ABSORB China : Two-Year Clinical - PowerPoint Presentation

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ABSORB China: Two-Year Clinical Results in Patients with Coronary Artery Disease Randomized to the Absorb Bioresorbable Vascular Scaffold Versus Metallic Drug-Eluting Stents

Runlin

Gao, M.D.

On behalf of ABSORB China Investigators

Disclosures

Runlin Gao

has

received a research grant

from

Abbott

Vascular.

Background

Previous 1-year results from ABSORB

China

showed that the primary endpoint of the study was successfully met and Absorb BVS was comparable

to XIENCE V in safety and effectiveness at

1 year.

It remains to be determined whether the

good clinical outcomes of the

Absorb

BVS

will sustain longer term.

ABSORB China* Treated with only the

study device

(Absorb BVS or XIENCE V) and with no mixed devices at target lesion and no pre-specified major protocol

deviations

Inclusion:

Up to 2

de novo

lesions in separate native coronary arteries

Lesion length ≤24 mm, RVD ≥2.5

mm

- ≤3.75 mm, %DS

≥50

% -

<100

%

Exclusion: AMI, EF <30%, eGFR <30 mL/min/1.73m2, LMCA, ostial lesion, excessive vessel tortuosity, heavy calcification, myocardial bridge, bifurcation with side branch ≥2 mm

Primary Endpoint: In-Segment Late Loss at 1 Yearin the Per-Treatment-Evaluable (PTE) Population*

1: 1 Randomization

Prospective, randomized, active control,

open-label, multicenter study in 480 subjects enrolled from 24 sites in China

Absorb BVS

Treat

with single study device

Diameters: 2.5, 3.0. 3.5 mmLengths: 8, 12, 18, 28 mm

XIENCE

V

Treat

with single study device

Diameters:

2.5, 3.0. 3.5 mm

Lengths:

8, 12, 18, 28 mm

Study Organization

Principal Investigator:

Runlin Gao, MD

Co-

Principal

Investigators:

Yuejin

Yang, MD, PhD, Yaling Han, MD, PhD, Yong Huo, MD

Study Chairman:

Gregg. W. Stone, MD

Angiographic

Core

Laboratory

:

Beth Israel Deaconess Medical Center, Inc. Data Safety Monitoring Board: CCRF (Beijing) Consulting Co. Ltd.

Clinical Events Committee: CCRF (Beijing) Consulting Co. Ltd.Sponsor:Abbott Vascular

Primary Endpoint:

In-Segment Late Loss at 1 Year (PTE)

Difference (Absorb BVS – XIENCE V)

NI Margin = 0.15 mm

1-Year

In-segment

LL

Absorb

BVS vs. XIENCE

V

0.19 ± 0.38 mm

(n=200)

vs. 0.13 ± 0.38 mm

(n=196

)

Difference = 0.06 mm [ -0.02, 0.14 ] PNI = 0.01PTE=459 subjects; 86.3% had the angiogram for the Primary Endpoint Analysis

Patient Flow and Follow-up (ITT)

Absorb BVS

(N=238)

Randomized

(

N=480)

Absorb BVS

(

N=241)

XIENCE V

(

N=239)

1-Year

Clinical

F/U

98.5%

Withdrawal (n= 3)

Withdrawal (n=2) & Death (n=5)

XIENCE V

(

N=232)

2

-Year

Clinical F/U

96.3%

XIENCE V

(

N=231)

Absorb BVS

(N=236)

Withdrawal (n= 1) & Death (n=1)

Death (n=1)

2-Year Clinical Composite EndpointsPoCE

=patient-oriented

composite endpoint

(all-cause

death, all MI*, or any revascularization); DoCE=device-oriented composite endpoint (cardiac death, TV-MI*, or ID-TLR); *

CK-MB

> 5x ULN for peri-procedural PCI

MI

Absorb BVS

(N=241)

XIENCE V

(N=239)

P-Value

PoCE

(DMR)

10.1% (24/237)

11.4% (27/237)

0.66

DoCE

(TLF)

4.2% (10/237)

4.6% (11/237)

0.82

MACE

5.1% (12/237)

5.1% (12/237)

1.00

TVF

5.5% (13/237)

6.8% (16/237)

0.57

* CK-MB > 5x ULN for

peri

-procedural PCI MI

2-Year

Clinical Component Endpoints

Absorb BVS

(N=241)

XIENCE V

(N=239)

P-Value

All-cause

death

0.4% (1/237)

2.5% (6/237)

0.12

- Cardiac death

0.4% (1/237)

1.3% (3/237)

0.62

All

MI*

3.0% (7/237)

2.1% (5/237)

0.56

- TV-MI*

2.1% (5/237)

0.8% (2/237)

0.45

All

revascularization

8.9% (21/237)

8.4% (20/237)

0.87

- ID-TLR

3.4% (8/237)

2.5% (6/237)

0.59

Target Lesion Failure (TLF)

TLF (%)

0

1

2

3

4

5

6

7

8

9

10

Time After Index Procedure (Days)

0

60

120

180

240

300

360

420

480

540

600

660

720

780

4.2%

4.7%

Absorb BVS

XIENCE V

Time (days)

0

37

208

298

393

758

Absorb

BVS (#

At

Risk)

238

235

234

234

230

227

XIENCE

V

(#

At Risk

)

237

234

230

229

225

223

3.4%

4.2%

1

-

y

ear

2-year

2

-year

HR [95% CI]= 0.90 [

0.38,2.11]

p=0.80 (Log rank

test

)

Cardiac Death

Cardiac Death (%)

0

1

2

3

4

5

Time After Index Procedure (Days)

0

60

120

180

240

300

360

420

480

540

600

660

720

780

0.4%

1.3%

Absorb BVS

XIENCE V

Time (days)

0

37

208

298

393

758

Absorb

BVS

(

#

At

Risk)

238

237

236

236

232

229

XIENCE

V

(#

At

Risk)

237

236

232

231

227

225

1.3%

0.0%

1

-

y

ear

2-year

2

-year

HR [95% CI]= 0.33 [0.03,3.16]

p=0.31 (Log rank test

)

TV-MI

Target Vessel MI (%)

0

1

2

3

4

5

6

7

8

9

10

Time After Index Procedure (Days)

0

60

120

180

240

300

360

420

480

540

600

660

720

780

2-year

HR [95% CI]= 2.48 [0.48,12.78]

p=0.26

(Log rank test)

2.1%

0.8%

Absorb BVS

XIENCE V

Time (days)

0

37

208

298

393

758

Absorb

BVS

(#

At

Risk)

238

235

235

235

234

231

XIENCE

V

(#

At

Risk)

237

234

231

230

230

229

0.8%

1.7%

1

-

y

ear

2-year

ID-TLR

ID-TLR (%)

0

1

2

3

4

5

Time After Index Procedure (Days)

0

60

120

180

240

300

360

420

480

540

600

660

720

780

2-year

HR [95% CI]= 1.31 [0.45,3.77]

p=0.62 (Log rank test)

3.4%

2.6%

Absorb BVS

XIENCE V

Time (days)

0

37

208

298

393

758

Absorb

BVS

(

#

At

Risk)

238

237

236

236

232

229

XIENCE

V

(#

At

Risk)

237

236

232

231

227

225

2.5%

2.1%

1

-

y

ear

2-year

Scaffold/Stent Thrombosis

Absorb BVS

(N=241)

XIENCE V

(N=239)

P-Value

All (0 -

730

days)

0.8% (2/237)

0.0% (0/231)

0.50

    Definite

0.4% (1/237)

0.0% (0/231)

1.00

    Probable

0.4% (1/237)

0.0% (0/231)

1.00

Early (0

– 30 days

)

0.4% (1/238)

0.0% (0/236)

1.00

Late

(31- 365 days)

0.0% (0/238)

0.0% (0/232)

1.00

Very Late

(

366- 730

days)

0.4% (1/237)

0.0% (0/231)

1.00

There were 1 probable,

subacute (1-30d)

ST and 1 definite, very late ST in the Absorb BVS

arm.

Absorb BVS

(N=241)

XIENCE V

(N=239)

P-Value

All (0 -

730

days)

0.8% (2/237)

0.0% (0/231)

0.50

    Definite

0.4% (1/237)

0.0% (0/231)

1.00

    Probable

0.4% (1/237)

0.0% (0/231)

1.00

Early (0

– 30 days

)

0.4% (1/238)

0.0% (0/236)

1.00

Late

(31- 365 days)

0.0% (0/238)

0.0% (0/232)

1.00

Very Late

(

366- 730

days)

0.4% (1/237)

0.0% (0/231)

1.00

Predictor Analysis of 2-Year TLF

14

0.90

[0.79, 1.03]

Max. Balloon Pressure Over the Entire Procedure (

atm

)

0.56

[0.23, 1.35]

Post Dilatation

(yes vs no

)

0.70

[0.24, 2.10]

Post-Procedure In-Segment MLD (mm)

2.21

[0.83, 5.88]

Post-Procedure RVD (mm)

7.49

[0.75, 75.2]

Post-Procedure Dissection

(yes vs no

)

2.14

[0.62, 7.39]

ACC/AHA Lesion Class

1.33

[0.55, 3.21]

Bifurcation

(yes vs no

)

1.07

[0.98, 1.17]

Target Lesion Length (mm)

0.85

[0.28, 2.59]

Pre-Procedure MLD (mm)

2.07

[0.80, 5.36]

Pre-Procedure RVD (mm)

2.52

[0.98, 6.46]

Moderate/Severe Calcification (yes vs no

)

0.82

[0.34, 1.97]

Target Vessel

(LAD vs no-LAD)

1.37

[0.57, 3.30]

Number of Diseased Vessel

(≥2 vs 1

)

0.79

[0.10, 6.12]

Number of Treated Target Lesions

(≥2 vs 1

)

2.05

[0.77, 5.47]

Prior MI

(yes vs no

)

0.55

[0.20, 1.56]

Angina

(yes vs no

)

1.06

[0.24, 4.71]

Prior Cardiac Interventions

(yes vs no

)

0.97

[0.39, 2.39]

Hypercholesterolemia Requiring Rx

(yes vs no

)

0.63

[0.26, 1.52]

Hypertension Requiring Rx

(yes vs no

)

1.82

[0.51, 6.47]

Diabetes Requiring Insulin

(yes vs no

)

1.18

[0.42, 3.31]

Diabetes Requiring Rx

(yes vs no

)

0.97

[0.35, 2.70]

Any Diabetes

(yes vs no

)

2.73

[1.13, 6.62]

Current Tobacco Use (yes vs no)

0.80

[0.29, 2.24]

Gender

(female vs male

)

1.02

[0.98, 1.06]

Age (years)

0.90

[0.38, 2.16]

Treatment

(Absorb BVS vs XIENCE V

)

Variables

OR

[95%CI]

Odds Ratio (OR)

0.001

0.01

0.1

1

10

100

1000

Predictors of 2-Year TLF

Variable

P

Value

Odds Ratio

[95% CI]

Odds Ratio

[95% CI]

Moderate/Severe

Calcification

(yes vs. no)

0.032

2.86

[1.10, 7.49]

Current Tobacco Use

(yes vs. no

)

0.039

2.61

[1.05, 6.47]

Calcification (moderate/severe) and smoking are two predictors of 2-year TLF

Limitations

Open-label study (potential for bias)

The primary endpoint was an objective measure of in-segment late loss analyzed by an independent angiographic core lab

Clinical events were adjudicated by an independent CEC

Non-complex patients and lesions enrolled Study population is typical of pivotal studies for approval

Sample size not powered for clinical endpoints

Summary and Conclusion (1)

Trial well conducted:

High clinical f/u rate: 1-year = 98.5%; 2-year = 96.3%

Independent CEC, angiographic core lab, and DSMB

100% data monitoring conducted by the sponsorAdditionally, an independent, third-party data verification by the sites’ GCP offices was performed as mandated by the new GCP regulations in China.

ABSORB

China met its primary endpoint of non-inferiority between Absorb BVS and XIENCE V for in-segment late loss at 1 year

.

Summary and Conclusion (2)

The rates of clinical events, including TLF,

cardiac death, TV-MI,

ID-TLR, and device thrombosis were generally low and comparable between Absorb

BVS and XIENCE V at 1 year. This trend of low event rates and comparable results between treatment arms continued at 2 years.Calcification (moderate/severe) and smoking are two predictors of 2-year TLF.

Thank you