the 2-year clinical outcomes of the absorb ii trial: first ... · the 2-year clinical outcomes of...

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 ChevalierInstitut Jacques Cartier, Massy, France

Patrick W. SerruysImperial College, London, UK

Erasmus University MC, Netherlands

on behalf of the ABSORB II Investigators

12 October 2015 - San Francisco, CA - U.S.APlenary 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)

TreatmentUp to 2 de novo lesions in different epicardial vesselsPlanned overlapping allowed in lesions ≤ 48 mm

Device SizesDevice diameters: 2.5, 3.0, 3.5 mmDevice 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

24m6m 12m 36m30d

QoL follow-upAngio, IVUS follow-upMSCT follow-up (Absorb arm only)*

48m 60m

The ABSORB II study is sponsored by Abbott Vascular

Intent To TreatN=501

Absorb BVSN=335

N=334

N=331

N=324

(96.7%)

XIENCEN=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withdrawn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withdrawn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withdrawn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withdrawn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withdrawn. 2 subjects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withdrawn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 BVSN=335

XIENCEN=166

p value

Hierarchical PoCE*, % 7.3 9.1 0.47All death (Non-hierarchical) 0.0 0.6 0.33

All MI (Non-hierarchical) 4.5 1.2 0.06All 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 MIDevelopment of new, pathological Q wave on the ECG.

• Non-Q wave MIElevation 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 BVSN=335

XIENCEN=166

p value

Hierarchical PoCE*, % 7.3 9.1 0.47All death (Non-hierarchical) 0.0 0.6 0.33

All MI (Non-hierarchical) 4.5 1.2 0.06All revascularization (Non-hierarchical) 3.6 7.3 0.07

Hierarchical DoCE* or TLF, % 4.8 3.0 0.35Cardiac death (Non-hierarchical) 0.0 0.0 1.00

TV-MI (Non-hierarchical) 4.2 1.2 0.07CI-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 Protocol Myocardial Infarction (MI):

• Q wave MIDevelopment of new, pathological Q wave on the ECG.

• Non-Q wave MIElevation 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 BVSN=335

XIENCEN=166

p value

PoCE (%) 11.6 12.8 0.70

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


Absorb BVSN=335

XIENCEN=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 revascularisationMACE (Major Adverse Cardiac Events):Cardiac death, all myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)


Absorb BVSN=335

XIENCEN=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 revascularisationMACE (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)


Absorb BVS N=335

XIENCEN=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 revascularisationMACE (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

Po

CE

(%)

0

5

10

15

20

25Absorb BVS XIENCE

Time Post Index Procedure (Months)

0 90 180 270 360 450 540 630 720

2.4%

4.2%7.3%

10.3%

∆=1.8%

37-day HR1.75 [0.58,5.31]

p=0.3151

37-758-day HR0.69 [0.37,1.28]

p=0.2317

∆=-3.0%

MA

CE

(%

)

0

5

10

15

20

25

1.2%

4.2%

3.1%

3.5%∆=3.0% ∆=0.4%

37-day HR3.49 [0.79,15.34]

p=0.0760

37-758-day HR1.13 [0.39,3.24]

p=0.8242


0 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

Do

CE

/TL

F (

%)

0

5

10

15

20

25Absorb BVS XIENCE


0 90 180 270 360 450 540 630 720

1.2%

3.9%

1.8%

3.2%∆=2.7%

37-day HR3.24 [0.73,14.33]

p=0.0996

37-758-day HR1.71 [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)

TV

F (

%)

0

5

10

15

20

25Absorb BVS XIENCE


0 90 180 270 360 450 540 630 720

1.8%

4.2%

4.5%

4.9%∆=2.4%

37-day HR2.33 [0.67,8.10]

p=0.1683

37-758-day HR0.89 [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 yearsAbsorb

BVS N=335

XIENCEN=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



2 yearsAbsorb

BVS N=335

XIENCEN=166

p value

Death* (%) 1.2 0.6 0.67

Cardiac 0.6 0.0 0.55


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



2 yearsAbsorb

BVSN=335

XIENCEN=166

p value

Death* (%) 1.2 0.6 0.67

Cardiac 0.6 0.0 0.55


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


Post-Procedure Usage of Antiplatelet Medication through 2 years

Absorb BVS

N=335

XIENCEN=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 malapposition2.Suboptimal expansion

definite very late ST 447 days

Malapposedstruts

IVUS Post procedure

DAPT: Aspirin only at time of the event

Pre-dilatation Apex 3.0x12 mm Absorb 3.0x18 mm10 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 mmLA 6.26 mm2 LD 2.82 mm

VA 18.36 mm2 VD 4.84 mmSA 5.13 mm2 SD 2.56 mm

Plaque burden 69.8%Incomplete coverage at distal edge

Suboptimal expansionRAS 31.8%, Expansion index 0.59,

definite very late ST 602 daysPossible cause : 1. Suboptimal expansion2. Incomplete coverage at edges

DAPT: Aspirin only at time of the event

Revascularizations* Non Hierarchical Events

2 yearsAbsorb

BVSN=335

XIENCEN=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

the 2-year clinical outcomes of the absorb ii trial: first ... · the 2-year clinical outcomes of...

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