Bernard Chevalier Institut Jacques Cartier, Massy, France. Patrick W. Serruys Imperial College, London, UK Erasmus University MC, Netherlands

Transcription

1 The 4-year Clinical Outcomes of the ABSORB II Trial: First Randomized Comparison between the Absorb Everolimus Eluting Bioresorbable Vascular Scaffold and the Everolimus Eluting Stent Bernard Chevalier Institut Jacques Cartier, Massy, France Patrick W. Serruys Imperial College, London, UK Erasmus University MC, Netherlands on behalf of the ABSORB II Investigators

2 Presentor Disclosures Bernard Chevalier was a Consultant for Abbott Vascular and is currently consultant for Biotronik, Colibri, Cordis, Medtronic, Terumo. Patrick Serruys is a Member of the International Advisory Board of Abbott Vascular

3 ABSORB II Study Design 501 subjects Randomized 2:1 Absorb BVS: / 46 sites (Europe and New Zealand) Clinical Follow-Up 30d QoL follow-up Angio, IVUS follow-up MSCT follow-up (Absorb arm only)* 6m 12m 24m 36m 48m 60m Study Objective Co-primary Endpoints 36 months Treatment Device Sizes Randomized against control. First Patient In: 28-Nov-2011 Vasomotion assessed by change in Mean Lumen Diameter between preand post-nitrate at 3 years (superiority) Minimum Lumen Diameter (MLD) at 3 years post nitrate minus MLD post procedure post nitrate (non-inferiority, reflex to superiority) Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions 48 mm Device diameters: 2.5, 3.0, 3.5 mm Device lengths: 12 (3.5 mm diameter only), 18, 28 mm The ABSORB II study is sponsored by Abbott Vascular. [NCT ]

4 Characteristics of Patients at Baseline Absorb 335 pts Xience 166 pts 95% CI Age (year) mean ±SD 61.5 ± ± 10.0 N.S. Male % N.S. Current Tobacco Use % N.S. Hypertension % N.S. Dyslipidemia % N.S. All Diabetes Mellitus % N.S. Diabetes Mellitus Insulin Dependent % N.S. Family History of Premature CAD % N.S. Prior Intervention in Target Vessel % N.S. Prior MI % N.S. Stable Angina % N.S. Unstable Angina % N.S. Silent Ischemia % N.S. Recent MI with normalized cardiac enzyme % N.S.

5 Procedural Assessment Pre and Post Procedure Absorb 364 Lesions Xience 182 Lesions p value Procedural Details Per Lesion Balloon dilatation prior to device implantation % Planned overlap with the same type of device % Unplanned/bailout implantation same % Nominal size of study device mm Balloon dilatation after device implantation % Nominal diameter of last balloon used mm Maximum last balloon pressure used atm Acute recoil post device implantation mm < < Acute Clinical Device Success % Acute Clinical Procedural Success %

6 7 withdrawal 4 death 3 withdrawal 1 LFU 4-Year Patient Flowchart Absorb BVS N=335 Intent To Treat N=501 Baseline N=166 N=328 1-year N= * and 154** patients still in the study but 5 missed 3 yr FUP 1 death 2 withdrawal 3 withdrawal 4 death 3 withdrawal 2 LFU, 3 MV, 2 death, 8 MV, 3 withdrawal 9 no consent, -3 still in study but missed 3yr FUP N=320 2-year N=160 N=308* N=289 (86%) 3-year 4-year N=152** N=139 (84%) 5 death, 1 LFU 2 MV At 4 years patients with missing visits (MV) were confirmed as alive and well by site PI. 20 patients did not sign protocol amendment for 4 & 5 year follow-up 1 death, 2 MV, 1 withdrawal 11 no consent,-2 still in study but missed 3yr FUP

7 Clinical Endpoints at 3 Years Hierarchical Absorb 325 patients Xience 161 patients Relative Risk p value Device-oriented composite endpoint [DOCE] 10.5% 5.0% 2 11 [1 00, 4 44] 0 04 Cardiac death 0.9% 1.9% 0 50 [0 10, 2 43] 0 4 Target vessel MI 6.5% (21) 1.2% (2) 5 20 [1 23, 21 91] 0 01 Periprocedural MI* 4.0%(13) 1.2% (2) 3.22 [0.74, 14.10] 0.16 Spontaneous MI* 2.5% (8) 0% (0) NC [NC] 0.06 Clinically indicated TLR 3.1% (10) 1.9% (3) 1 65 [0 46, 5 92] 0 56 Patient-oriented composite endpoint [POCE] 20.9% 24.2% 0 86 [0 61, 1 22] 0 4 All-cause death 2.5% 3.7% 0 66 [0 23, 1 87] 0 57 Any MI 7.7% 3.1% 2.48 [0.97, 6.35] Any revascularization 10.8% 17.4% 0 62 [0 39, 0 98] 0.04 * Per extend historical MI definition

8 TLF per WHO (%) Device oriented Composite Endpoint (DOCE)/ Target Lesion Failure (TLF) BVS HR [95% CI]= 2.17 [1.01,4.69] p=0.043 (Log rank test) % 5 4.9% Time Post Index Procedure (Days) DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)

9 TLF per WHO (%) Device oriented Composite Endpoint (DOCE)/ Target Lesion Failure (TLF) BVS HR [95% CI]= 2.04 [0.98,4.24] p=0.050 (Log rank test) HR [95% CI]= 1.44 [0.15,13.80] p=0.75 (Log rank test) Δ = 0.3% % 1.0% 0.7% 5 5.6% Time Post Index Procedure (Days) DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)

10 POCE / DMR per WHO (%) Patient oriented Composite Endpoint (PoCE)/DMR 30 BVS HR [95% CI]= 0.85 [0.58,1.27] 24.2% 25 p=0.43 (Log rank test) % Time Post Index Procedure (Days) PoCE=DMR: All Death, all Myocardial infarction, and all Revascularisation

11 POCE / DMR per WHO (%) Patient oriented Composite Endpoint (PoCE)/DMR BVS HR [95% CI]= 0.90 [0.61,1.33] p=0.60 (Log rank test) 24.9% 22.9% HR [95% CI]= 3.14 [0.71,13.93] p=0.11 (Log rank test) Δ = 2.9% 4.3% 1.4% Time Post Index Procedure (Days) PoCE=DMR: All Death, all Myocardial infarction, and all Revascularisation

12 4-year Clinical Outcomes Composite Endpoints Absorb BVS N=335 N=166 p value PoCE (%) MACE (%) DoCE, TLF (%) TVF (%) PoCE (Patient oriented Composite Endpoint): All death, all myocardial infarction, and all revascularisation MACE (Major Adverse Cardiac Events): Cardiac death, all myocardial infarction, and clinically indicated target-lesion revascularisation (TLR) DoCE (Device oriented Composite Endpoint)/ TLF (Target Lesion Failure): Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR) TVF (Target Vessel Failure): Cardiac death, all myocardial infarction, clinically indicated target-vessel revascularisation (TVR)

13 Clinical Outcomes Non Hierarchical Events Absorb BVS N= years N=166 p value Death* n(%) 2(0.7) 1(0.7) Cardiac 1(0.3) 1(0.7) Vascular 0(0.0) 0(0.0) Non-cardiovascular 1(0.3) 0(0.0) Myocardial Infarction n(%) 1(0.3) 0(0.0) Q-wave 0(0.0) 0(0.0) Non Q-wave 1(0.3) 0(0.0) All Revascularization* n(%) 10(3.3) 1(0.7) All TLR 2(0.7) 0(0.0) All NTL-TVR 4(1.3) 0(0.0) All NTVR 6(2.0) 1(0.7) *Per ARC. Cutlip et al., Circulation. 2007;115:

14 ARCST DPr (%) Definite/Probable Scaffold/Stent Thrombosis* 25 BVS HR [95% CI]= NA [NA] 20 p=0.033 (Log rank test) % 0.0% Time Post Index Procedure (Days) *Per ARC. Cutlip et al., Circulation. 2007;115:

15 ARCST DPr (%) Definite/Probable Scaffold/Stent Thrombosis* BVS HR [95% CI]= NA [NA] p=0.033 (Log rank test) 25 No stent/scaffold thrombosis between 3 and 4 years HR [95% CI]= NA [NA] p= (Log rank test) % 0.0% % 0.0% Time Post Index Procedure (Days) *Per ARC. Cutlip et al., Circulation. 2007;115:

16 Scaffold/Stent Thrombosis Absorb BVS N=335 4 years N=166 p value Definite ST* days (%) Acute/sub-acute (0-30 days Late ( days) Very late ( days) Very late between 3 4 year follow-up (N) 0 0 NA Definite/Probable ST* days(%) Acute/sub-acute (0-30 days) Late ( days) Very late ( days) Very late between 3 4 year follow-up (N) 0 0 NA *Per ARC. Cutlip et al., Circulation. 2007;115:

17 Post-Procedure Usage of Antiplatelet Medication through 4 years On Aspirin (%) On DAPT (%) Absorb BVS N=335 N=166 p value at 1 year at 4 years at 1 year at 2 years at 3 years at 4 years

18 4-year Summary Excluding Subjects with ST Absorb BVS N= 326 N= 166 p value Hierarchical PoCE*, % All death (Non-hierarchical) All MI (Non-hierarchical) All revascularization (Non-hierarchical) Hierarchical DoCE* or TLF, % Cardiac death (Non-hierarchical) TV-MI (Non-hierarchical) CI-TLR (Non-hierarchical) Per Protocol Myocardial Infarction (MI): Q wave MI Development of new, pathological Q wave on the ECG. Non-Q wave MI Elevation of CK levels to two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves. PoCE (Patient oriented Composite Endpoint)*: All death, all myocardial infarction, and all revascularisation. DoCE (Device oriented Composite Endpoint)*/ TLF (Target Lesion Failure): Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR). *Per ARC. Cutlip et al., Circulation. 2007;115:

19 4-year Summary of Subjects on DAPT at 4 Years Absorb BVS N= 86 N= 35 p value Hierarchical PoCE*, % All death (Non-hierarchical) All MI (Non-hierarchical) All revascularization (Non-hierarchical) Hierarchical DoCE* or TLF, % Cardiac death (Non-hierarchical) TV-MI (Non-hierarchical) CI-TLR (Non-hierarchical) Per Protocol Myocardial Infarction (MI): Q wave MI Development of new, pathological Q wave on the ECG. Non-Q wave MI Elevation of CK levels to two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves. PoCE (Patient oriented Composite Endpoint)*: All death, all myocardial infarction, and all revascularisation. DoCE (Device oriented Composite Endpoint)*/ TLF (Target Lesion Failure): Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR). *Per ARC. Cutlip et al., Circulation. 2007;115:

20 Limitations The ABSORB II study was not powered for clinical endpoints Patients in the ABSORB II Study were enrolled before the current recommendations for scaffold implantation

21 Conclusions The Absorb scaffold polymer has been reported to be completely bio-resorbed by 3 years. Between 3 and 4 years follow up there were no ST events in the Absorb arm DOCE/TLF events were similar between Absorb and Xience In a trial which was not powered for clinical events, at 4 years there were no statistically significant differences in the clinical outcomes between the two arms: PoCE (all death, all MI and all revascularization) Absorb BVS: 23.6% vs : 26.7%, p=0.47 DoCE/TLF (cardiac death, TV-MI and TLR) Absorb BVS: 11.5% vs : 6.0%, p=0.06 The exploratory observations presented in this report are hypothesis generating and need to be confirmed in larger randomized trials such as ABSORB III and ABSORB IV

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