolve Xenogenics Ideal biostent Orbus Neich Acute Elixir DESolve Amaranth Amaranth PLLA Huaan Biotech Xinsorb S3V Avatar Meril MeRes Zorion Medical Zorion BRS Lifetech Lifetech Iron
Sufficient Support Inflammation Risk Restoration Αποκατάσταση Serruys PW, et al., Circulation 1988; 77: 361. Minimal Threshold for Support Strength Resorption 3 12 24 Time (Months) Scaffolding period is sufficient Post-PCI 6 Mos. n = 33 n = 33 p < 0.00001 24 Mos. n = 33 ABSORB Cohort B Serial Analysis Scaffold Lumen Area Area 6.53 mm 2 6.36 mm 2 1.7% 6.85 mm 2 Lumen Area 7.7%
Interventional Plaque Regression by BVS: Substantial lumen enlargement due to plaque regression with adaptive remodeling (cohort A pt) Pre-PCI Post-PCI 6 months 2 years 5 years Vessel area (mm 2 ) 15.72 15.34 14.09 13.76 Mean lumen area (mm 2 ) 6.95 6.17 6.56 8.09 Plaque area (mm 2 ) 8.78 9.17 7.54 7.07
Resorption Αποδόμηση ABSORB BVS 6 months 12 months 18 months 24 months 30 months 36 months XIENCE V
Overview of ABSORB studies N=30 2006 ------ 2009 2010 2011 2012 2013 2014 2015 Cohort A (n=30) 3-yr 4-yr 5-yr Lancet 2008 & 2009, Eurointervention 2010 Cohort B- G1 (n=45) 1-yr 2-yr 3-yr 4-yr 5-yr Cohort B- G2 (n=56) 1-yr 2-yr 3-yr 4-yr 5-yr EXTEND (n=1000) N=45 N=56 N=807 Follow-up (3-yr) Circ 2010, Circ int 2012 JACC 2012 Physiology (n=40) N=2 Follow-up (2-yr) EU RCT (n=500) N=501 Follow-up (3-yr) ACE ABSORB First (n=10,000) Grand total:1137 in (in 2015: Trials) 16971 pts US RCT (n=5000) Japan RCT (n=300) CE marked! N=677 N=171 Follow-up (5-yr) Follow-up (5-yr) China (n=200) N=80 Commercially available Follow-up Enrolled To be Enrolled Follow-up
Three-Year Clinical and Multimodality Imaging Results of the ABSORB Trial Cohort B1 (n = 45) with imaging at 180 days and 2 years and Cohort B2 (n = 56) with imaging at 1 and 3 years. Late loss increased from 0.17 mm at 6 months to 0.27 mm at 2 years; neointima increased 0.68 mm 2 on OCT MACE was 9.0% for the full cohort at 2 years and 6.8% for Cohort B1 at 3 years, with no scaffold thrombosis Vasomotion was demonstrated on QCA, while signs of bioresorption were accompanied by an increase in mean scaffold area Implications: At longer-term follow-up, late loss and neointima increased, but signs emerged of recovery of vascular function. Serruys PW. ACC 2013. San Francisco, CA.
DESolve I FIM Study MULTI-CENTER FEASIBILITY TRIAL Single De Novo Native Coronary Artery Lesions (Type A) Vessel Diameters: 2.75 3.0 mm Stent Diameters: 3.0 mm Lesion Length: 10 mm Stent Lengths: 14 mm Pre-Dilatation required / Post-Dilatation at physician discretion Polylactide-based Bioresorbable scaffold + Bioabsorbable polymer + Myolimus @ 3µg per mm Stent Length Clinical Follow-up Angiographic and /IVUS/OCT/MSCT Follow-up 30d 6mo 12mo 24 mo 3-5yrs Principal Angiographic Endpoint: Key Endpoints: Anti-Platelet Therapy for 12 months In-Stent Late Lumen Loss at 6 months (QCA) Device and Procedure (Clinical) Success Major Adverse Cardiac Events (Death, MI, or TLR) at 1, 6, 12mo and 2-5 yrs Clinically driven TLR, TVR and TVF at 1, 6, 12mo and 2-5 yrs Stent thrombosis rates at 1, 6, 12mo and 2-5yrs ABR, LLL and % volume obstruction, OCT assessment at 6 mo MSCT at 12 and 24 mo
prestenting poststenting (baseline) 6M FU 69-yr old male hyperlipidemia hypertension former smoker stable angina 6 month follow-up 6M FU 12M FU Verheye, Sanidas et al.
DESSOLVE I: First-in-Human Evaluation of a Bioabsorbable Polymer-Coated SES 30 patients with symptomatic CAD implanted with novel SES at 5 centers Over 18 months, QCA found low and steady late lumen loss, and improved MLD and percent diameter stenosis Multimodal imaging determined increased neointimal obstruction at 8 months, with no further progression at 18 months; proportion of uncovered stent struts decreased Overall MACE at 18 months was 3.3% with no deaths or stent thrombosis Conclusion: A novel bioabsorbable-polymer SES shows low and stable in-stent late loss, complete strut coverage, and good safety results in patients with de novo lesions at 18 months. Ormiston J, et al. JΑCC Intv. 2013.
A Next-Generation Bioresorbable Coronary Scaffold System-From Bench to First Clinical Evaluation Six- and 12-Month Clinical and Multimodality Imaging Results QCA, IVUS and OCT at baseline and 6 months and MSCT at 12 months Conclusions. The study demonstrated the feasibility and efficacy of the DESolve BCS, showing low in-scaffold late lumen loss, low % neointimal volume at 6 months, no chronic recoil and maintenance of lumen patency at 12 months. Verheye, Sanidas et al. JACC Interv. 2013
DESolve Nx Trial PROSPECTIVE, MULTI-CENTER TRIAL Geographical Principal Investigators: Alexandre Abizaid; Stefan Verheye; Joachim Schofer; Angiographic Core Lab: CRC IVUS/OCT/MSCT Core Labs: CRC Data Management: CRC Single De Novo Native Coronary Artery Lesions (A-B1); Non-target lesion treatment in a separate epicardial vessel Vessel Diameters: 2.75 3.5 mm Stent Diameters: 3.0, 3.25 and 3.5 mm Lesion Length: 14 mm Stent Lengths: 14 and 18 mm Pre-Dilatation required / Post-Dilatation at physician discretion Polylactide-based Bioresorbable scaffold + Bioabsorbable Polymer + Novolimus @ 5µg per mm Scaffold Length Enrollment: 120 patients in Europe, Brazil and New Zealand Clinical Follow-up Angiographic and /IVUS/OCT/MSCT (subset) Follow-up 30d 6mo 12mo 24 mo 3-5yrs Principal Angiographic Endpoint: Key Endpoints: Anti-Platelet Therapy for 12 months In-Stent Late Lumen Loss at 6 months (QCA) Device and Procedure (Clinical) Success Major Adverse Cardiac Events (Death, MI, or TLR) at 1, 6, 12 mo and 2-5 yrs Clinically driven TLR, TVR and TVR at 1, 6, 12mo and 2-5 yrs Stent thrombosis rates at 1, 6, 12mo and 2-5yrs ABR, LLL at 6 mo Subset of 35 pts: Angio, IVUS, OCT assessment at 6 and 24 mo; MSCT at 12 mo
BIOSOLVE-1: Safety and Performance of Drug-Eluting Absorbable Metal Scaffold (DREAMS) in Patients with De Novo Coronary Lesions First-in-man trial in 46 patients. 100% procedural and device success seen with paclitaxeleluting device Rate of target lesion failure (cardiac death, target-vessel MI, or clinically driven TLR) was 7% at 12 months Mean in-scaffold late lumen loss was 0.65 mm at 6 months and 0.52 mm at 12 months Implications: DREAMS shows improvement and continuing potential of a fully bioabsorbable DES, but late lumen loss remains a concern. Haude M, et al. Lancet. 2013;381:836-844.
Trial Clinical Outcomes With Bioabsorbable Polymer- Versus Durable Polymer-Based Drug-Eluting and Bare-Metal Stents Data from 89 trials including 85490 patients Conclusions. BP-BES were associated with superior clinical outcomes compared with BMS and first-generation DES and similar rates of cardiac death/mi, MI, and TVR compared with second-generation DP-DES but higher rates of definite ST than CoCr-EES. Palmerini et al. JACC Feb 2014.
Δυνητικά κλινικά οφέλη Αποκατάσταση αγγειακού τοιχώματος Αγγείο ελεύθερο για μελλοντικές επεμβάσεις Μείωση της επαναστένωσης? Μικρότερη διάρκεια DAPT? Λιγότερα επεισόδια θρόμβωσης?
Πρακτικά ζητήματα Σχετίζονται με τα υλικά του stent Αλληλοκάλυψη Διχασμοί Επανατοποθέτηση
Do s and Don ts DO Properly and carefully size the vessel Prep the lesion thoroughly Pay attention to expansion limits Overlap: Big balloon marker on small scaffold marker Bifurcations: Provisional or sequential balloons for 2 stent technique DON T Overextend the scaffold (< Ref Diam + 0.5 mm) Crushing for 2 stent bifurcation Use traditional kissing
Συμπεράσματα Αποτελούν την αρχή μιας νέας εποχής Το σημαντικότερο πλεονέκτημα είναι ότι επιτρέπουν στο αγγείο να επιστρέψει στη αρχική του κατάσταση Τα πρώτα δεδομένα είναι ενθαρρυντικά, αλλά αναμένονται τα αποτελέσματα των μεγάλων τυχαιοποιημένων μελετών που βρίσκονται σε εξελιξη Χρειάζονται απαραίτητα σωστή προετοιμασία πριν και ιδιαίτερη προσοχή κατά την τοποθέτηση Προβλέπεται ότι θα αποτελέσουν την θεραπεία πρώτης γράμμης στις διαδερμικές επεμβάσεις