Scaffolds: Results from the Randomized ABSORB III Trial Stephen G. - PowerPoint PPT Presentation

Three-Year Clinical Outcomes with Everolimus-Eluting Bioresorbable Scaffolds: Results from the Randomized ABSORB III Trial Stephen G. Ellis MD Dean J. Kereiakes MD and Gregg W. Stone MD for the ABSORB III Investigators NCT01751906

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company • • Consultant and research funding Abbott Vascular, Boston Scientific, Medtronic The ABSORB III study is solely funded by Abbott Vascular

Background • The Absorb everolimus-eluting PLLA-based BVS provides early drug delivery and mechanical support functions similar to metallic DES, followed by complete bioresorption with recovery of vascular structure and function • The ABSORB III trial demonstrated non-inferior rates of TLF (cardiac death, TVMI or ID-TLR) at 1 year in 2,008 patients with CAD randomized 2:1 to the Absorb BVS vs. Xience CoCr-EES • Clinical outcomes through 3 years, the approximate time of complete scaffold bioresorption, has not previously been reported from the ABSORB III trial

ABSORB III 2,250 pts with up to 2 de novo lesions in different epicardial vessels enrolled, with follow-up for 7-10 years, at up to 200 US and non-US sites 2,008 pts randomized 2:1 Absorb vs. Xience (+50 lead-in pts and 200 pt non-randomized angio/IVUS/OCT/VM FU cohort) RVD: 2.50 - 3.75 mm; Lesion length: ≤24 mm Scaffold diameters: 2.5, 3.0 and 3.5 mm Scaffold lengths: 12, 18, and 28 mm Follow-up: 30 days, 6 months, then yearly through 7-10 years (blinded after year 3) Primary endpoints: TLF at 1 year (non-inferiority) TLF between 3 and 7-10 years (pooled with ABSORB IV for superiority) PIs: SG Ellis, DJ Kereiakes Study chairman: GW Stone

Key Patient Eligibility Criteria • >18 years old • Evidence of myocardial ischemia (stable/unstable/post- infarction angina or silent ischemia) • No elevation of CK-MB • 1 or 2 de novo target lesions in up to 2 native coronary arteries (max 1 lesion per artery) • Diameter stenosis ≥50% and <100% with TIMI flow ≥1  If <70%, abnormal functional test (including FFR ≤0.80), unstable angina or post-infarct angina • RVD ≥2.50 mm and ≤3.75 mm (site -determined) • Lesion length ≤24 mm (site -determined)

Baseline Characteristics Absorb Xience ( N=1322) (N=686) (L=1385) (L=713) p-value Patient Characteristics Age (mean) 63.5 ±10.6 63.6±10.3 0.75 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 ± 5.4 13.1 ± 5.8 0.048 RVD, mm 2.67 ± 0.45 2.65 ± 0.46 0.36 DAPT Usage DAPT at 1 year 89.9% 90.4% 0.71 DAPT at 3 years 55.8% 53.5% 0.32 There were no major inter-group differences between baseline patient and lesion characteristics Ellis SG et al. N Engl J Med 2015;373:1905-15

Study Flow and Follow-up Randomized 2:1 N=2008 (ITT) ABSORB Xience N=1322 N=686 N=4 lost to follow-up N=6 lost to follow-up N=6 withdrew consent N=3 withdrew consent ABSORB Xience 1-Year Follow-up N=1312 N=677 99.2% Complete 98.7% Complete N=10 lost to follow-up N=4 lost to follow-up N=6 withdrew consent N=2 withdrew consent ABSORB Xience 2-Year Follow-up N=1296 N=671 98.0% Complete 97.8% Complete N=14 lost to follow-up N=8 lost to follow-up N=2 withdrew consent N=1 withdrew consent N=3 withdrawn by physician/site N=1 withdrawn by physician/site N=1 other ABSORB Xience 3-Year Follow-up N=1276 N=661 96.5% Complete 96.4% Complete

Target Lesion Failure 30% Absorb XIENCE Target lesion failure (%) 25% HR [95% CI] = 1.31 [0.99, 1.73] p = 0.056 20% 15% 13.4% 11.0% 10.4% 10% 7.8% 8.1% 5% 6.2% 0% 0 6 12 18 24 30 36 42 Time Post Procedure (Months) No. at Risk: Absorb 1322 1189 1135 1074 Xience 686 630 604 577 The 3-year window includes follow-up through 37 months

Target Lesion Failure: Landmark Analysis 0 – 1 Year 1 – 3 Years HR [95% CI] = HR [95% CI] = 1.33 [0.92, 1.92] 1.18 [0.81, 1.72] 30% Target lesion failure (%) p=0.13 p=0.39 25% Absorb 20% XIENCE 15% 10% 7.0% 7.5% 5.7% 6.0% 4.1% 5% 3.2% 0% 0 6 12 18 24 30 36 42 Time Post Procedure (Months) No. at Risk: Absorb 1322 1200 1215 1145 Xience 686 636 635 603

Device Thrombosis 5% Absorb XIENCE Device thrombosis (%) 4% HR [95% CI] = 3.12 [1.21, 8.05] p = 0.01 3% 2.3% 2% 1.8% 1.5% 1% 0.7% 0.7% 0.7% 0% 0 6 12 18 24 30 36 42 Time Post Procedure (Months) No. at Risk: Absorb 1322 1264 1242 1197 Xience 686 665 647 630 The 3-year window includes follow-up through 37 months

Device Thrombosis: Landmark Analysis 0 – 1 Year HR [95% CI] = 1 – 3 Years 5% 2.08 [0.78, 5.55] p=0.02 Device thrombosis (%) p=0.13 4% Absorb XIENCE 3% 2% 1.5% 1% 0.8% 0.7% 0.3% 0.0% 0.0% 0% 0 6 12 18 24 30 36 42 Time Post Procedure (Months) No. at Risk: Absorb 1322 1273 1256 1211 Xience 686 668 651 634

3-Year Clinical Events Absorb XIENCE HR (95%CI) P value (N=1322) (N=686) TLF 13.4% (174) 10.4% (70) 1.31 [0.99, 1.73] 0.056 - Cardiac death 1.4% (18) 1.2% (8) 1.17 [0.51, 2.69] 0.71 - TV-MI 8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] 0.03 - ID-TLR 7.2% (92) 5.9% (39) 1.23 [0.85, 1.79] 0.27 Stent thrombosis 2.3% (30) 0.7% (5) 3.12 [1.21, 8.05] 0.01 - Definite 2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] 0.02 - Probable 0.2% (2) 0.0% (0) - 0.31 Note: The 3-year window includes follow-up through 37 months

3-Year Clinical Events Absorb XIENCE HR (95%CI) P value (N=1322) (N=686) All Death 3.1% (40) 3.4% (23) 0.90 [0.54, 1.51] 0.70 - Cardiac Death 1.4% (18) 1.2% (8) 1.17 [0.51, 2.69] 0.71 All MI 10.2% (132) 7.6% (51) 1.36 [0.98, 1.88] 0.061 - TV-MI 8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] 0.03 - Related to 1.9% (25) 0.6% (4) 3.26 [1.13, 9.35] 0.02 device thrombosis - Unrelated to 6.8% (88) 5.3% (36) 1.28 [0.87, 1.88] 0.21 device thrombosis Note: The 3-year window includes follow-up through 37 months

3-Year Clinical Events Absorb XIENCE HR (95%CI) P value (N=1322) (N=686) All revascularization 16.4% (210) 12.7% (85) 1.31 [1.02, 1.68] 0.04 - ID-TVR 11.6% (148) 7.7% (51) 1.54 [1.12, 2.11] 0.01 - All TLR 7.3% (93) 5.9% (39) 1.25 [0.86, 1.81] 0.25 - ID-TLR 7.2% (92) 5.9% (39) 1.23 [0.85, 1.79] 0.27 - Related to 2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] 0.02 device thrombosis - Unrelated to 5.2% (66) 5.2% (34) 1.01 [0.67, 1.53] 0.96 device thrombosis Note: The 3-year window includes follow-up through 37 months

Target Lesion Failure: Stratified by Vessel Size RVD ≥2.25 mm RVD <2.25 mm HR [95% CI] = 1.49 [0.88, 2.52] HR [95% CI] = 1.26 [0.91, 1.75] 30% 30% p = 0.14 p = 0.16 Target lesion failure (%) 25% 25% Absorb Absorb XIENCE XIENCE 20.9% 18.4% 20% 20% 14.9% 15% 12.9% 15% 11.6% 11.8% 9.4% 10% 10% 9.4% 8.3% 6.6% 7.3% 5% 5% 5.7% 0% 0% 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Time Post Procedure (Months) Time Post Procedure (Months) No. at Risk: 1074 979 938 888 Absorb 242 193 182 206 549 493 474 109 509 Xience 133 119 101

Device Thrombosis: Stratified by Vessel Size RVD ≥2.25 mm RVD <2.25 mm HR [95% CI] = 3.34 [0.75, 14.91] HR [95% CI] = 3.08 [0.91, 10.47] 10% p = 0.09 10% p = 0.06 Device thrombosis %) Absorb Absorb 8% 8% XIENCE XIENCE 6% 6% 5.0% 4.6% 4.6% 4% 4% 2% 2% 1.5% 1.5% 1.7% 1.5% 1.2% 0.8% 0.5% 0.5% 0.5% 0% 0% 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Time Post Procedure (Months) Time Post Procedure (Months) No. at Risk: 1074 1036 1016 977 Absorb 242 222 216 224 549 535 525 514 120 Xience 133 128 114

Device Thrombosis: Landmark Analysis Stratified by Vessel Size RVD ≥2.25 mm RVD <2.25 mm 0 – 1 Year 1 – 3 Years 0 – 1 Year 1 – 3 Years 10% 10% HR [95% CI] = HR [95% CI] = p=0.47 p=0.03 3.07 [0.68,13.85] 1.53 [0.42,5.67] Device thrombosis %) p=0.12 p=0.52 8% 8% Absorb Absorb XIENCE XIENCE 6% 6% 4.6% 4% 4% 2% 2% 0.8% 1.5% 0.9% 0.4% 0.5% 0.0% 0.0% 0% 0% 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Time Post Procedure (Months) Time Post Procedure (Months) No. at Risk: 1074 1044 1023 984 Absorb 242 229 223 224 549 537 528 517 121 Xience 133 129 115