Βιοαποδοµήσιµα ενδοαγγειακά ικριώµατα Αθηνόδωρος Ν. Νικητόπουλος Επεµβατικός Καρδιολόγος Επιστηµονικός Συνεργάτης Β ΚΚ ΑΠΘ Ιατρικό Διαβαλκανικό Κέντρο IICE 2016, Θεσσαλονίκη 8/9/2016
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History of Angioplasty First stainless steel Stent inserted in human artery 1986 Drug eluting stents introduced to EU and USA markets 2001-2003 1977 First Coronary Angioplasty Dr. Andreas Gruentzig 1999 First bioabsorbable PLLA stent in human coronary arteries (Igaki- Tamai) 2006 30 patients enrolled in the first ever human clinical trial testing a fully Bioabsorbable Drug-eluting Stent (ABSORB trial, Abbott)
Πλεονεκτήµατα των BMS (1986-) (απέναντι σε POBA) Αντιµετώπιση της αγγειακής επαναφοράς (recoil) Μείωση του κινδύνου διαχωρισµού Μείωση του κινδύνου εµφράγµατος και ανάγκης επαναγγείωσης
Πλεονεκτήµατα των DES (2001-) (απέναντι σε BMS) Περιορισµός της διαδικασίας ενδοθηλιοποίησης και κατά συνέπεια της επαναστένωσης Περαιτέρω µείωση του κινδύνου εµφράγµατος και της ανάγκης επαναγγείωσης
Μειονεκτήµατα των DES Κίνδυνος όψιµης και πολύ όψιµης θρόµβωσης Ηµιτελής ενδοθηλιοποίηση Ηµιτελής επαφή µε το αγγειακό τοίχωµα (malapposition) Κάταγµα της πρόθεσης Ενδοθηλιακή δυσλειτουργία Νεοαθηρωµάτωση Επηρεασµός της αγγειακής κινητικότητας Χρόνια φλεγµονώδης διαδικασία, λόγω του πολυµερούς µέσου Μακρά διάρκεια της αντιαιµοπεταλιακής αγωγής Μειωµένη ευχέρεια για εµφύτευση αορτοστεφανιαίων µοσχευµάτων Δυσχέρεια στην πραγµατοποίηση ακτινοδιαγνωστικών εξετάσεων Μακροπρόθεσµη ανάγκη για επαναγγείωση 2,2% ετησίως
FIRST BIORESORBABLE SCAFFOLD The Igaki-Tamai stent Used in 1998 PLLA-based BRS,160µm thick, self-expandable when heated; consequently, contrast dye at 80C is used for balloon inflation. Expansion continues at body temperature until dilation and vessel wall resistance reach equilibrium. In 2000, Tamai et al. reported initial results from 15 patients in whom 25 stents were successfully implanted.
ABSORB BVS
DESolve 1 st unique feature: Fracture Resistant EXPANSION CAPABILITY DESolve 3.0 mm expansion capability similar to metallic stent XIENCE V is a registered trademark of Abbott Vascular. DESolve is CE Mark Approved; Not available for sale in the US Data on file at Elixir Medical PMN 324 Rev A
DESolve : Fracture resistance 3 RD PARTY VERIFICATION 1 ML8 Absorb DESolve MB balloon diam and pressure (5.5mm, 22atm) No fractures Safe threshold 3.9mm @ 20atm Safe threshold 5.0mm @ 20atm SB dilatation with a 3.0mm NC balloon No fractures Safe threshold is 10atm No fractures Mini-KBPD with 2 NC balloons (3.0mm) No fractures Safe threshold is 5atm No fractures Summary of post-dilatation strategies and safe thresholds for Xpedition/ML8, Absorb and DESolve 1. J Ormiston, An independent bench comparison of two bioresorbable drug-eluting coronary scaffolds (Absorb and DESolve) with a durable metallic drug-eluting stent (ML8/Xpedition). Eurointervention, Feb 2015 Testing conducted on DESolve platform with 150µm strut thickness DESolve is CE Mark approved. Not available for sale in the U.S. PMN 324 Rev A
DESolve 2 nd unique feature: Self Correction SELF CORRECTION TO NOMINAL DIAMETER DESolve is CE Mark approved. Not available for sale in the U.S. PMN 324 Rev A
DESolve : Self Correction 3 RD PARTY VERIFICATION 1 Recoil. Scaffold (or stent) external diameter immediately after deployment, at 1 minute, 10 minutes, then at 1 hour. 1. J Ormiston, An independent bench comparison of two bioresorbable drug-eluting coronary scaffolds (Absorb and DESolve) with a durable metallic drug-eluting stent (ML8/Xpedition). Eurointervention, Testing conducted Feb 2015 on DESolve platform with 150µm strut thickness DESolve is CE Mark Approved; Not available for sale in the US PMN 324 Rev A
DESolve Serial IVUS Results 9% 6 month lumen growth Scaffold and Lumen Area N L = 40 Post Procedure 15.7% P = < 0.001 6 months 9.0% P = < 0.005 No Late Acquired ISA No aneurysm formation N L = Number of lesions. Mean volume for patients with incomplete scaffold apposition (ISA), One patient with persistent ISA DESolve Nx Study data on file at Elixir Medical DESolve is CE Mark Approved; Not available for sale in the US PMN 324 Rev A
DESolve Nx Clinical Trial 6 to 36 Mos Clinical Outcomes Hierarchical Events 0 to 1080 days, n (%) 6M (N=122) 12M (N=122) 24M (N=122) 36M (N=122) Major Adverse Cardiac Events 3.3% 5.7% 7.4% 8.2% Cardiac Death 1 (0.8%) 2 (1.6%) 3 (2.5%) 4 (3.3%) Target vessel MI 1 (0.8%) 1 (0.8%) 1 (0.8% ) 1 (0.8% ) Q-wave MI 0 0 0 0 Non-Q- wave MI 1 (0.8%) 1 (0.8%) 1 (0.8%) 1 (0.8%) Clinically Indicated-TLR 2 (1.6%) 4 (3.3%) 5 (4.1 %) 5 (4.1 %) Definite Stent Thrombosis 0 0 0 0 M. Leon, DESolve NX Trial 3- year Clinical and Imaging Results, TCT 2015 And DESolve Nx Study data on file at Elixir Medical DESolve is CE Mark approved; Not available for sale in the U.S. PMN 324 Rev A
DESolve Serial OCT Imaging Up to 3 Years In-vivo Confirmation of Bioresorption: Golden Tube Post-Procedure 6 Months 18 Months 36 Months A. Abizaid, Instituto Dante Pazzanese, Sao Paulo, Brazil DESolve is CE Mark approved; Not available for sale in the U.S. PMN 324 Rev A
Potential advantages of BRS
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POTENTIAL BENEFITS 1. Multiple imaging analyses reveal beneficial plaque stabilization and sealing caused by BRS-induced remodeling although the clinical impact needs further assessment. 2. Because BRS dissolve, this risk of length induced thrombosis may be reduced. 3. Reduced neointimal tissue growth,neoatherosclerosis and chronic inflammation risks as reactions to a permanent metal implant in DES. Because the BRS coating is degradable stent thrombosis stimulus is absent.
4. One of the fascinating aspect is late lumen enlargement in numerous patients with the Absorb bioresorbable vascular scaffold (BVS) and DESolve BRS observed by IVUS and OCT. 5. The initial mechanical flexibility of some BRS reduces their influence on biomechanical properties and blood flow. 6. Minor malapposition can be resolved by BRS self-correction, and its degradation avoids long-term malapposition. 7. Because there is no long-term vessel caging, abnormal shear stress may be reduced, as seen with preserved vasomotion.
MATERIAL COMPOSITION AND PROPERTIES The optimal BRS should ensure adequate shortto mid-term scaffolding of the previously stenosed vessel to avoid recoil and completely dissolve afterward to prevent side effects. Thus, temporarily sufficient radial support is needed, with struts as thin as possible. The optimal duration until full resorption is not yet defined. To achieve these goals, a considerable variety of materials and designs are under investigation.
During the first 6 months, minimal lumen diameter decreased and then constantly increased to 2.22 ±0.56 mm at the 3-year follow-up. IVUS analysis showed almost constant stent cross-sectional area after 1, 2, and 3 years, whereas minimal lumen cross sectional area decreased from 5.44 mm2 immediately after the procedure to 3.64 mm2 after 6 months, then increased to 5.18 mm2 after 3 years. During the follow-up period, a total of 14 TLRs, 1 acute scaffold thrombosis and 1 very late scaffold thrombosis, 1 lesion-related myocardial infarction, and 1 cardiac death were noted. Accordingly, cumulative TLR rates per patient were 16% after 1 and 3 years, 18% after 5 years, and 28% after 10 year
Limitations: Implantation requires an 8-French guiding catheter. The heated contrast dye may cause vessel wall injury. A new version of the device is currently undergoing pre-clinical evaluation.
First introduced in 1998 but forgotten due to the success of BMS and, later, DES. With long-term data and the revelation of the risks of metal stents, BRS development was reinitiated, resulting in a variety of devices.
POLY L LACTIC ACID Most commonly used substrate. Most have strut thickness ~150µm but as low as 100µm are under development Radial strength same as modern DES. Degradation by hydrolysis to lactic acid which is metabolized into carbon dioxide and water. complete degradation achieved in 1 to 3 years
MAGNESIUM Superior radial strength. Earlier devices lacked the anti proliferative drug. The electronegative charge that emerges during the degradation of metal BRS is antithrombotic. Degradation takes between 2 and 12 months. End products(corrosion) : inorganic salts. Offers 9 to 12 months of radial support. Advantage of having thinner struts due to high tensile strength.
OTHER MATERIALS Tyrosine polycarbonate(experimental) 6 months of radial support Resorption-24 and 36 months. Final products of degradation are ethanol, water, carbon dioxide
CURRENT LIMITATIONS Absence of large RCTs Experience in complex cases (bifurcation,ostial,cto) is limited and in such cases IVUS should support BRS implantation. High strut thickness may lead to vessel injury, nonlaminar flow, platelet deposition, and poor deliverability
Calcification or tortuosity are technically challenging. Regardless of lesion anatomy, pre-dilation is mandatory;direct stenting is not possible. Predilatation makes the system prone for dissection and ischemia.
Only limited scaffold sizes are currently available, and special facilities are needed for storage of some. Due to these technical particularities, the total cost and duration of PCI with a BRS may be higher than with a conventional DES. Duration of DAPT with BRS is unclear.
Current BRS limitations will likely be resolved in the future. Although their advantages already outnumber their disadvantages, large, randomized, controlled trials are still needed.