Vai trò của stent tự tiêu trong điều trị bệnh lý nhiều thân mạch vành

BRS in Multivessel CAD
Faisal Latif, MD FACC FSCAI, Ramesh Daggubati, MD FACC FSCAI
Associate Chief of Cardiology
Director of Interventional Cardiology
Winthrop University Hospital
Mineola, NY USA


BVS ready for clinical use?
60 months

Symptom Severity

Yes !

Absorb A
Absorb B
Courage Trial Absorb Extend
Absorb II
Stents Vs Meds Absorb III/IV

Disease Severity

??

Syntax Trial
BVS Expand

DES Vs Surgery

#Fact 1. Despite a larger profile (ABSORB: 1.4mm, vs.
Xience 1.1mm), device success was 99.2% in B1/B2
lesions (98.3%).
In registries (e.g. ABSORB Expand), the device success
was 98.2% in complex lesions


Procedural characteristics
Absorb

Metallic DES

(n=187)

(n=365)

p-value

40.9%

35.6%

0.19

59.1%

64.4%

0.19

0.0%

0.0%

-

38.0%

48.2%

0.04

LMS

0.6%

2.2%

0.28

LAD

48.6%

53.3%

0.32

SVG

0.0%

0.0%

-

Clinical
Presentation
Stable angina
Unstable angina/
NSTEMI
STEMI
Multi-vessel disease
Treated Vessels†


Procedural characteristics
Procedural variables
Number of stents
Average Stent diameter,
mm
Total stent length, mm
Type of scaffold/
stent
Absorb
Everolimus-eluting stent
Bare-metal stent
Sirolimus-eluting stent
Others

Absorb

Metallic DES

(n=187)

(n=365)

p-value

2.16±1.32

1.51±0.83

<0.001

3.00±0.44

3.11±0.35

0.004

42.8±30.0

31.5±19.2

<0.001

100.0%

0.0%

0.0%
0.0%

96.2%
1.6%

0.0%
0.0%

0.8%
1.6%


Propensity Matched Comparison of
complete 6 months FU
• The overall follow-up rate was 95.7%.

Mortality
Myocardial infarction
Target-lesion
revascularization
Composite of death, MI
and TLR
Definite stent/scaffold
thrombosis

Acute/subacute
Late

Absorb

Drug-eluting
metallic stents

(n=187)
2.2%
1.7%

(n=365)
1.9%
0.0%

p-value
0.76
0.04

2.2%

1.1%

0.26

4.3%

3.0%

0.44

2.2%

0.0%

0.01

0.0%/0.0%
2.2%

0.0%/0.0%
0.0%

0.01


#Fact 2. Acute gain was reduced on QCA (ABSORB:
1.15mm vs. Xience: 1.46mm) and Q-IVUS (ABSORB:
2.9mm2 vs. Xience: 3.6mm2).
#Comment:
• Guidance on angiography for sizing and expansion.
• Angiography underestimate the luminal dimension
• Intravascular imaging for sizing and expansion might
have implication for FDA labeling.
Operator’s behavior
• Limited expansion of device
• Fear of scaffold disruption
• Use of a smaller postdilatation
balloon at a lower pressure

Reduced acute gain

Preparation strategy
• Protocol did not allow use
of adjunctive device
Acute recoil
• Not an issue


ABSORB FIRST REGISTRY
Diseased Vessels and Lesion Locations

RCA
LMCA 28.7%

Per Patient Analysis
# of diseased vessels
(Mean ± SD)

0.4%
1.6 ± 0.8

1 Vessel

56.6%

2 Vessels or more

43.4%

LCX

19.6%

LAD
51.3%

43.4% of patients had two or more diseased vessels

8


One Year Clinical Outcomes
Clinical Events

In hospital

1 year

0.1% (2)

0.8% (14)

0.1% (2)

0.6% (10)

MI
QMI
Non-QMI

0.7% (12)

0.1% (2)
0.6% (10)

1.4% (24)
0.4% (7)
1.0% (17)

All Revascularization

1.2% (20)

6.2% (106)

0.4% (6)

1.5% (25)

MACE

0.9% (16)

2.7% (46)

TLF (DoCE)

0.8% (13)

2.4% (40)

DMR (PoCE)

1.8% (30)

7.3% (125)

All Death
Cardiac Death

ID-TLR

Note: Clinical outcome data from those 1702 patients who complete 1 year follow-up
DoCE: device-oriented composite endpoint; PoCE: patient-oriented composite endpoint; DMR: all death, all MI, all
revascularization

9


Multivariate Logistic Regression
Predictor Analysis for TLF
Variable

Odds Ratio

P-value

Diabetes
(yes vs no)

2.24 [1.18, 4.34]

0.012

Overlap
(yes vs no)

2.44 [1.15, 4.76]

0.015

10


#Fact 2. Acute gain was reduced on QCA (ABSORB:
1.15mm vs. Xience: 1.46mm) and Q-IVUS (ABSORB:
2.9mm2 vs. Xience: 3.6mm2).
Mattesini et al. JACC 2014

=
=

=


#Fact 3. The definite scaffold/stent thrombosis rate was
0.6% (1 acute and 1 subsacute) in the ABSORB arm vs.
0% in the Xience arm.
In the ABSORB Extend registry (Ishibashi et al. EIJ 2014)
Non-Hierarchical % (n)

Scaffold Thrombosis (ARC Def/Prob)

• 2 cases
related to
interruption
of/ or
resistance
to DAPT

6 Months*

12 Months*

(N=450)

(N=450)

0.7 (3)

0.9 (4)

BVS
BVS

• 1 related to
overlap
• 1 unknown
cause

BVS overlap

2 subacute (day 6 and 29), 2 late(day 75 and 239)


#Fact 3. The definite scaffold/stent thrombosis rate was
0.6% (1 acute and 1 subsacute) in the ABSORB arm vs.
0% in the Xience arm.
Underexpansion - Yes
Overlap - Yes
Possible scaffold disruption -?
Malapposition –?
Alternance of high and low
shear stress on protruding
thick struts -?
• Thrombogenicity of PLLA –
No?
• Resistance or discontinuation
of DAPT - Yes
•
•
•
•
•


Small malapposition
Cut-off value of resolved ISA on OCT
Resolved ISA
Gutiérrez et al
2012 (Circ int)

<270μm

Kawamori et al
2013 (EHJ img)

<260μm


Mechanism of neointimal formation: Low ESS behind the strut will
lead to neointimal formation which will smooth luminal surface

RCA, Patient ID
100353-006
RCA, patient 1023

150
89


Large Uncorrectable Malapposition
18M

Post Proc
Dilemma: The vessel size is >4.0mm, while the
device size is 3.0mm…The operator is aware of
ISA, but considering the expansion limit of 3.5mm,
the operator cannot correct malapposition by
postdilatation.

1Y

Preprocedural sizing is
important!


Acute Disruption
In one patient out of 101 patients (ABSORB B study)
Overexpansion of a 3.0 mm ABSORB…
F

A

Ormiston et al.
Circ interv 2012

•
•

Pre

After Postdilatation

Stenosis in the OM branch treated
with a 3.0X18 mm ABSORB BVS
After Postdilatation with a
compliant 3.5-mm balloon at 16
atm (expected diameter, >3.96
mm), OCT shows appearances
consistent with strut breakage.

Acute Disruption
In one patient out of 101 patients (ABSORB B study)
Overexpansion of a 3.0 mm ABSORB…
Ormiston et al.
Circ interv 2012

1M later

•

•

1M later the
patient
presented with
recurrent angina
at rest.
OCT showed the
malapposed
struts in the
middle of the
lumen.


Def/Prob ST Ghost-EU registry
1.189 patients treated
with the Absorb scaffold

1.4%

Capodanno et al. Ghost EU registry, EuroIntervention 2014, ahead of print


Table 1. The rate of ST in individual populations *
Study (Journal /
international congress)

Population

Follow
up

Total,
N

Acute ST
in total,
N (%)

Subacute
ST in total,
N (%)

Early ST
in total,
N (%)

ST in
total, N

(%)

SAP,
N

ST in
SAP, N
(%)

ACS,
N

ST in
ACS, N
(%)

STEMI,
N

ST in
STEMI,
N (%)

Kraak et al., AMC Single Centre
(EIJ)

All-comers

6M

135

0(0%)

3 (2.2%)

3 (2.2%)

4 (3.0%)

82

1 (1.2%)

53

3 (5.7%)

17

0 (0%)

ABSORB FIRST (euroPCR2014)

All-comers

1M

800

0(0%)

2 (0.3%)

2 (0.3%)

2 (0.3%)

295

N/A

505

N/A

N/A

N/A

Azzalini et al. (euroPCR2014)

All-comers

N/A

339

0 (0%)

4 (1.2%)

4 (1.2%)

4 (1.2%)

N/A

3 (N/A)

N/A

0 (N/A)

N/A

1 (N/A)

Abizaid et al, ABSORB EXTEND
(EIJ)

SAP

12M

512

0 (0%)

2 (0.4%)

2 (0.4%)

4 (0.8%)

512

4 (0.8%)

-

-

-

-

Serruys et al., ABSORB B (EIJ)

SAP

36M

101

0 (0%)

0 (0%)

0 (0%)

0 (0%)

101

0 (0%)

-

-

-

-

Onuma et al., ABSORB A (JACC
int.)

SAP

60M

30

0 (0%)

0 (0%)

0 (0%)

0 (0%)

30

0 (0%)

-

-

-

-

CORONARY CTO(euroPCR2014)

SAP

6M

35

0 (0%)

0 (0%)

0 (0%)

0 (0%)

35

0 (0%)

-

-

-

-

Serruys et al., ABSORB II
(Lancet in press)

SAP / UAP

12M

335

1 (0.3)

1 (0.3)

2 (0.6)

3 (0.9%)

267

3 (1.1%)

68

0 (0%)

-

-

ASSURE registry (euroPCR2014)

SAP / UAP

12M

183

0 (0%)

0 (0%)

0 (0%)

0 (0%)

144

0 (0%)

39

0 (0%)

-

-

BVS EXPAND (euroPCR2014)

SAP / UAP

6M

200

0 (0%)

0 (0%)

0 (0%)

4 (2.2%)

N/A

N/A

N/A

N/A

-

-

Gori et al (EIJ)

ACS

1M

150

1 (0.7%)

1 (0.7%)

2 (1.4%)

4 (2.7%)

-

-

150

4 (2.7%)

66

N/A

POLAR ACS (euroPCR2014)

ACS

12M

100

0 (0%)

0 (0%)

0 (0%)

0 (0%)

-

-

100

0 (0%)

16

0 (0%)

Kajiya et al. (EIJ)

STEMI

3M

11

0 (0%)

0 (0%)

0 (0%)

0 (0%)

-

-

-

-

11

0 (0%)

Diletti et al. , BVS STEMI (EHJ)

STEMI

1M

49

0 (0%)

0 (0%)

0 (0%)

0 (0%)

-

-

-

-

49

0 (0%)

Kocka et al., PRAGUE-19 (EHJ)

STEMI

4M

41

0 (0%)

1 (2.4%)

1 (2.4%)

1 (2.4%)

-

-

-

-

41

1 (2.4%)

Wiebe et al. (Clin Res Cardiol)

STEMI

6M

25

0 (0%)

0 (0%)

0 (0%)

0 (0%)

-

-

-

-

25

0(0%)

Ielasi et al., RAI registry (EIJ in
press)

STEMI

6M

74

0(0%)

1(1.4%)

1(1.4%)

1(1.4%)

-

-

-

-

74

1(1.4%)

Average F/U: 10.6
Months

3120

0.06%

0.48%

0.54%

0.89%

1171

0.68%

410

1.71%

299

0.67%

All-comer

1189

5 (0.4%)

11 (0.9%)

16 (1.3%)

23 (2.1%)

626

9 (1.4%)

563

14
(2.5%)

192

4 (2.1%)

4309

0.16%

0.60%

0.76%

1.22%

1797

0.94%

973

2.16%

491

1.22%

When excluding the Ghost EU,
In 3120 patients with a mean follow-up of 10.6 Months,
• Acute ST: 0.06%
• Subacute ST : 0.48%
• Total ST: 0.89%
• SAP 0.68%, ACS 1.71%, STEMI 0.67%

When including the Ghost EU,
In 4309 patients with a mean follow-up of 10.3 Months,
• Acute ST: 0.16%
• Subacute ST : 0.60%
• Total ST 1.22%
• SAP 0.94%, ACS 2.16%, STEMI 1.22%

Weighted average
excluding the GHOST-EU
registry
Capodanno et al., GHOST (EIJ)

Weighted average
including the
GHOST-EU registry

6M

Average F/U: 10.3
Months

* ST= scaffold thrombosis, SAP= stable/silent angina pectoris, ACS=acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction


#Fact 4. Cardiac biomarker rise < 48 hours after the
index procedure and per-protocol peri-procedural MI did
not differ between the two arms.

Postprocedural CKMB rise
in the ABSORB Extend and
SPIRIT II/III

20.0%
18.0%

17.6%

35.0%
30.0%

16.0%

14.0%

Postprocedural CKMB rise
in the ABSORB II

12.5%

20.0%

10.0%

15.0%

8.0%

10.0%

4.0%
2.0%
0.0%

ABSORB
Xience

25.8%

25.0%

12.0%

6.0%

32.1%

5.5%

5.0%

3.8%
2.5% 1.9%
1.1%

0.0%
0.6%

>1xULN >2xULN >3xULN >5xULN

13.3%
9.8%
7.1%6.1%

4.9%
2.5%

0.6%
0.6%


#Fact 4. Cardiac biomarker rise < 48 hours after the
index procedure and per-protocol peri-procedural MI did
not differ between the two arms.
Incidence of anatomic complications assessed by angiography in patients with
periprocedural MI
Absorb BVS
(N=335 pts)

3.9%
2.7%
0%

EES
(N=166 pts)
1.2%
0.6%
0%

Side branch occlusion after device implantation

2.7%

0.6%

0.18

Side branch occlusion improvement after NTG

0%

0%

1

2.7%

0.6%

0.18

0.6%

0.6%

1

Abrupt closure
Distal embolization
coronary perforation
Flow limiting dissection (NHLBI type F)

0%
0.3%
0%
0%

0.6%
0%
0%
0%

0.33
1
1
1

coronary dissection after pre dilatation (NHLBI D or E)

0.3%

0%

1

coronary dissection after device implantation

0%

0%

1

Thrombus during procedure
Disruption of collateral flow

0%
0%

0%
0%

1
1

0.6%

0%

1

Per protocol peri-procedural MI
Type 1: Side Branch Occlusion, % (N)
Side branch occlusion after pre dilatation

Side branch occlusion after procedure
Type 2: Angiographic Other Complication, % (N)

Non-indentifiable mechanism causes, % (N)

p value
0.16
0.18
1


#Fact 4. Cardiac biomarker rise < 48 hours after the
index procedure and per-protocol peri-procedural MI did
not differ between the two arms.
When the cardiac biomarker rise was subcategorized
according to contemporary PMI criteria such as the 3rd
universal definition and the SCAI definition, PMI rates
were:
•
•
•
•

5·2% vs. 2·5% (CKMB >5x ULN)

32·0% vs. 26·9% (troponin >5x ULN, 3rd Universal)
0·6% vs. 0·6% (CKMB >10x ULN, SCAI)
4·6 % vs. 1·9 % (troponin >70x ULN, SCAI)

These results strongly emphasize the arbitrary
character of any definition of PMI.


ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China

Meta-analysis summary
BVS
(N=2164)

CoCr-EES
(N=1225)

RR [95% CI]
Fixed effect

P Value

I2

P
het

0.8%

0.7%

1.12 [0.47, 2.69]

0.80

NA

NA

- Cardiac

0.4%

0.3%

1.26 [0.33, 4.82]

0.74

NA

NA

- Non-cardiac

0.4%

0.4%

1.02 [0.32, 3.25]

0.97

NA

NA

5.7%

4.0%

1.34 [0.97, 1.85]

0.08

0%

0.71

2.9%

2.2%

1.29 [0.82, 2.03]

0.27

0%

0.75

- Peri-procedural (SCAI def)

0.8%

0.8%

0.97 [0.44, 2.14]

0.94

0%

0.63

- Non-peri-procedural (AIII def)

2.8%

1.8%

1.48 [0.91, 2.40]

0.11

0%

0.93

- TV-MI

5.1%

3.3%

1.45 [1.02, 2.07]

0.04

0%

0.80

- Non-TV-MI

0.7%

0.9%

0.75 [0.34, 1.66]

0.48

0%

0.94

All-cause mortality

All MI
- Peri-procedural (AIII def)

NA = not applicable - cannot test for heterogeneity because no events were present in one cell in 3
of the 4 trials; het = heterogeneity