The ABSORB III randomized trial Gregg W. Stone on behalf of Stephen - - PowerPoint PPT Presentation

Outcomes of the ABSORB Bioresorbable Vascular Scaffold in Very Small and Not Very Small Coronary Arteries:

The ABSORB III randomized trial

Gregg W. Stone

• n behalf of Stephen G. Ellis, Charles Simonton,

Christopher Metzger, Ronald P. Caputo, David G. Rizik, Paul S. Teirstein, Jeffrey J. Popma, Jennifer Jones- McMeans, Zhen Zhang, Dean J. Kereiakes and the ABSORB III investigators

• ABSORB clinical trial program

study chairman (uncompensated)

• Consultant
• Abbott Vascular
• Reva Corp.

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.

ABSORB III: Study Flow

Patients with SIHD and stabilized ACS with 1-2 de novo lesions in different epicardial vessels with visually estimated RVD 2.50 - 3.75 mm and lesion length ≤24 mm were enrolled

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

Randomized 2:1 N=2008 (ITT) ABSORB N=1322 ABSORB N=1312 Xience N=677 99.2% Complete 98.7% Complete N=4 lost to follow-up N=6 withdrew consent N=6 lost to follow-up N=3 withdrew consent Xience N=686

12-month Follow-up

Stratified by diabetes, # of target lesions, and site

Sponsored by Abbott Vascular

Target Lesion Failure (1° EP)

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

• No. at Risk:

Absorb

TLF (%)

Xience

Months Post Index Procedure

20% 100% 80% 60% 40% 0% 1 2 3 4 5 6 7 8 9 10 11 12

1322 686 1254 661 1230 651 1218 643 1196 634

13

Diff [95% CI] = 1.7% [-0.5% to 3.9%] Pnoninferiority=0.007 Psuperiority=0.16 7.7% 6.0%

Absorb BVS (n=1322) Xience CoCr-EES (n=686)

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

Absorb (N=1322) Xience (N=686) p-value Device Thrombosis (def*/prob) 1.54% 0.74% 0.13

• Early (0 to 30 days)

1.06% 0.73% 0.46

• Late (> 30 to 1 year)

0.46% 0.00% 0.10

• Definite* (1 year)

1.38% 0.74% 0.21

• Probable (1 year )

0.15% 0.00% 0.55

*One “definite ST” in the Absorb arm by ITT was in a pt that was treated with Xience

Device Thrombosis to 1 Year

1-Year Device Thrombosis

Subgroup Absorb (N=1322) Xience (N=686) RR (95% CI) Relative Risk (95% CI) p-value (interaction) Age ≥64 years 1.8% 0.6% 3.22 (0.73-14.32) 0.38 Age <64 years 1.2% 0.9% 1.33 (0.36-4.99) Female 1.6% 2.0% 0.79 (0.23-2.78) 0.07 Male 1.5% 0.2% 7.21 (0.95-54.63) Diabetes 3.2% 1.4% 2.34 (0.67-8,13) 0.79 No diabetes 0.8% 0.4% 1.79 (0.37-8.56) Unstable angina/recent MI 1.0% 0.6% 1.88 (0.21-16.74) 0.91 Stable CAD 1.7% 0.8% 2.16 (0.73-6.42) Single TL/TV treated 1.6% 0.8% 2.09 (0.79-5.55) n/a Dual TL/TV treated 0.0% 0.0%

• Clopidogrel

1.8% 0.7% 2.69 (0.78-9.24) 0.33 Prasugrel or ticagrelor 0.8% 0.9% 0.96 (0.18-5.20) ACC/AHA class A or B1 0.8% 0.6% 1.36 (0.14-12.98) 0.67 ACC/AHA class B2 or C 1.9% 0.8% 2.32 (0.79-6.87) Lesion length <11.75 mm 1.4% 0.9% 1.58 (0.43-5.78) 0.56 Lesion length ≥11.75 mm 1.7% 0.6% 2.82 (0.63-12.67) RVD <2.63 mm 2.3% 0.9% 2.65 (0.77-9.07) 0.48 RVD ≥2.63 mm 0.8% 0.6% 1.28 (0.25-6.54) 0.1 1 10 100 Favors Absorb Favors Xience Ellis SG et al. N Engl J Med. 2015;373:1905-15

• Additional subgroup analyses were conducted to explore

the differences in device thrombosis rates between Absorb and Xience

• Given the thicker struts of Absorb, a biologically relevant

analysis was to examine outcomes in very small vessels

• We therefore performed detailed analyses according to

reference vessel diameter (RVD) by QCA

• Note: QCA under-estimates visually assessed vessel

diameter; 2.5 mm diameter by visual assessment (smallest RVD intended for Absorb) is ~2.25 mm by QCA

ABSORB III Analysis In Very Small Vessels

Lesions (n=2084)

QCA RVD <2.25 mm (median 2.09 [1.97, 2.19]) QCA RVD ≥2.25 mm (median 2.74 [2.49, 3.03])

408 (19.6%) 1676 (80.4%)

Patients (n=1998)

1 or 2 lesions with QCA RVD <2.25 mm All lesions with QCA RVD ≥2.25 mm

375 (18.8%) 1623 (81.2%)

Patients and Lesions with QCA RVD <2.25 mm

Comparison between Patients and Lesions with QCA RVD <2.25 mm vs. ≥ 2.25 mm

RVD <2.25 mm N=375 L=408 RVD ≥2.25 mm N=1623 L=1676 P-value Patient characteristics Age (years) Male Diabetes Current Tobacco Use Hypertension (requiring meds) Hyperlipidemia (requiring meds) Prior MI Stable CAD (vs. UA/recent MI) 64.6 ± 10.8 63.2% 35.6% 22.4% 83.7% 77.9% 25.4% 72.5% 63.3 ± 10.4 72.0% 30.9% 20.6% 80.3% 76.5% 20.9% 69.9% 0.03 0.0007 0.08 0.45 0.13 0.58 0.06 0.31 Lesion characteristics (QCA) Target vessel = LAD ACC/AHA class B2/C (vs. A/B1) Calcification (mod/sev) RVD (mm, mean ± SD) Diameter stenosis (%) Lesion length (mm, mean ± SD) 51.5% 58.5% 27.0% 2.09 ± 0.24 65.7% ± 11.6% 11.86 ± 5.95 41.9% 72.7% 34.2% 2.80 ± 0.38 65.4% ± 12.4% 12.99 ± 5.43 0.0005 <0.0001 0.006 <0.0001 0.61 0.0005

Device Diameter Implanted in Lesions with QCA RVD <2.25 mm vs. ≥ 2.25 mm (ITT*)

RVD <2.25 mm RVD ≥2.25 mm Per target lesion Absorb (NL=262) Xience (NL=146) Absorb (NL=1115) Xience (NL=561) Device diameter 2.25 mm 6 (2.3%) 4 (2.7%) 1 (0.1%) 5 (0.9%) 2.5 mm 177 (67.6%) 99 (67.8%) 185 (16.6%) 71 (12.7%) 2.75 mm 4 (1.5%) 19 (13.0%) 6 (0.5%) 49 (8.7%) 3.0 mm 78 (29.8%) 39 (26.7%) 486 (43.6%) 234 (41.7%) 3.25 mm 0 (0.0%) 1 (0.7%) 2 (0.2%) 21 (3.7%) 3.5 mm 15 (5.7%) 1 (0.7%) 498 (44.7%) 215 (38.3%) 4.0 mm 0 (0.0%) 0 (0.0%) 3 (0.3%) 19 (3.4%) Mean device dia (mm) 2.67 ± 0.27 3.13 ± 0.36

Note: Absorb was available in diameters 2.5, 3.0 and 3.5 mm with lengths 8, 12, 18 and 28 mm. Xience was available in diameters 2.25, 2.5, 2.75, 3.0, 3.5 and 4.0 mm with lengths 8, 12, 15, 18, 23, and 28 mm. *Includes crossovers; *P<0.0001

*

Device Thrombosis by Vessel Size

Any QCA RVD <2.25 mm vs. all RVD ≥2.25 mm

Any QCA RVD <2.25 mm 1-year results Absorb vs. Xience 4.6% vs. 1.5% respectively Diff [95%CI] = 3.1 [-0.3, 6.4]

Days Post Index Procedure

All QCA RVD ≥2.25 mm 1-year results Absorb vs. Xience 0.8% vs. 0.5% respectively Diff [95%CI] = 0.3 [-0.5, 1.1] Device Thrombosis (definite or probable) (%)

0% 2% 4% 6% 8% 10% 100 200 300 400 Days Post Index Procedure 0% 2% 4% 6% 8% 10% 100 200 300 400

Absorb XIENCE Absorb XIENCE

N=1623 N=375

Additive interaction P-value = 0.11

Device Thrombosis by Timing and Vessel Size

Device thrombosis (%)

3.3% 1.3% 0.6% 0.3% 1.5% 0.0% 0.6% 0.0%

0% 1% 2% 3% 4% 5% 0-30 day 30 day - 1 year 0-30 day 30 day - 1 year

Absorb Xience

QCA RVD ≥2.25 mm (N=1623) QCA RVD <2.25mm (N=375)

All P=NS

Example 1: Very small vessel enrolled in ABSORB III

QCA RVD 1.81 mm

Example 1: Very small vessel enrolled in ABSORB III

Post-BVS (final) RVD = 1.98 mm Dmax = 3.53 mm In-stent MLD = 2.05 mm In-segment MLD = 1.27 mm In-stent DS = -3.5% In-segment DS = 35.9%

Example 2: Very small vessel enrolled in ABSORB III

QCA RVD 1.98 mm

Example 2: Very small vessel enrolled in ABSORB III

Post-BVS (final) RVD = 2.12 mm Dmax = 2.44 mm In-stent MLD = 1.81 mm In-segment MLD = 1.81 mm In-stent DS = 14.6% In-segment DS = 14.6%

Subgroup Absorb N=242 Xience N=133 Relative Risk (95% CI) p-value (interaction) Age ≥65 years 5.1 0.0 n/a n/a Age <65 years 4.1 3.1 1.32 (0.26-6.63) Female 6.4 3.5 1.83 (0.37-9.08) n/a Male 3.8 0.0 n/a Diabetes 10.6 4.4 2.38 (0.54-10.56) n/a No diabetes 1.3 0.0 n/a Unstable angina/recent MI 3.1 3.2 0.95 (0.09-10.12) 0.28 Stable CAD 5.2 1.0 5.31 (0.68-41.28) Single lesion treated 4.1 1.0 3.98 (0.50-31.37) 0.77 Dual lesion treated 7.0 2.8 2.51 (0.27-23.11) Clopidogrel 5.2 2.2 2.30 (0.50-10.58) n/a Prasugrel or ticagrelor 2.5 0.0 n/a ACC/AHA class A or B1 3.2 1.8 1.77 (0.19-16.64) 0.57 ACC/AHA class B2 or C 5.5 1.3 4.30 (0.55-33.78) QCA lesion length <10.56 mm 5.3 1.5 3.45 (0.42-28.04) 0.88 QCA lesion length ≥10.56 mm 4.0 1.5 2.72 (0.32-22.81) QCA RVD <2.09 mm 3.8 0.0 n/a n/a QCA RVD ≥2.09 mm 5.7 3.3 1.73 (0.36-8.29) 0.1 1 10 Favors Absorb   Favors Xience

Device Thrombosis in RVD <2.25 mm Subgroup

Subgroup Absorb N=1074 Xience N=549 Relative Risk (95% CI) p-value (interaction) Age ≥64 years 1.1 0.7 1.58 (0.32-7.76) 0.97 Age <64 years 0.6 0.4 1.49 (0.16-14.21) Female 0.3 1.4 0.24 (0.02-2.62) 0.08 Male 1.1 0.3 4.19 (0.53-33.35) Diabetes 1.3 0.6 2.18 (0.25-19.32) 0.69 No diabetes 0.7 0.5 1.24 (0.24-6.37) Unstable angina/recent MI 0.6 0.0 n/a n/a Stable CAD 0.9 0.8 1.23 (0.32-4.73) Single lesion treated 0.9 0.6 1.37 (0.36-5.14) n/a Dual lesion treated 0.6 0.0 n/a Clopidogrel 1.1 0.3 3.70 (0.46-29.97) 0.16 Prasugrel or ticagrelor 0.5 1.1 0.47 (0.07-3.34) ACC/AHA class A or B1 0.0 0.0 n/a n/a ACC/AHA class B2 or C 1.2 0.7 1.65 (0.45-6.06) QCA lesion length <11.95 mm 1.2 0.4 3.05 (0.37-25.22) 0.33 QCA lesion length ≥11.95 mm 0.6 0.7 0.77 (0.13-4.59) QCA RVD <2.74 mm 1.0 0.7 1.33 (0.26-6.83) 0.78 QCA RVD ≥2.74 mm 0.7 0.4 1.95 (0.22-17.37) 0.1 1 10 Favors Absorb   Favors Xience

Device Thrombosis in RVD ≥2.25 mm Subgroup

TLF by Vessel Size

Any QCA RVD <2.25 mm vs. all RVD ≥2.25 mm

Absorb XIENCE

Any QCA RVD <2.25 mm 1-year results Absorb vs. Xience 12.9% vs. 8.3% respectively Diff [95%CI] = 4.6 [-1.7, 10.9]

TLF (%)

0% 5% 10% 15% 20% 25%

Days Post Index Procedure

50 100 150 200 250 300 350 400

TLF (%)

0% 5% 10% 15% 20% 25%

Days Post Index Procedure

50 100 150 200 250 300 350 400

Absorb XIENCE

All QCA RVD ≥2.25 mm 1-year results Absorb vs. Xience 6.6% vs. 5.5% respectively Diff [95%CI] = 1.2 [-1.3, 3.6]

N=1623 N=375

Additive interaction P-value = 0.31

1-Year Event Rates Absorb (N=242) XIENCE (N=133) Difference [95%CI] P-value TLF 12.9% 8.3% 4.6%

[-2.4%, 10.6%]

0.18

• Cardiac death

0.8% 0.0% 0.8%

[-2.0%, 3.0%]

0.54

• TV-MI

10.0% 4.5% 5.5%

[-0.5%, 10.5%]

0.06

• ID-TLR

6.6% 6.8%

• 0.1%1

[-6.3%, 4.9%]

0.96 Stent thrombosis 4.6% 1.5% 3.1%

[-1.2%, 6.8%]

0.15

Clinical Outcomes in Patients with Lesions with QCA RVD <2.25 mm (not intended for Absorb BVS)

• 1. Absorb = 6.64%; Xience = 6.77%

1-Year Event Rates Absorb (N=1074) XIENCE (N=549) Difference [95%CI] P-value TLF 6.7% 5.5% 1.1%1

[-1.5%, 3.4%]

0.38

• Cardiac death

0.6% 0.2% 0.4%

[-0.5%, 1.1%]

0.43

• TV-MI

5.2% 4.6% 0.5%2

[-1.9%, 2.6%]

0.64

• ID-TLR

2.2% 1.5% 0.8%3

[-0.8%, 2.1%]

0.29 Stent thrombosis 0.9% 0.6% 0.3%

[-0.8%, 1.1%]

0.76

Clinical Outcomes in Patients with all Lesions with QCA RVD ≥2.25 mm (indicated for Absorb BVS)

• 1. Absorb = 6.65%, Xience = 5.54%, difference = 1.12%
• 2. Absorb = 5.15%; Xience = 4.61%, difference = 0.54%
• 3. Absorb = 2.249%; Xience = 1.476%, difference = 0.773%

4.6% 8.1% 5.6% 2.0% 1.5% 2.5% 0.0% 0.0%

0% 2% 4% 6% 8% 10% 12%

Overall No post- dilatation Post-dilatation <14 atm Post-dilatation ≥14 atm

Absorb Xience

Absorb: 11/238 6/74 3/54 2/101 Xience: 2/133 2/79 0/15 0/36

1-Year ST in Very Small Vessels

Impact of Post-Dilatation and Pressure

Stent thrombosis (%)

RVD <2.25 mm

All P=NS

• The QCA RVD 2.25 mm cutoff was selected post

hoc, and randomization was not stratified by vessel size; we cannot exclude a role of baseline imbalances (including unmeasured confounders) in explaining some of the observed differences between devices

• The number of pts with lesions with QCA RVD <2.25

mm was modest (n=375), and while the patterns

• bserved are biologically and mechanistically

plausible, no significant differences were present between device types for any major clinical endpoint, nor were interaction p values significant

Limitations

• Compared to the thin strut XIENCE metallic

DES, the thicker strut Absorb BVS results in similar 1-year outcomes in coronary arteries with QCA RVD ≥2.25 mm, but may have higher event rates in very small vessels

• These findings have important implications for

device selection (and potentially technique) to

• ptimize 1-year outcomes when selecting

patients and lesions for Absorb BVS

ABSORB III Small Vessel Analysis Conclusions