Scaffolds: Results from the Randomized ABSORB III Trial Stephen G. - - PowerPoint PPT Presentation

Three-Year Clinical Outcomes with Everolimus-Eluting Bioresorbable Scaffolds: Results from the Randomized ABSORB III Trial Stephen G. Ellis MD

Dean J. Kereiakes MD and Gregg W. Stone MD for the ABSORB III Investigators

NCT01751906

• Consultant and research funding
• Abbott Vascular, Boston Scientific,

Medtronic

Affiliation/Financial Relationship Company

Disclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

The ABSORB III study is solely funded by Abbott Vascular

Background

• The Absorb everolimus-eluting PLLA-based BVS

provides early drug delivery and mechanical support functions similar to metallic DES, followed by complete bioresorption with recovery of vascular structure and function

• The ABSORB III trial demonstrated non-inferior rates
• f TLF (cardiac death, TVMI or ID-TLR) at 1 year in

2,008 patients with CAD randomized 2:1 to the Absorb BVS vs. Xience CoCr-EES

• Clinical outcomes through 3 years, the approximate

time of complete scaffold bioresorption, has not previously been reported from the ABSORB III trial

ABSORB III

2,250 pts with up to 2 de novo lesions in different epicardial vessels enrolled, with follow-up for 7-10 years, at up to 200 US and non-US sites

2,008 pts randomized 2:1 Absorb vs. Xience

(+50 lead-in pts and 200 pt non-randomized angio/IVUS/OCT/VM FU cohort)

RVD: 2.50 - 3.75 mm; Lesion length: ≤24 mm Scaffold diameters: 2.5, 3.0 and 3.5 mm Scaffold lengths: 12, 18, and 28 mm Follow-up: 30 days, 6 months, then yearly through 7-10 years (blinded after year 3) Primary endpoints: TLF at 1 year (non-inferiority) TLF between 3 and 7-10 years (pooled with ABSORB IV for superiority)

PIs: SG Ellis, DJ Kereiakes Study chairman: GW Stone

• >18 years old
• Evidence of myocardial ischemia (stable/unstable/post-

infarction angina or silent ischemia)

• No elevation of CK-MB
• 1 or 2 de novo target lesions in up to 2 native coronary

arteries (max 1 lesion per artery)

• Diameter stenosis ≥50% and <100% with TIMI flow ≥1

 If <70%, abnormal functional test (including FFR ≤0.80),

unstable angina or post-infarct angina

• RVD ≥2.50 mm and ≤3.75 mm (site-determined)
• Lesion length ≤24 mm (site-determined)

Key Patient Eligibility Criteria

Absorb (N=1322) (L=1385) Xience (N=686) (L=713) p-value Patient Characteristics Age (mean) 63.5 ±10.6 63.6±10.3 0.75 Male 70.7% 70.1% 0.80 Diabetes 31.5% 32.7% 0.60 Unstable angina 26.9 % 24.5% 0.25 Lesion Characteristics Lesion length, mm 12.6 ± 5.4 13.1 ± 5.8 0.048 RVD, mm 2.67 ± 0.45 2.65 ± 0.46 0.36 DAPT Usage DAPT at 1 year 89.9% 90.4% 0.71 DAPT at 3 years 55.8% 53.5% 0.32

Baseline Characteristics

Ellis SG et al. N Engl J Med 2015;373:1905-15

There were no major inter-group differences between baseline patient and lesion characteristics

Randomized 2:1 N=2008 (ITT) ABSORB N=1322 ABSORB N=1312 Xience N=677 Xience N=686

1-Year Follow-up

Study Flow and Follow-up

ABSORB N=1296 Xience N=671

2-Year Follow-up

N=4 lost to follow-up N=6 withdrew consent N=6 lost to follow-up N=3 withdrew consent N=10 lost to follow-up N=6 withdrew consent N=4 lost to follow-up N=2 withdrew consent

99.2% Complete 98.7% Complete 98.0% Complete 97.8% Complete

ABSORB N=1276 Xience N=661

3-Year Follow-up

N=14 lost to follow-up N=2 withdrew consent N=3 withdrawn by physician/site N=1 other N=8 lost to follow-up N=1 withdrew consent N=1 withdrawn by physician/site

96.5% Complete 96.4% Complete

Target Lesion Failure

The 3-year window includes follow-up through 37 months

Target lesion failure (%)

0% 5% 10% 15% 20% 25% 30% 6 12 18 24 30 36 42

HR [95% CI] = 1.31 [0.99, 1.73] p = 0.056 Time Post Procedure (Months)

• No. at Risk:

Absorb Xience 1322 686 1189 630 1074 577 1135 604

Absorb XIENCE

13.4% 10.4%

11.0% 8.1% 7.8% 6.2%

Target Lesion Failure: Landmark Analysis

0% 5% 10% 15% 20% 25% 30% 6 12 18 24 30 36 42

5.7% 7.5% 6.0% 7.0%

• No. at Risk:

Absorb Xience 1322 686 1200 636 1145 603 1215 635

Time Post Procedure (Months)

HR [95% CI] = 1.33 [0.92, 1.92] p=0.13 p=0.39 HR [95% CI] = 1.18 [0.81, 1.72]

0 – 1 Year 1 – 3 Years Target lesion failure (%)

4.1% 3.2%

Absorb XIENCE

Device Thrombosis

Device thrombosis (%)

0% 1% 2% 3% 4% 5%

Time Post Procedure (Months)

6 12 18 24 30 36 42

HR [95% CI] = 3.12 [1.21, 8.05] p = 0.01

• No. at Risk:

Absorb Xience 1322 686 1264 665 1197 630 1242 647

2.3% 0.7%

1.8% 0.7% 1.5% 0.7%

Absorb XIENCE

The 3-year window includes follow-up through 37 months

Device Thrombosis: Landmark Analysis

0% 1% 2% 3% 4% 5% 6 12 18 24 30 36 42

0.7% 1.5% 0.0% 0.8%

0.3% 0.0%

• No. at Risk:

Absorb Xience 1322 686 1273 668 1211 634 1256 651

Time Post Procedure (Months) Device thrombosis (%)

Absorb XIENCE HR [95% CI] = 2.08 [0.78, 5.55] p=0.13 p=0.02

0 – 1 Year 1 – 3 Years

Absorb (N=1322) XIENCE (N=686) HR (95%CI) P value TLF

13.4% (174) 10.4% (70) 1.31 [0.99, 1.73] 0.056

• Cardiac death

1.4% (18) 1.2% (8) 1.17 [0.51, 2.69] 0.71

• TV-MI

8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] 0.03

• ID-TLR

7.2% (92) 5.9% (39) 1.23 [0.85, 1.79] 0.27

Stent thrombosis

2.3% (30) 0.7% (5) 3.12 [1.21, 8.05] 0.01

• Definite

2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] 0.02

• Probable

0.2% (2) 0.0% (0)

• 0.31

Note: The 3-year window includes follow-up through 37 months

3-Year Clinical Events

Absorb (N=1322) XIENCE (N=686) HR (95%CI) P value All Death

3.1% (40) 3.4% (23) 0.90 [0.54, 1.51] 0.70

• Cardiac Death

1.4% (18) 1.2% (8) 1.17 [0.51, 2.69] 0.71

All MI

10.2% (132) 7.6% (51) 1.36 [0.98, 1.88] 0.061

• TV-MI

8.6% (112) 5.9% (40) 1.47 [1.02, 2.11] 0.03

• Related to

device thrombosis

1.9% (25) 0.6% (4) 3.26 [1.13, 9.35] 0.02

• Unrelated to

device thrombosis

6.8% (88) 5.3% (36) 1.28 [0.87, 1.88] 0.21

3-Year Clinical Events

Note: The 3-year window includes follow-up through 37 months

Absorb (N=1322) XIENCE (N=686) HR (95%CI) P value All revascularization

16.4% (210) 12.7% (85) 1.31 [1.02, 1.68] 0.04

• ID-TVR

11.6% (148) 7.7% (51) 1.54 [1.12, 2.11] 0.01

• All TLR

7.3% (93) 5.9% (39) 1.25 [0.86, 1.81] 0.25

• ID-TLR

7.2% (92) 5.9% (39) 1.23 [0.85, 1.79] 0.27

• Related to

device thrombosis

2.2% (28) 0.7% (5) 2.92 [1.13, 7.55] 0.02

• Unrelated to

device thrombosis

5.2% (66) 5.2% (34) 1.01 [0.67, 1.53] 0.96

3-Year Clinical Events

Note: The 3-year window includes follow-up through 37 months

Target Lesion Failure: Stratified by Vessel Size

0% 5% 10% 15% 20% 25% 30% 6 12 18 24 30 36 42 0% 5% 10% 15% 20% 25% 30% 6 12 18 24 30 36 42

Time Post Procedure (Months) Time Post Procedure (Months)

• No. at Risk:

Absorb Xience 242 133 182 101 206 119 193 109 1074 549 888 474 979 509 938 493

11.8% 9.4% 20.9% 14.9%

Target lesion failure (%) HR [95% CI] = 1.26 [0.91, 1.75] p = 0.16

Absorb XIENCE

HR [95% CI] = 1.49 [0.88, 2.52] p = 0.14

Absorb XIENCE

RVD <2.25 mm RVD ≥2.25 mm

18.4% 11.6% 12.9% 8.3% 9.4% 7.3% 6.6% 5.7%

Device Thrombosis: Stratified by Vessel Size

0% 2% 4% 6% 8% 10% 6 12 18 24 30 36 42 10% 0% 2% 4% 6% 8% 6 12 18 24 30 36 42

Time Post Procedure (Months) Time Post Procedure (Months)

• No. at Risk:

Absorb Xience 242 133 216 114 224 128 222 120 1074 549 977 514 1036 535 1016 525

1.7% 0.5% 5.0% 1.5%

HR [95% CI] = 3.08 [0.91, 10.47] p = 0.06

Absorb XIENCE

HR [95% CI] = 3.34 [0.75, 14.91] p = 0.09

Absorb XIENCE

RVD <2.25 mm RVD ≥2.25 mm

Device thrombosis %)

4.6% 1.5% 4.6% 1.5% 1.2% 0.5% 0.8% 0.5%

Device Thrombosis:

Landmark Analysis Stratified by Vessel Size

0% 2% 4% 6% 8% 10% 6 12 18 24 30 36 42

1.5% 4.6% 0.0% 0.4% Time Post Procedure (Months)

• No. at Risk:

Absorb Xience 242 133 223 115 224 129 229 121

Absorb XIENCE

RVD <2.25 mm

Device thrombosis %)

HR [95% CI] = 3.07 [0.68,13.85] p=0.12

0 – 1 Year

p=0.47

1 – 3 Years

0% 2% 4% 6% 8% 10% 6 12 18 24 30 36 42

0.5% 0.8% 0.0% 0.9% Time Post Procedure (Months)

1074 549 984 517 1044 537 1023 528

RVD ≥2.25 mm

HR [95% CI] = 1.53 [0.42,5.67] p=0.52

0 – 1 Year

p=0.03

1 – 3 Years

Absorb XIENCE

Multivariable Predictors: Absorb

Outcome Variable 0 – 3 Years Relative Risk [95% CI] P TLF Pre-procedure RVD <2.25 mm* 1.72 [1.28, 2.32] 0.0005 Prior coronary intervention 1.37 [1.04, 1.81] 0.023 Scaffold thrombosis Pre-procedure RVD <2.25 mm* 2.80 [1.37, 5.71] 0.006 Diabetes mellitus 2.77 [1.36, 5.64] 0.006

*By QCA

Variables entered into the TLF multiple model: ACC/AHA lesion class, age (median 64 years), treatment arm, calcification (moderate/severe), prior cardiac interventions, any diabetes, hypercholesterolemia requiring medication, sex, hypertension requiring medication, presentation (unstable angina and recent MI vs. stable ischemic syndrome), bifurcation, target vessel: LAD, target lesion length (mm, median), prior cardiac intervention, pre-procedure MLD (mm, median), number of target lesions, P2Y12 receptor antagonist (loading), pre-procedural RVD (<2.25 mm vs. ≥2.25 mm), current tobacco use. Variables entered into the ST multiple model: ACC/AHA lesion class, treatment arm, Any diabetes, presentation (unstable angina and recent MI vs. stable ischemic syndrome), target lesion length (mm, median), pre-procedural RVD (<2.25 mm vs. ≥2.25 mm).

Outcome Variable 0 – 3 Years Relative Risk [95% CI] P TLF Prior coronary intervention 2.45 [1.56, 3.85] <0.0001 Diabetes mellitus 1.59 [1.03, 2.47] 0.03 LAD target vessel 1.74 [1.12, 2.72] 0.01

There were no independent predictors of stent thrombosis.

Multivariable Predictors: XIENCE

Variables entered into the TLF logistic model: ACC/AHA lesion class, age (median 64 years), treatment arm, calcification (moderate/severe), prior cardiac interventions, any diabetes, hypercholesterolemia requiring medication, sex, hypertension requiring medication, presentation (unstable angina and recent MI vs. stable ischemic syndrome), bifurcation, target vessel: LAD, target lesion length (mm, median), prior cardiac intervention, pre-procedure MLD (mm, median), number of target lesions, P2Y12 receptor antagonist (loading), pre-procedural RVD (<2.25 mm vs. ≥2.25 mm), current tobacco use.

• ABSORB III enrolled patients with stable ischemic

heart disease and stabilized ACS, and excluded complex lesions

• Absorb is a first generation device and was used

for the first time by most operators within this trial

• The optimal implantation technique was still

evolving during the initiation and enrollment of ABSORB III - Detailed analysis of the impact of PSP on Absorb outcomes will be presented in the Featured Clinical Research session Tuesday 10/31 at 12:45 pm in Mile High Ballroom 1A-1B

Limitations

• In the large-scale ABSORB III trial, device-related

clinical events (TLF) continued to accrue between 1 and 3 years following PCI with both Absorb BVS and Xience EES, although to a slightly greater extent with BVS

• Three-year rates of composite adverse events were

increased with BVS compared to EES, driven by greater rates of scaffold thrombosis and TVMI

• Longer-term clinical follow-up is necessary to determine

whether more normal coronary structure and function after complete scaffold bioresorption will result in a favorable late net safety and efficacy profile of BVS compared to permanent metallic DES

Summary and Conclusions

ABSORB III 3-Year Publication

JACC 2017:on-line