Updated BRS Data: Safety Issues and Long-Term Benefit Seo Suk Min Seoul St. Mary’s Hospital Cardiovascular Center 1 PCI and DES have revolutionized cardiovascular care 1977 1988 2001 - 2003 Andreas Gruentzig perfor Julio Palmaz and Richard Schatz de Drug-eluting stents are introduc ms the first PTCA in Zurich velop a stainless steel stent for cor ed to the European and U.S. ma , Switzerland onary applications rkets Balloon Angio Bare Coronary Drug- plasty1977 (PTCA) Metal Stents ( Eluting Stents BMS) (DES) • Continuous PCI technology advancements improved clinical outcomes for CAD • BVS represents a new approach transient vessel support with drug delivery capability without the long-term limitations of the metallic drug-eluting stents (DES) *Additional sizes received CE Mark in August 2012. 2 2 Potential Fate of Vessels Stented with DESs Delayed Healing Stent Thrombosis? * uncovered struts1 Benign, low grade, Non-occlusive Neo-Atheroma Stent Thrombosis? In-Stent Restenosis (symptomatic or asymptomatic) Late Acquired Malapposition Stent Thrombosis? 3 Information contained herein for distribution outside the U.S. only. AP2940435-OUS Rev. A 09/14 Despite improvements in PCI, there is evidence of unmet need with current treatment options Long-term BMS event rate1 Long-term DES event rate2 1. Yamaji K, et al. Very long-term (15 to 20 years) clinical and angiographic outcome after coronary bare metal stent implantation. Circ Cardiovasc Interv 2010;3(5):468-75. 2. SPIRIT III: Ischemia-driven TLR through 5 years. Stone GW, TCT 2011. 4 4 Three Approaches to Improve Early and Late DES Outcomes 1. Metallic DES with bioabsorbable polymers 2. Metallic DES, polymer-free 3. Bioresorbable scaffolds (BRS) =(BVS) 5 Bioresorbable Vascular Scaffolds (BRS) Igaki-Tamai PLLA (poly-L-lactic acid) PLLA Abbott Absorb (eluting everolimus) PLLA Elixir DESolve (eluting novolimus) Iodinated tyrosine- Reva Fantom derivative (eluting sirolimus) Magnesium Biotronik Dreams (eluting sirolimus) Absorb Bioresorbable Vascular Scaffold System Bioresorbable Bioresorbable XIENCE V Everolimus Scaffold Coating Delivery System All illustrations are artists’ renditions *Except for platinum markers 7 Novel Attributes of Other BRS Elixir DESolve • Self-correcting property PLLA • Over-expansion w/o fracture (eluting novolimus) • More rapid bioresoption / • Lumen growth after 6 mo Reva Fantom Iodinated tyrosine- • Able to rapidly deploy derivative • Over-expansion w/o fracture (eluting sirolimus) • Radio-opaque Biotronik Dreams Magnesium • Greater stretchable strength (eluting sirolimus) 8 Status of BRS • Either a polymer or metallic alloy • Polymeric BRS are mainly made of Poly-L-lactic acid (PLLA) or Poly- DL-lactic acid (PDLLA) • Iron and magnesium based alloys • CE mark in Europe • PLLA based Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascula, Temecula, CA) • PLLA based DESolve (Elixir. Sunnyvale, CA) • PLLA based Fantom (Reva medical) • Magnesium based DREAMS-2 (Biotronik SE, Berlin, Germany) 9 10 PCI and DES have revolutionized cardiovascular care 1977 1988 2001 - 2003 ? 2010* Andreas Gruentzig perfor Julio Palmaz and Richard Schatz de Drug-eluting stents are introduc First Absorb Bioresorbable Vascular S ms the first PTCA in Zurich velop a stainless steel stent for cor ed to the European and U.S. ma caffold (BVS) approved for use in Eur , Switzerland onary applications rkets ope and Asia-Pacific Bioresorbable Balloon Angio Bare Coronary Drug- Vascular Scaff plasty1977 (PTCA) Metal Stents ( Eluting Stents olds BMS) (DES) (BRS) *Additional sizes received CE Mark in August 2012. 11 11 Bioresorbable Vascular Scaffold (BRS): The ideal of leaving nothing behind After implantation After resorption 12 Vascular Reparative Therapy: Potential for Improved Long-Term Outcomes Substantial lumen enlargement due to plaque regression and adaptive remodeling IVUS OCT ABSORB Cohort A MLA 6.35 mm2 6 month f/u MLA 8.77 mm2 5 year f/u The ‘final golden tube’ R.J. van Geuns, PCR 2012. Images courtesy of Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands 13 Expected Advantages of BRS When First Introduced in the Market • Restoring physiologic vasomotor function • Late luminal gain late expansive remodeling • Overcome ‘jailing’ of the side branches • Ability to graft the stented segment • Reduce(?) the risk of stent thrombosis and the duration of dual antiplatelet therapy (DAPT) 14 Global Clinical and Commercial Experience Comprehensive Abbott-Sponsored Clinical Program 2011 2012 2014 2014 2015 2016 ABSORB Cohort A 5 Y n = 30; FIM ABSORB Cohort B 1 Y 2 Y 3 Y 4 Y 5 Y n = 101; FIM ABSORB EXTEND Enrollment & Follow-Up 1 Y 2 Y 3 Y n = 814, Registry ABSORB II Enrollment & Follow-Up 1 Y 2 Y 3 Y n = ~501, International RCT ABSORB FIRST Enrollment & Follow-Up 1 Y n = ~2,000, International Registry ABSORB III Enrollment & Follow-Up 1 Y 2 Y n = 2,235, US Pivotal RCT ABSORB Japan Enrollment & Follow-Up 1 Y 2 Y n = 400, Japan Pivotal RCT ABSORB China Enrollment & Follow-Up 1 Y 2 Y n = 440, China Pivotal RCT ABSORB IV* n = ~3,000, US RCT UK Registry Enrollment & Follow-Up 1 Y n = 1,000, UK Registry Total Patients Studied n=~599 n~965 n~5,709 n~7,609 n~8,709 n~9,709 15 Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease – ABSORB III trial • Objectives: to evaluate TLF of BVS or EES • Methods • 2008 pts c stable or unstable angina • randomly assigned in a 2:1 ratio to BVS or EES • 1’ end point: target lesion failure at 1 yr • a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven targetlesion revascularization Safety and Efficacy Outcomes at 1 Year Treatment of noncomplex obstructive CAD with BVS was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. 16 N Engl J Med 2015;373:1905-15. TLF by 2 Years Overall QCA RVD ≥ 2.25 mm HR [95%CI]=1.42 [1.04, 1.94] HR [95%CI]=1.35 [0.93, 1.96] p=0.03 p=0.12 30% 30% Absorb BVS (N=1322) Absorb BVS (N=1074) 25% 25% Xience CoCr-EES (N=686) Xience CoCr-EES (N=549) 20% 20% 15% 15% 10.9% 10% 10% 9.3% 5% 7.8% 5% 7.0% 0% 0% 0 13 25 0 13 25 Time Post Index Procedure (Months) Time Post Index Procedure (Months) No. at Risk: Absorb 1322 1193 1141 1074 982 943 Xience 686 634 608 549 512 496 Note: The 2-year window allowed follow-up through 25 months ACC 2017 Clinical Endpoints by 2 Years Overall QCA RVD ≥ 2.25mm Absorb XIENCE Absorb XIENCE (N=1322) (N=686) (N=1074) (N=549) TLF 11.0% (143)* 7.9% (53)* 9.4% (99) 7.0% (38) Cardiac Death 1.1% (14) 0.6% (4) 0.9% (10) 0.4% (2) TV-MI 7.3% (95)** 4.9% (33)** 6.5% (68) 4.8% (26) ID-TLR 5.3% (69) 4.3% (29) 4.1% (43) 3.0% (16) ST (Def/Prob) 1.9% (24) 0.8% (5) 1.3% (13) 0.6% (3) * P-value=0.03. ** P-value=0.04. P-value >0.05 for all other comparisons Note: The 2-year window allowed follow-up through 25 months ACC 2017 19 Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II) : a 3 year • Objectives: to evaluate long-term vasomotor function of BVS • Methods • 501 pts c myocardial ischemia and 1 or 2 vessel disease • randomly assigned in a 2:1 ratio to BVS or EES • 1’ : angiographic vasomotor reactivity after IC NTG (IVUS) • 2’ : angiographic late luminal loss Thrombosis endpoint The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non- inferior late luminal loss for BVS 20 Lancet 2016; 388: 2479–91. Absorb vs EES: a meta-analysis • 6 RCTs • 3738 pts • At 1 yr • 1’ efficacy outcome: target lesion revascularisation • 1’ safety outcome: definite or probable stent (scaffold) thrombosis Absorb similar rates of repeat revascularisation at 1 year of follow-up an increased risk of subacute stent thrombosis. Lancet 2016; 387: 537–44. 21 In total, definite/probable scaffold thrombosis occurred in 31 patients (3.5%) who received the Absorb device while stent thrombosis was documented in 8 patients (0.9%) who received the Xience stent (hazard ratio 3.87; 95% CI 1.78-8.42). Wykrzykowska JJ, et al. N Engl J Med 2017 22 23 DESolve Cx Bioresorbable Coronary Scaffold System • 120 µm strut thickness Improved deliverability • System crossing profile (0.053” - 1.3mm*) • 6 Fr (0.71” – 1.8mm) guide cat heter compatible • 0.014” wire compatible Alexandre Abizaid, TCT 2016 24 DESolve Bioresorbable Coronary Scaffold Expansion Capability . DESolve scaffold can be expanded up to 0.5 mm above nominal (per I FU) for optimal results . DESolve scaffold designed with a substantial margin for expansion to reduce the risk of strut fracture 3.4 mm 3.8 mm 4.0 mm 4.75 mm DESolve over-expa nded scaff DESolve 3.0 mm expans old ion capability compared to metallic stent Xience over-expan ded metal st ent 25 Data on file at Elixir Medical DESolve Nx Clinical Trial Pre-specified 6m and 36m QCA Analysis Paired Results 6 months 36 months In-Scaffold Analysis p-value N = 19 N = 19 RVD (mm) 2.94 ± 0.30 2.95 ± 0.33 0.76 MLD (mm) 2.56 ± 0.36 2.45 ± 0.45 0.20 LLL (mm) 0.12 ± 0.14 0.22 ± 0.33 0.20 Median Late Loss (mm) 0.09 [0.04; 0.13] 0.16 [0.04; 0.31] Diameter Stenosis (%) 13.06 ± 6.56 16.40 ± 13.47 0.37 Values are mean ± SD; % (n), or Median (interquartile range 25%, 75%) MLD – Minimum luminal diameter; LLL – late lumen loss.