Three-Year Clinical Outcomes with Everolimus-Eluting Bioresorbable Scaffolds: Results from the Randomized ABSORB III Trial Stephen G.

Transcription

1 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 NCT

2 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

3 Background The 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 BVS vs. CoCr-EES Clinical outcomes through 3 years, the approximate time of complete scaffold bioresorption, has not previously been reported from the ABSORB III trial

4 PIs: SG Ellis, DJ Kereiakes Study chairman: GW Stone 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 vs. (+50 lead-in pts and 200 pt non-randomized angio/ivus/oct/vm FU cohort) RVD: 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)

5 Key Patient Eligibility Criteria >18 years old Evidence of myocardial ischemia (stable/unstable/postinfarction 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)

6 Patient Characteristics (N=1322) (L=1385) (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 Baseline Characteristics 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:

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lost to follow-up N=2 withdrew consent 98.0% Complete 97.8% Complete N=14 lost to follow-up N=2 withdrew consent N=3 withdrawn by physician/site N=1 other 3-Year Follow-up N=8 lost to follow-up N=1 withdrew consent N=1 withdrawn by physician/site 96.5% Complete 96.4% Complete N=677 N=671 N=661

8 Target lesion failure (%) Target Lesion Failure 30% 25% 20% HR [95% CI] = 1.31 [0.99, 1.73] p = % 10% 7.8% 11.0% 13.4% 10.4% 5% 6.2% 8.1% No. at Risk: 0% Time Post Procedure (Months) The 3-year window includes follow-up through 37 months

9 Target lesion failure (%) Target Lesion Failure: Landmark Analysis 30% 25% 20% 0 1 Year 1 3 Years HR [95% CI] = 1.33 [0.92, 1.92] p=0.13 HR [95% CI] = 1.18 [0.81, 1.72] p= % 10% 5% 7.5% 5.7% 4.1% 7.0% 6.0% No. at Risk: 0% Time Post Procedure (Months) %

10 Device thrombosis (%) Device Thrombosis 5% 4% 3% HR [95% CI] = 3.12 [1.21, 8.05] p = % 1.5% 1.8% 2.3% 1% 0.7% 0.7% 0.7% No. at Risk: 0% Time Post Procedure (Months) The 3-year window includes follow-up through 37 months

11 Device thrombosis (%) Device Thrombosis: Landmark Analysis 5% 4% 0 1 Year HR [95% CI] = 2.08 [0.78, 5.55] p= Years p=0.02 3% No. at Risk: 2% 1% 0% 1.5% 0.7% 0.3% 0.0% 0.8% 0.0% Time Post Procedure (Months)

12 3-Year Clinical Events (N=1322) (N=686) HR (95%CI) P value TLF 13.4% (174) 10.4% (70) 1.31 [0.99, 1.73] Cardiac death 1.4% (18) 1.2% (8) 1.17 [0.51, 2.69] TV-MI 8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] 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] Definite 2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] Probable 0.2% (2) 0.0% (0) Note: The 3-year window includes follow-up through 37 months

13 3-Year Clinical Events (N=1322) (N=686) HR (95%CI) P value All Death 3.1% (40) 3.4% (23) 0.90 [0.54, 1.51] 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] TV-MI 8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] Related to device thrombosis - Unrelated to device thrombosis 1.9% (25) 0.6% (4) 3.26 [1.13, 9.35] % (88) 5.3% (36) 1.28 [0.87, 1.88] 0.21 Note: The 3-year window includes follow-up through 37 months

14 3-Year Clinical Events (N=1322) (N=686) HR (95%CI) P value All revascularization 16.4% (210) 12.7% (85) 1.31 [1.02, 1.68] ID-TVR 11.6% (148) 7.7% (51) 1.54 [1.12, 2.11] All TLR 7.3% (93) 5.9% (39) 1.25 [0.86, 1.81] ID-TLR 7.2% (92) 5.9% (39) 1.23 [0.85, 1.79] Related to device thrombosis - Unrelated to device thrombosis 2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] % (66) 5.2% (34) 1.01 [0.67, 1.53] 0.96 Note: The 3-year window includes follow-up through 37 months

15 Target lesion failure (%) Target Lesion Failure: Stratified by Vessel Size 30% RVD <2.25 mm HR [95% CI] = 1.49 [0.88, 2.52] p = % RVD 2.25 mm HR [95% CI] = 1.26 [0.91, 1.75] p = % 20% 18.4% 20.9% 25% 20% 15% 10% 5% 12.9% 8.3% 11.6% 14.9% 15% 10% 5% 6.6% 5.7% 9.4% 7.3% 11.8% 9.4% No. at Risk: 0% Time Post Procedure (Months) % Time Post Procedure (Months)

16 Device thrombosis %) Device Thrombosis: Stratified by Vessel Size 10% RVD <2.25 mm HR [95% CI] = 3.34 [0.75, 14.91] p = % RVD 2.25 mm HR [95% CI] = 3.08 [0.91, 10.47] p = % 8% 6% 4.6% 4.6% 5.0% 6% 4% 4% No. at Risk: 2% 0% % Time Post Procedure (Months) % % 2% 0% % 0.5% Time Post Procedure (Months) % 0.5% % 0.5%

17 Device thrombosis %) Device Thrombosis: Landmark Analysis Stratified by Vessel Size RVD <2.25 mm RVD 2.25 mm 10% 8% 0 1 Year HR [95% CI] = 3.07 [0.68,13.85] p= Years p= % 8% 0 1 Year HR [95% CI] = 1.53 [0.42,5.67] p= Years p=0.03 6% 6% 4% 4.6% 4% No. at Risk: 2% 0% 1.5% 0.4% 0.0% Time Post Procedure (Months) % 0% 0.8% 0.5% 0.9% 0.0% Time Post Procedure (Months)

18 Multivariable Predictors: 0 3 Years Outcome Variable Relative Risk [95% CI] P TLF Pre-procedure RVD <2.25 mm* 1.72 [1.28, 2.32] Prior coronary intervention 1.37 [1.04, 1.81] Scaffold thrombosis Pre-procedure RVD <2.25 mm* 2.80 [1.37, 5.71] Diabetes mellitus 2.77 [1.36, 5.64] *By QCA Variables entered into the TLF multiple model: ACC/AHA lesion class, age (median 64 years), treatment arm, calcification (moderate/severe), prior cardiac interventions, any diabetes, hypercholesterolemia requiring medication, sex, hypertension requiring medication, presentation (unstable angina and recent MI vs. stable ischemic syndrome), bifurcation, target vessel: LAD, target lesion length (mm, median), prior cardiac intervention, pre-procedure MLD (mm, median), number of target lesions, P2Y12 receptor antagonist (loading), pre-procedural RVD (<2.25 mm vs mm), current tobacco use. Variables entered into the ST multiple model: ACC/AHA lesion class, treatment arm, Any diabetes, presentation (unstable angina and recent MI vs. stable ischemic syndrome), target lesion length (mm, median), pre-procedural RVD (<2.25 mm vs mm).

19 Multivariable Predictors: 0 3 Years Outcome Variable Relative Risk [95% CI] P Prior coronary intervention 2.45 [1.56, 3.85] < TLF Diabetes mellitus 1.59 [1.03, 2.47] 0.03 LAD target vessel 1.74 [1.12, 2.72] 0.01 There were no independent predictors of stent thrombosis. Variables entered into the TLF logistic model: ACC/AHA lesion class, age (median 64 years), treatment arm, calcification (moderate/severe), prior cardiac interventions, any diabetes, hypercholesterolemia requiring medication, sex, hypertension requiring medication, presentation (unstable angina and recent MI vs. stable ischemic syndrome), bifurcation, target vessel: LAD, target lesion length (mm, median), prior cardiac intervention, pre-procedure MLD (mm, median), number of target lesions, P2Y12 receptor antagonist (loading), pre-procedural RVD (<2.25 mm vs mm), current tobacco use.

20 Limitations ABSORB III enrolled patients with stable ischemic heart disease and stabilized ACS, and excluded complex lesions 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 - Detailed analysis of the impact of PSP on outcomes will be presented in the Featured Clinical Research session Tuesday 10/31 at 12:45 pm in Mile High Ballroom 1A-1B

21 Summary and Conclusions In the large-scale ABSORB III trial, device-related clinical events (TLF) continued to accrue between 1 and 3 years following PCI with both BVS and EES, although to a slightly greater extent with BVS Three-year rates of composite adverse events were increased with BVS compared to EES, driven by greater rates of scaffold thrombosis and TVMI Longer-term clinical follow-up is necessary to determine whether more normal coronary structure and function after complete scaffold bioresorption will result in a favorable late net safety and efficacy profile of BVS compared to permanent metallic DES

22 ABSORB III 3-Year Publication JACC 2017:on-line