The 4 year Clinical Outcomes of the ABSORB
The 4 -year Clinical Outcomes of the ABSORB II Trial: First Randomized Comparison between the Absorb Everolimus Eluting Bioresorbable Vascular Scaffold and the XIENCE 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
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
ABSORB II Study Design 501 subjects Randomized 2: 1 Absorb BVS: XIENCE / 46 sites (Europe and New Zealand) Clinical Follow-Up 30 d 6 m 12 m 24 m 36 m 48 m 60 m Qo. L follow-up Angio, IVUS follow-up MSCT follow-up (Absorb arm only)* Study Objective Randomized against XIENCE control. First Patient In: 28 -Nov-2011 Vasomotion assessed by change in Mean Lumen Diameter between pre- Co-primary Endpoints and post-nitrate at 3 years (superiority) 36 months Minimum Lumen Diameter (MLD) at 3 years post nitrate minus MLD post procedure post nitrate (non-inferiority, reflex to superiority) Treatment Device Sizes 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 01425281]
Characteristics of Patients at Baseline Absorb 335 pts Xience 166 pts 95% CI 61. 5 ± 10. 0 60. 9 ± 10. 0 N. S. Male % 75. 5 79. 5 N. S. Current Tobacco Use % 23. 6 21. 7 N. S. Hypertension % 69. 0 71. 7 N. S. Dyslipidemia % 75. 2 80. 1 N. S. All Diabetes Mellitus % 23. 9 24. 1 N. S. Diabetes Mellitus Insulin Dependent % 6. 6 8. 4 N. S. Family History of Premature CAD % 36. 6 41. 3 N. S. Prior Intervention in Target Vessel % 11. 7 8. 9 N. S. Prior MI % 28. 0 28. 9 N. S. Stable Angina % 63. 9 64. 5 N. S. Unstable Angina % 20. 3 22. 3 N. S. Silent Ischemia % 12. 5 11. 4 N. S. Recent MI with normalized cardiac enzyme % 3. 3 1. 8 N. S. Age (year) mean ±SD
Procedural Assessment Pre and Post Procedure p Absorb 364 Lesions Xience 182 Lesions value Procedural Details Per Lesion Balloon dilatation prior to device implantation % 100 98. 9 0. 11 Planned overlap with the same type of device % 15. 4 11. 0 0. 16 Unplanned/bailout implantation “same” % 3. 8 6. 0 0. 25 mm 3. 01 3. 05 0. 10 % 60. 7 58. 8 0. 67 mm 3. 08 3. 16 0. 02 15. 03 0. 01 0. 19 0. 85 Nominal size of study device Balloon dilatation after device implantation Nominal diameter of last balloon used Maximum last balloon pressure used Acute recoil post device implantation atm 14. 23 mm 0. 19 < < Acute Clinical Device Success % 99. 2 100 0. 55 Acute Clinical Procedural Success % 96. 1 98. 8 0. 16
4 -Year Patient Flowchart Intent To Treat N=501 Absorb BVS N=335 Baseline XIENCE N=166 1 death 2 withdrawal 7 withdrawal 4 death 3 withdrawal 1 LFU 4 death 3 withdrawal 2 LFU, 3 MV, 2 death, 8 MV, 3 withdrawal 9 no consent, -3 still in study but missed 3 yr FUP 311* and 154** patients still in the study but 5 missed 3 yr FUP N=328 1 -year N=163 3 withdrawal N=320 2 -year N=160 5 death, 1 LFU 2 MV N=308* N=289 (86%) 3 -year N=152** 4 -year N=139 1 death, 2 MV, 1 withdrawal 11 no consent , -2 still in study but missed 3 yr FUP (84%) 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
Clinical Endpoints at 3 Years Hierarchical Device-oriented composite endpoint [DOCE] Cardiac death Target vessel MI Periprocedural MI* Spontaneous MI* Clinically indicated TLR Patient-oriented composite endpoint [POCE] All-cause death Any MI Any revascularization * Per extend historical MI definition Absorb 325 patients Xience 161 patients Relative Risk p value 10. 5% 5. 0% 2· 11 [1· 00, 4· 44] 0· 04 0. 9% 6. 5% (21) 4. 0%(13) 2. 5% (8) 3. 1% (10) 1. 9% 1. 2% (2) 0% (0) 1. 9% (3) 0· 50 [0· 10, 2· 43] 0· 4 5· 20 [1· 23, 21· 91] 0· 01 3. 22 [0. 74, 14. 10] 0. 16 NC [NC] 0. 06 1· 65 [0· 46, 5· 92] 0· 56 20. 9% 24. 2% 0· 86 [0· 61, 1· 22] 0· 4 2. 5% 7. 7% 10. 8% 3. 7% 3. 1% 17. 4% 0· 66 [0· 23, 1· 87] 0· 57 2. 48 [0. 97, 6. 35] 0. 048 0· 62 [0· 39, 0· 98] 0. 04
Device oriented Composite Endpoint (DOCE)/ Target Lesion Failure (TLF) 25 BVS XIENCE HR [95% CI]= 2. 17 [1. 01, 4. 69] p=0. 043 (Log rank test) TLF per WHO (%) 20 15 10. 4% 10 4. 9% 5 0 0 180 360 540 720 900 1080 1260 1440 1620 Time Post Index Procedure (Days) Do. CE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)
Device oriented Composite Endpoint (DOCE)/ Target Lesion Failure (TLF) 25 BVS 25 XIENCE 15 p=0. 050 (Log rank test) 20 HR [95% CI]= 1. 44 [0. 15, 13. 80] p=0. 75 (Log rank test) 20 HR [95% CI]= 2. 04 [0. 98, 4. 24] TLF per WHO (%) 10 Δ = 0. 3% 5 15 0 1152 1260 1440 11. 1% 10 5. 6% 5 0 0 180 360 540 720 900 1080 1260 1440 1620 Time Post Index Procedure (Days) Do. CE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR) 1. 0% 0. 7% 1620
Patient oriented Composite Endpoint (Po. CE)/DMR POCE / DMR per WHO (%) 30 BVS XIENCE HR [95% CI]= 0. 85 [0. 58, 1. 27] 25 24. 2% p=0. 43 (Log rank test) 20 20. 9% 15 10 5 0 0 180 360 540 720 900 1080 1260 1440 Time Post Index Procedure (Days) Po. CE=DMR: All Death, all Myocardial infarction, and all Revascularisation 1620
Patient oriented Composite Endpoint (Po. CE)/DMR POCE / DMR per WHO (%) 30 BVS XIENCE 24. 9% HR [95% CI]= 0. 90 [0. 61, 1. 33] 25 p=0. 60 (Log rank test) 22. 9% 20 30 15 25 20 10 HR [95% CI]= 3. 14 [0. 71, 13. 93] p=0. 11 (Log rank test) 15 10 Δ = 2. 9% 5 4. 3% 1. 4% 5 0 1152 0 0 180 360 540 720 900 1080 1260 1440 Time Post Index Procedure (Days) Po. CE=DMR: All Death, all Myocardial infarction, and all Revascularisation 1440 1620
4 -year Clinical Outcomes Composite Endpoints Absorb BVS N=335 XIENCE N=166 p value Po. CE (%) 23. 6 26. 7 0. 4682 MACE (%) 12. 4 8. 0 0. 1545 Do. CE, TLF (%) 11. 5 6. 0 0. 0628 TVF (%) 14. 0 0. 9970 Po. CE (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) Do. CE (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)
Clinical Outcomes Non Hierarchical Events 3 -4 years Death* n(%) Cardiac Vascular Non-cardiovascular Myocardial Infarction n(%) Q-wave Non Q-wave All Revascularization* n(%) All TLR All NTL-TVR All NTVR Absorb BVS N=335 XIENCE N=166 p value 2(0. 7) 1(0. 3) 0(0. 0) 1(0. 3) 10(3. 3) 2(0. 7) 4(1. 3) 6(2. 0) 1(0. 7) 0(0. 0) 1(0. 7) 1. 0000 0. 5408 1. 0000 0. 1142 1. 0000 0. 3102 0. 4373 *Per ARC. Cutlip et al. , Circulation. 2007; 115: 2344 -2351
Definite/Probable Scaffold/Stent Thrombosis* 25 BVS XIENCE HR [95% CI]= NA [NA] p=0. 033 (Log rank test) ARCST DPr (%) 20 15 10 5 2. 8% 0. 0% 0 0 180 360 540 720 900 1080 1260 1440 Time Post Index Procedure (Days) *Per ARC. Cutlip et al. , Circulation. 2007; 115: 2344 -2351 1620
Definite/Probable Scaffold/Stent Thrombosis* 25 BVS XIENCE No stent/scaffold thrombosis between 3 and 4 years” HR [95% CI]= NA [NA] p=0. 033 (Log rank test) 20 25 ARCST DPr (%) 20 15 15 HR [95% CI]= NA [NA] p= (Log rank test) 10 5 10 0 1152 0. 0% 1260 1440 1620 5 2. 8% 0. 0% 0 0 180 360 540 720 900 1080 1260 Time Post Index Procedure (Days) *Per ARC. Cutlip et al. , Circulation. 2007; 115: 2344 -2351 1440 1620
Scaffold/Stent Thrombosis 4 years Definite ST* 0 -1488 days (%) Acute/sub-acute (0 -30 days Late (31 -365 days) Very late (365 – 14888 days) Very late between 3 – 4 year follow-up (N) Definite/Probable ST* 0 -1488 days(%) Acute/sub-acute (0 -30 days) Late (31 -365 days) Very late (365 – 1488 days) Very late between 3 – 4 year follow-up (N) Absorb BVS N=335 XIENCE N=166 p value 2. 6 0. 0 1. 8 0 3. 0 0. 6 0. 3 1. 8 0 0 0. 0583 1. 0000 0. 1851 NA 0. 0347 1. 0000 0. 1851 NA *Per ARC. Cutlip et al. , Circulation. 2007; 115: 2344 -2351
Post-Procedure Usage of Antiplatelet Medication through 4 years Absorb BVS N=335 XIENCE N=166 p value at 1 year at 4 years 95. 8 84. 4 95. 2 81. 3 0. 7473 0. 3794 at 1 year at 2 years at 3 years at 4 years 81. 0 28. 6 29. 8 25. 9 80. 7 28. 9 27. 7 21. 1 0. 9357 0. 9442 0. 6254 0. 2372 On Aspirin (%) On DAPT (%)
4 -year Summary Excluding Subjects with ST Hierarchical Po. CE*, % All death (Non-hierarchical) All MI (Non-hierarchical) All revascularization (Non-hierarchical) Hierarchical Do. CE* or TLF, % Cardiac death (Non-hierarchical) TV-MI (Non-hierarchical) CI-TLR (Non-hierarchical) Absorb BVS N= 326 XIENCE N= 166 p value 21. 3 3. 0 5. 9 15. 1 26. 7 4. 7 3. 3 22. 7 0. 2025 0. 3503 0. 2398 0. 0457 8. 9 6. 0 0. 2893 1. 0 4. 6 3. 9 2. 7 1. 3 2. 0 0. 2254 0. 0762 0. 4042 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. Po. CE (Patient oriented Composite Endpoint)*: All death, all myocardial infarction, and all revascularisation. Do. CE (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: 2344 -2351
4 -year Summary of Subjects on DAPT at 4 Years Hierarchical Po. CE*, % All death (Non-hierarchical) All MI (Non-hierarchical) All revascularization (Non-hierarchical) Hierarchical Do. CE* or TLF, % Cardiac death (Non-hierarchical) TV-MI (Non-hierarchical) CI-TLR (Non-hierarchical) Absorb BVS N= 86 XIENCE N= 35 p value 37. 2 0. 0 10. 5 33. 7 42. 9 0. 0 5. 7 42. 9 0. 5633 1. 0000 0. 5076 0. 3435 17. 4 5. 7 0. 1472 0. 0 10. 5 12. 8 0. 0 5. 7 1. 0000 0. 0578 0. 3429 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. Po. CE (Patient oriented Composite Endpoint)*: All death, all myocardial infarction, and all revascularisation. Do. CE (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: 2344 -2351
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
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: – Po. CE (all death, all MI and all revascularization) Absorb BVS: 23. 6% vs XIENCE: 26. 7%, p=0. 47 – Do. CE/TLF (cardiac death, TV-MI and TLR) Absorb BVS: 11. 5% vs XIENCE: 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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