The 2-year Clinical Outcomes of the ABSORB II Trial: First - - PowerPoint PPT Presentation

The 2-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

• n behalf of the ABSORB II Investigators

12 October 2015 - San Francisco, CA - U.S.A Plenary Session VII. First Report Investigations 1. 12:00pm

Presentor Disclosures

Bernard Chevalier is a consultant for Abbott Vascular Patrick Serruys is a member of the international advisory board of Abbott Vascular

ABSORB II Study Design

Study Objective Randomized against XIENCE control. First Patient In: 28-Nov-2011 Co-primary Endpoints 36 months Vasomotion assessed by change in Mean Lumen Diameter between pre- and 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) Treatment Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions ≤ 48 mm Device Sizes Device diameters: 2.5, 3.0, 3.5 mm Device lengths: 12 (3.5 mm diameter only), 18, 28 mm

501 subjects

Randomized 2:1 Absorb BVS:XIENCE / 46 sites (Europe and New Zealand) Clinical Follow-Up 24m 6m 12m 36m 30d

QoL follow-up Angio, IVUS follow-up MSCT follow-up (Absorb arm only)*

48m 60m

The ABSORB II study is sponsored by Abbott Vascular

Intent To Treat N=501

Absorb BVS N=335 N=334 N=331 N=324

(96.7%)

XIENCE N=166 N=166 N=165 N=163

(98.2%)

1 subject consent withdrawn 3 subjects consent withdrawn 2 subjects consent withdrawn 1 subject died

Baseline 30-day 180-day 1-year

1 subject consent withdrawn

N=329 N=164 2-year

2-Year Patient Flowchart

3 subjects consent withdrawn. 2 subjects died 1 subject consent withdrawn

1-year Summary

Absorb BVS N=335 XIENCE N=166 p value

Hierarchical PoCE*, % 7.3 9.1 0.47

All death (Non-hierarchical)

0.0 0.6 0.33

All MI (Non-hierarchical)

4.5 1.2 0.06

All revascularization (Non-hierarchical)

3.6 7.3 0.07

PoCE (Patient oriented Composite Endpoint)*: All death, all myocardial infarction, and all revascularisation.

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

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.

1-year Summary

Absorb BVS N=335 XIENCE N=166 p value

Hierarchical PoCE*, % 7.3 9.1 0.47

All death (Non-hierarchical)

0.0 0.6 0.33

All MI (Non-hierarchical)

4.5 1.2 0.06

All revascularization (Non-hierarchical)

3.6 7.3 0.07 Hierarchical DoCE* or TLF, % 4.8 3.0 0.35

Cardiac death (Non-hierarchical)

0.0 0.0 1.00

TV-MI (Non-hierarchical)

4.2 1.2 0.07

CI-TLR (Non-hierarchical)

1.2 1.8 0.69

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;115:2344-2351

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.

2-year Clinical Outcomes Composite Endpoints

Absorb BVS N=335 XIENCE N=166 p value

PoCE (%) 11.6

12.8 0.70

PoCE (Patient oriented Composite Endpoint): All death, all myocardial infarction, and all revascularisation

2-year Clinical Outcomes Composite Endpoints

Absorb BVS N=335 XIENCE N=166 p value

PoCE (%) 11.6

12.8 0.70

MACE (%)

7.6 4.3 0.16

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)

2-year Clinical Outcomes Composite Endpoints

Absorb BVS N=335 XIENCE N=166 p value

PoCE (%) 11.6

12.8 0.70

MACE (%)

7.6 4.3 0.16

DoCE, TLF (%)

7.0 3.0 0.07

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)

2-year Clinical Outcomes Composite Endpoints

Absorb BVS N=335 XIENCE N=166 p value

PoCE (%) 11.6

12.8 0.70

MACE (%)

7.6 4.3 0.16

DoCE, TLF (%)

7.0 3.0 0.07

TVF (%)

8.5 6.7 0.48

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)

Patient oriented Composite Endpoint (PoCE)

PoCE: All death, all myocardial infarction, and all revascularisation

PoCE (%)

5 10 15 20 25

Absorb BVS XIENCE

Time Post Index Procedure (Months)

90 180 270 360 450 540 630 720

2.4% 4.2% 7.3% 10.3% ∆=1.8% 37-day HR 1.75 [0.58,5.31] p=0.3151 37-758-day HR 0.69 [0.37,1.28] p=0.2317 ∆=-3.0%

MACE (%)

5 10 15 20 25

1.2% 4.2% 3.1% 3.5% ∆=3.0% ∆=0.4% 37-day HR 3.49 [0.79,15.34] p=0.0760 37-758-day HR 1.13 [0.39,3.24] p=0.8242

Time Post Index Procedure (Months)

90 180 270 360 450 540 630 720

Major Adverse Cardiac Events (MACE)

MACE: Cardiac death, all myocardial infarction, and clinically indicated target-lesion revascularisation

Absorb BVS XIENCE

DoCE/TLF (%)

5 10 15 20 25

Absorb BVS XIENCE

Time Post Index Procedure (Months)

90 180 270 360 450 540 630 720

1.2% 3.9% 1.8% 3.2% ∆=2.7% 37-day HR 3.24 [0.73,14.33] p=0.0996 37-758-day HR 1.71 [0.47,6.20] p=0.4109 ∆=1.4%

Device oriented Composite Endpoint (DOCE)/ Target Lesion Failure (TLF)

DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)

TVF (%)

5 10 15 20 25

Absorb BVS XIENCE

Time Post Index Procedure (Months)

90 180 270 360 450 540 630 720

1.8% 4.2% 4.5% 4.9% ∆=2.4% 37-day HR 2.33 [0.67,8.10] p=0.1683 37-758-day HR 0.89 [0.37,2.12] p=0.7914 ∆=-0.4% TVF : Cardiac death, all myocardial infarction, clinically indicated target-vessel revascularisation

Target Vessel Failure (TVF)

Clinical Outcomes Non Hierarchical Events

2 years

Absorb BVS N=335 XIENCE N=166 p value

Death* (%) 1.2 0.6 0.67

Cardiac

0.6 0.0 0.55

Non cardiovascular

0.6 0.6 1.00

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

Clinical Outcomes Non Hierarchical Events

2 years

Absorb BVS N=335 XIENCE N=166 p value

Death* (%) 1.2 0.6 0.67

Cardiac

0.6 0.0 0.55

Non cardiovascular

0.6 0.6 1.00 Myocardial Infarction (%) 5.8 2.4 0.10

Q-wave

1.5 0.6 0.67

Non Q-wave

4.3 1.8 0.16

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

Clinical Outcomes Non Hierarchical Events

2 years

Absorb BVS N=335 XIENCE N=166 p value

Death* (%) 1.2 0.6 0.67

Cardiac

0.6 0.0 0.55

Non cardiovascular

0.6 0.6 1.00 Myocardial Infarction (%) 5.8 2.4 0.10

Q-wave

1.5 0.6 0.67

Non Q-wave

4.3 1.8 0.16 Definite/Probable ST* (%) 1.5 0.0 0.17

Acute/sub-acute (0-30 days)

0.6 0.0 1.00

Late (31-365 days)

0.3 0.0 1.00

Very late (365 – 758 days)

0.6 0.0 0.55

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

Post-Procedure Usage of Antiplatelet Medication through 2 years

Absorb BVS N=335 XIENCE N=166 p value

On Aspirin (%)

at 1 year

95.8 95.2 0.75

at 2 years

92.2 92.2 0.99 On DAPT (%)

at 1 year

81.7 81.3 0.91

at 2 years

36.2 34.3 0.68

Very Late Scaffold Thrombosis Cases

Pre-dilatation Hiryu 2.75x10 mm

Absorb 3.0x18 mm, 10 atm Post-dilate Hiryu 3.25x10, 10 atm

MLD 3.44 mm %DS 20.5 MLD 1.84 mm %DS 39.0

Proximal D-max 3.00 mm, Distal D-Max 3.01 mm

acute gain 1.6 mm

Proximal MSA frame

SA 7.23 mm2 VD 3.03 mm LA 5.85 mm2 LD 2.73 mm LA 9.51 mm2 LD 3.48 mm Residual stenosis 21.5% Malapposition at proximal edge Suboptimal expansion

Possible cause : 1.Proximal stent malapposition 2.Suboptimal expansion definite very late ST 447 days

Malapposed struts

IVUS Post procedure

DAPT: Aspirin only at time of the event

Pre-dilatation Apex 3.0x12 mm Absorb 3.0x18 mm 10 atm = 3.20 mm

No post-dilatation

Proximal D-max 2.58 mm, Distal D-Max 2.84 mm

Proximal edge MLA frame

VA 20.77 mm2 VD 5.14 mm LA 6.26 mm2 LD 2.82 mm VA 18.36 mm2 VD 4.84 mm SA 5.13 mm2 SD 2.56 mm

Plaque burden 69.8% Incomplete coverage at distal edge Suboptimal expansion RAS 31.8%, Expansion index 0.59,

definite very late ST 602 days

Possible cause :

• 1. Suboptimal expansion
• 2. Incomplete coverage at edges

DAPT: Aspirin only at time of the event

Revascularizations* Non Hierarchical Events

2 years

Absorb BVS N=335 XIENCE N=166 p value

TLR (%) 2.7 1.8 0.76 NTL-TVR (%) 1.5 2.4 0.49 NTVR (%) 2.7 5.5 0.13 All revascularization 5.8 9.1 0.17

*Clinically indicated revascularizations per ARC. Cutlip et al.,

• Circulation. 2007;115:2344-2351

Limitations

• The ABSORB II study was not powered for clinical

endpoints

• The 2-year endpoint represents a non pre-specified

interim analysis

• Investigators long experience with XIENCE as

compared to Absorb BVS might have impacted the results

Conclusions

• At 2 years there were no significant differences in the

clinical outcomes between the two arms:

– PoCE (all death, all MI and all revascularization) Absorb BVS: 11.6% vs XIENCE: 12.8%, p=0.70 – DoCE/TLF (cardiac death, TV-MI and TLR) Absorb BVS: 7.0% vs XIENCE: 3.0%, p=0.07

• The exploratory observations presented in this report

are hypothesis generating and need to be confirmed in larger randomized trials such as ABSORB III