Absorbable Scaffolds the Future of Coronary Interventions?

Transcription

1 Absorbable Scaffolds the Future of Coronary Interventions? Brock Cookman, DO, MSA Interventional Cardiology Mercy Heart and Vascular Institute April 8, 2017

2 None Disclosures

3 Objectives History of cardiac catheterization Bioresorbable Vascular Scaffolds (BVS) Future technology

4 90 years of Interventional Cardiology 1929 Werner Forssmann of Germany Became obsessed with attempting to take a catheter into a patient s heart; rejected by superiors Ignored his chief, found a willing assistant and tied her to a table. Afterwards he anesthetized his lower arm, inserted a urinary catheter into his antecubital vein up to 65 cm. He walked to the radiology department and documented the tip of the catheter in the right ventricle 1956 Nobel Prize for Physiology and Medicine

5 90 years of Interventional Cardiology 1958 Mason Sones at the Cleveland Clinic During aortography of a patient with valvular heart disease, the catheter accidently entered the right coronary artery with injection of approximately 30 cc of contrast Procedure aborted transient heart block that recovered I knew that night that we finally had a tool that would define the anatomic nature of coronary artery disease

6 90 years of Interventional Cardiology 1970s First angioplasty - Dr. Andreas Gruentzig. University Hospital in Zurich, Switzerland 10 years after first coronary artery bypass grafting procedure

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8 90 years of Interventional Cardiology 1980s Improvement in equipment, catheters, guidewires, balloons, etc. Issues - Elastic recoil after angioplasty First stent inserted into a human artery. Toulose, France. Drs. Jacques Puel and Ulrich Sigwart

9 90 years of Interventional Cardiology 1990s Gianturco-Roubin Flex stent approved by U.S. FDA Treatment of abrupt closure after angioplasty Palmaz-Schatz stent approved by FDA for elective implantation More than 1 million angioplasties performed worldwide Issues - high restenosis rate

10 90 years of Interventional Cardiology 2000s Almost 2 million angioplasties performed worldwide First drug-eluting stent approved by the U.S. FDA More than 2 million coronary angioplasties performed worldwide each year. Second generation drug-eluting stents Radial artery catheterization

11 90 years of Interventional Cardiology 2010s Third/Fourth generation drug eluting stents Bioabsorbable scaffolds Drug coated balloons Intracoronary imaging/assessment FFR/iFR OCT IVUS Structural Heart disease Aortic - TAVR Mitral - Tendyne, MitraClip

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13 Structural Heart Disease - TAVR

14 Structural Heart Disease - Mitral

15 Bioresorbable Vascular Scaffolds Abbott Vascular Absorb GT1 Constructed of PLLA (poly L-lactic acid) Everolimus eluting Fully resorbable over 3 years FDA approval July 5, 2016

16 Background Absorb BRS was CE-mark approved in December 2010 based on the data of the first in man trial (ABSORB Cohort B trial). At the time of the study design in July 2011, clinical evidence has been attained without use of a comparator (Xience). * The absorb II study has been powered to demonstrate two mechanistic co primary end points Superiority of the bioresorbable scaffold Absorb on the metallic stent Xience in vasomotion post intracoronary nitrate Non inferiority in late loss post intracoronary nitrate *Serruys et al. Lancet October 30, :30 (GMT)

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18 Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: ABSORB III Trial 2-Year Results Stephen G. Ellis, MD, Dean J. Kereiakes, MD, and Gregg W. Stone, MD for the ABSORB III Investigators

19 ABSORB III/IV Program Objectives Two integrated randomized trials designed to: Short-term: Demonstrate similar (non-inferior) results with Absorb BVS compared to Xience CoCr-EES Long-term: Demonstrate superior results with Absorb BVS compared to Xience CoCr-EES

20 Study Flow and Follow-up Randomized 2:1 N=2008 (ITT) ABSORB N=1322 Xience N=686 N=4 lost to follow-up N=6 withdrew consent N=6 lost to follow-up N=3 withdrew consent ABSORB N=1312 ABSORB N=1296 N=10 lost to follow-up N=6 withdrew consent 1-Year Follow-up 99.2% Complete 98.7% Complete 2-Year Follow-up N=4 lost to follow-up N=2 withdrew consent 98.0% Complete 97.8% Complete Xience N=677 Xience N=671

21 Baseline Characteristics Patient Characteristics Absorb (N=1322) (L=1385) Xience (N=686) (L=713) p-value Age (mean) 63.5 ± ± Male 70.7% 70.1% 0.80 Diabetes 31.5% 32.7% 0.60 Unstable angina 26.9 % 24.5% 0.25 Lesion Characteristics Lesion length, mm 12.6 ± ± RVD, mm 2.67 ± ± DAPT Usage DAPT at 1 year 90.2% 90.7% 0.72 DAPT at 2 years 66.0% 65.6% 0.84 As previously published, there were no major inter-group differences between baseline patient and lesion characteristics Ellis SG et al. N Engl J Med 2015;373:

22 ABSORB III Very Small Vessel Analysis at 1 Year The primary endpoint of 1-year TLF non-inferiority was met ABSORB III eligibility criteria included vessels with RVD 2.5 mm 3.75 mm (visual estimation) ~19% of patients had a target lesion with RVD <2.25 mm by QCA (correlates with visual estimate ~2.5 mm) Post-hoc subgroup analysis revealed an increased 1-year risk associated with treating very small vessels (QCA RVD <2.25 mm) In collaboration with the FDA, Absorb IFU was updated with specific guidance to avoid BVS implantation in vessels with RVD <2.5 mm

23 Clinical Endpoints by 1 Year (13 Months) Overall QCA RVD 2.25mm Absorb (N=1 322) XIENCE (N= 686) Absorb (N=1 074) XIENCE (N= 549) TLF 7.8% (102) 6.1% (41) 6.7% (71) 5.5% (30) Cardiac Death 0.6% (8) 0.1% (1) 0.6% (6) 0.2% (1) TV-MI 6.0% (79) 4.6% (31) 5.2% (55) 4.6% (25) ID-TLR 3.0% (40) 2.5% (17) 2.2% (24) 1.5% (8) ST (Def/Prob) 1.5% (20) 0.7% (5) 0.9% (9) 0.6% (3) P-value >0.05 for all comparisons Note: The 1-year window allowed follow-up through 13 months

24 TLF Between 1 and 2 Years (13 25 Months) 20% Overall HR [95%CI]=1.45 [0.83, 2.52] p= % QCA RVD 2.25 mm HR [95%CI]=1.71 [0.84, 3.47] p=0.13 Absorb BVS (N=1322) Absorb BVS (N=1074) 15% Xience CoCr-EES (N=686) 15% Xience CoCr-EES (N=549) 10% 10% 5% 3.7% 5% 3.2% 0% 2.6% 0% 1.9% Months Post Index Procedure Months Post Index Procedure No. at Risk: Absorb Xience Note: The 1-year window allowed follow-up through 13 months, and the 2-year window allowed follow-up through 25 months

25 Clinical Endpoints from 1 to 2 Years (13 to 25 Months) Overall QCA RVD 2.25mm Absorb (N=1 322) XIENCE (N= 686) Absorb (N=1 074) XIENCE (N= 549) TLF 3.7% (47) 2.5% (17) 3.2% (33) 1.9% (10) Cardiac Death 0.5% (6) 0.4% (3) 0.4% (4) 0.2% (1) TV-MI 1.3% (17) 0.7% (5) 1.3% (14) 0.4% (2) ID-TLR 2.6% (33) 1.8% (12) 2.2% (23) 1.5% (8) ST (Def/Prob) 0.3% (4) 0.0% (0) 0.4% (4) 0.0% (0) P-value >0.05 for all comparisons Note: The 1-year window allowed follow-up through 13 months, and the 2-year window allowed follow-up through 25 months

26 Scaffold Thrombosis Rates Between 1 and 2 Years in Perspective 5. Absorb Arm Absorb Arm ST (definite or probable) between 1 and 2 years (%) ABSORB II ABSORB Japan ABSORB China ABSORB III (N=335) (N=266) (N=241) (N=1322)

27 TLF by 2 Years (25 Months) Overall HR [95%CI]=1.42 [1.04, 1.94] p=0.03 QCA RVD 2.25 mm HR [95%CI]=1.35 [0.93, 1.96] p= % 30% 25% Absorb BVS (N=1322) Xience CoCr-EES (N=686) 25% Absorb BVS (N=1074) Xience CoCr-EES (N=549) 20% 20% 15% 10% 10.9% 15% 10% 9.3% 5% 7.8% 5% 7.0% 0% 0% Time Post Index Procedure (Months) Time Post Index Procedure (Months) No. at Risk: Absorb Xience Note: The 2-year window allowed follow-up through 25 months

28 Clinical Endpoints by 2 Years (25 Months) Overall QCA RVD 2.25mm Absorb (N=1 322) XIENCE (N= 686) Absorb (N=1 074) XIENCE (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

29 Limitations ABSORB III enrolled patients with stable ischemic heart disease and stabilized ACS, and excluded specific complex lesions (e.g. CTO, LM, large bif); results may therefore not be generalizable to higherrisk patients and more complex disease Underpowered for low frequency events BVS is a first generation device and was used for the first time by most operators within this trial The optimal implantation technique was still evolving during the initiation and enrollment of ABSORB III

30 Impact of Implantation Technique Implantation technique for Absorb BVS has evolved in recent years A growing body of evidence from the ABSORB clinical trials and registries suggest that optimal implantation techniques may improve clinical outcomes These optimal techniques have been described as PSP - Pre-dilatation, appropriate vessel Sizing, and high pressure Post-dilatation We therefore performed an analysis in the ABSORB III trial to evaluate the impact of PSP

31 Very Late Scaffold Thrombosis Case Reviews Case number Category VLST VLST VLST VLST Time (day) Target Mid RCA Prox RCA Prox LAD Dist RCA Pre-procedure QCA Reference diameter (mm) Procedure Nominal size of scaffold Deployment pressure (atm) Post-dilatation Yes Yes Yes Yes NC Balloon size (mm) Maximum pressure (atm) PSP No No No No Characteristics at time of event Aspirin alone or DAPT Aspirin alone DAPT DAPT DAPT Clinical Presentation NQMI QMI NQMI QMI

32 Impact of PSP * on TLF and ST (Def/Prob) by 2 Years (25 Months) Events through 2 years (%) Absorb without PSP (N=1147 [92%] Absorb with PSP (N=95 [8%]) All Xience (N=735) As Treated Population TLF ST (Def/Prob)

33 Blinded, Pooled, Interim ABSORB IV Outcomes: Comparison to ABSORB III ABSORB III: 2008 pts randomized 2:1 BVS:EES (1322:686) ABSORB IV: 3000 pts being randomized 1:1 BVS:EES ABSORB III Pooled (N=2008) 1 ABSORB IV Pooled (N=2546) 2,3 QCA RVD < 2.25 mm 19% 4% Post-dilatation (BVS) 66% 84% Pooled Stent/Scaffold Thrombosis 30 days 0.9% 0.4% 1 year 1.1% 0.5% 1. Assuming the observed event rates for each arm in ABSORB III, but adjusted for the 1:1 randomization ratio in ABSORB IV. The actual observed pooled ST rates in ABSORB III were 1.0% at 30 days and 1.3% at 1 year. 2. Based on February 15, 2017 data cut (N=2397 with 30-day FU and N=1415 with 1-year FU). 3. ABSORB IV includes ~25% non A-III like subjects (troponin+ ACS, 3 lesions treated, and planned staged procedures).

34 Summary and Conclusions In the large-scale randomized ABSORB III trial, the safety and efficacy profile of Absorb BVS between 1 and 2 years in patients with stable CAD and stabilized ACS was acceptable In particular, the scaffold thrombosis rate between 1 and 2 years was only 0.3% (NNH=317) for Absorb The cumulative 2-year TLF rates were higher with Absorb than Xience (11.0% vs 7.9%, p=0.03), but in patients with appropriately sized vessels the difference was smaller (9.4% vs 7.0%, p=0.11) Longer-term data from the ABSORB III/IV program will determine whether better patient selection and technique improve short-term outcomes, and whether Absorb improves late outcomes compared to Xience

35 Impact of Implantation Technique Implantation technique for Absorb BVS has evolved in recent years A growing body of evidence from ABSORB randomized trials and registries suggest that optimized implantation techniques may improve clinical outcomes Analysis based on pooled Absorb data was conducted to evaluate the impact of PSP, which stands for pre-dilatation, appropriate vessel sizing, and high pressure post-dilatation Pooled ABSORB data at 2 years: ABSORB EXTEND, ABSORB II, ABSORB Japan, ABSORB China, and ABSORB III

36 PSP Analysis Definition of PSP components (must satisfy all the criteria below) Pre-dilatation (performed in 99.9% of Absorb patients) Sizing (vessel): 2.25mm QCA RVD 3.5mm Post-dilatation: Pressure 18 atm Balloon diameter: Scaffold diameter > 1:1 and Balloon diameter Scaffold diameter + 0.5mm Full PSP: All three criteria met Not full PSP: any criteria not met

37 PSP Analysis Pooled ABSORB Trials Absorb Arm 1 Implantation Technique Absorb (N=2870) Pre-dilatation 99.9% 2.25 mm QCA RVD 3.5 MM 79.3% High pressure Post-dilatation % Full PSP %

38 Impact of Implantation Technique on Clinical Outcomes from 0 to 1 Year - Pooled ABSORB Trials Absorb Arm 1 Events (%) from 0 to 1 Year QCA RVD 2.25 mm to 3.5 mm P= TLF 5.0 P= ST (Def/Prob) 5.8 High Pressure Post-dilatation 2 Full PSP 3 TLF ST (Def/Prob) 6.0 TLF ST (Def/Prob) No (N=590) Yes (N=2261) No (N=2493) Yes (N=365) No (N=2559) Yes (N=298)

39 Impact of Implantation Technique on Clinical Outcomes from 1 to 2 Years - Pooled ABSORB Trials Absorb Arm 1 Events (%) from 1 to 2 Years QCA RVD 2.25 mm to 3.5 mm 4.0 TLF ST (Def/Prob) 3.5 High Pressure Post-dilatation 2 P=0.03 TLF ST (Def/Prob) P= TLF Full PSP ST (Def/Prob) No (N=590) Yes (N=2261) No (N=2493) Yes (N=365) No (N=2559) Yes (N=298)

40 Impact of Implantation Technique on Clinical Outcomes from 0 to 2 Years - Pooled ABSORB Trials Absorb Arm 1 Events (%) from 0 to 2 Years QCA RVD 2.25 mm to 3.5 mm P= TLF ST (Def/Prob) 8.9 High Pressure Post-dilatation 2 TLF ST (Def/Prob) P= TLF Full PSP ST (Def/Prob) No (N=590) Yes (N=2261) No (N=2493) Yes (N=365) No (N=2559) Yes (N=298)

41 TLF by 2 Years Pooled ABSORB Trials Absorb Arm 1 15% 12% Not Full PSP Full PSP 3 Sizing: 2.25 mm QCA RVD 3.5 mm Post-Dil: High Pressure Post-Dilatation 2 TLF Rate (%) by 2 Years 9% 6% 9.0% 7.6% 6.6% 5.4% 3% 0% No. at Risk: Not Full PSP Sizing Post-dil d l Full PSP Months Post Index Procedure

42 Scaffold Thrombosis (Def/Prob) by 2 Years Pooled ABSORB Trials Absorb Arm 1 5% 4% Not Full PSP Full PSP mm QCA RVD 3.5 mm High Pressure Post-Dilatation 2 ST Rate (%) by 2 Years 3% 2% 1.9% 1.5% 1% 0.8% 0.7% 0% No. at Risk: Not Full PSP Sizing Post-dil d l Full PSP Months Post Index Procedure

43 Events through 2 years (%) Impact of Full PSP * on Clinical Outcomes by 2 Years Pooled ABSORB Trials As-Treated Population ** 5.5 TLF 6.4 Absorb Not Full PSP (N=2559 [90%]) Absorb Full PSP (N=298 [10%]) All Xience (N=1277) ST (Def/Prob)

44 Blinded, Pooled, Interim ABSORB IV Outcomes: Comparison to ABSORB III ABSORB III: 2008 pts randomized 2:1 BVS:EES (1322:686) ABSORB IV: 3000 pts being randomized 1:1 BVS:EES ABSORB III Pooled (N=2008) 1 ABSORB IV Pooled (N=2546) 2,3 QCA RVD < 2.25 mm 19% 4% Post-dilatation (BVS) 66% 84% Pooled Stent/Scaffold Thrombosis 30 days 0.9% 0.4% 1 year 1.1% 0.5% 1. Assuming the observed event rates for each arm in ABSORB III, but adjusted for the 1:1 randomization ratio in ABSORB IV. The actual observed pooled ST rates in ABSORB III were 1.0% at 30 days and 1.3% at 1 year. 2. Based on February 15, 2017 data cut (N=2397 with 30-day FU and N=1415 with 1-year FU). 3. ABSORB IV includes ~25% non A-III like subjects (troponin+ ACS, 3 lesions treated, and planned staged procedures).

45 Conclusions In an era where technique was not strongly considered, there were small differences between Absorb and Xience However the principle of PSP, in particular proper vessel sizing and high pressure post-dilatation, may minimize two year differences between Absorb and Xience New insights regarding the impact of optimal technique on the early and late outcomes of Absorb BVS may emerge with the final 3-year data from ABSORB III, China and Japan, and when the ABSORB IV results become available

46 Prolonged DAPT OSPEDALE SAN RAFFAELE Previously, 1 year DAPT is considered as standard after BVS in most of lesions 3 years outcomes of ABSORB 2 reported 6 VLST in patients without DAPT Until a definitive answer comes out, prolonged DAPT seems appropriate PW Serruys et al. Lancet 2016;388(10059) / presented at TCT2016

47 FDA Warning - March 18, 2017 Absorb GT1 Bioresorbable Vascular Scaffold (BVS) by Abbott Vascular: Letter to Health Care Providers - FDA Investigating Increased Rate of Major Adverse Cardiac Events

48 Future Innovations Bioabsorbable polymers Drug eluting stents? 2nd Generation BVS Shorter generation dual antiplatelet therapy? Drug coated balloons Intravascular imaging and hemodynamic assessment Structural heart disease

49 References SCAI -Timeline: 30 years of progress in interventional cardiology Abbott Vascular - Absorb ABSORB III ABSORB IV id=

50 Thank You The legacy of an operator is measured by the scarcity of complications yet the absence of complications is a measure of the scarcity of operations.

51 Questions