the evolution of pci - stents - solaci

SOLACI – CACI 2014

The Evolution of PCI - Stents: From Bare Metal to DES, BVS & PLLA

George D. Dangas, MD, FACC, FSCAI, FESC

Mount Sinai Medical Center

New York, NY


Sirolimus-eluting stent: 7 year F/U

Pre Post 1 Year

2 Years 4 Years 7 Years


Drug-eluting Stents: 1st Generation TA

XU

S

Polyolefin derivative Paclitaxel

Drug Polymer Stent

Cyphe

r

PEVA + PBMA blend Sirolimus BX Velocity

Liberté


1st Gen Drug-Eluting Stents

The good, the bad, and the ugly!

7 years

40 mos

BMS DES

Incomplete

apposition

Late stent

thrombosis -20

-15

-10

-5

0

5

10

15

20

25

Prox. Ref. Prox. Stent Distal Distal Ref.

Abn Vasomotion

*P<0.001 vs. control

Sirolimus

Control

* *

Delayed Healing!

Angioscopy

BMS

DES Late loss = 0

Eos

Giant cells

IVUS

Inflammation


All-Cause Mortality: All SES/PES RCTs

I-V Overall (I-squared = 0.0%, p = 0.918)

BASKET (SES only)

TAXUS II

HAAMU-STENT

Seville

Ortolani et al

TAXUS IV

E-SIRIUS

Study ID

DIABETES

PRISON II

STRATEGY

RAVEL

SES-SMART

TAXUS V

Typhoon

MISSION!

SCORPIUS

SESAMI

D+L Overall

Passion

C-SIRIUS

Pache et al

SIRIUS

0.97 (0.81, 1.15)

0.82 (0.37, 1.84)

1.61 (0.57, 4.53)

2.00 (0.63, 6.38)

1.35 (0.23, 7.78)

2.00 (0.19, 21.38)

0.89 (0.63, 1.25)

1.08 (0.25, 2.24)

ES (95% CI)

1.44 (0.48, 4.33)

0.50 (0.09, 2.67)

0.84 (0.36, 1.96)

1.75 (0.73, 4.16)

0.21 (0.02, 1.71)

0.97 (0.57, 1.65)

1.01 (0.38, 2.65)

0.48 (0.09, 2.59)

1.28 (0.35, 4.61)

0.43 (0.11, 1.63)

0.97 (0.81, 1.15)

0.70 (0.36, 1.36)

0.68 (0.11, 4.04)

1.40 (0.45, 4.35)

1.02 (0.67, 1.54)

100.00

4.80

2.87

2.30

1.00

0.55

26.29

2.57

(I-V)

2.55

1.07

4.30

4.08

0.62

10.92

3.27

1.09

Weight

1.86

1.70

6.99

0.95

2.40

17.82

%

0.97 (0.81, 1.15)

0.82 (0.37, 1.84)

1.61 (0.57, 4.53)

2.00 (0.63, 6.38)

1.35 (0.23, 7.78)

2.00 (0.19, 21.38)

0.89 (0.63, 1.25)

1.08 (0.25, 2.24)

ES (95% CI)

1.44 (0.48, 4.33)

0.50 (0.09, 2.67)

0.84 (0.36, 1.96)

1.75 (0.73, 4.16)

0.21 (0.02, 1.71)

0.97 (0.57, 1.65)

1.01 (0.38, 2.65)

0.48 (0.09, 2.59)

1.28 (0.35, 4.61)

0.43 (0.11, 1.63)

0.97 (0.81, 1.15)

0.70 (0.36, 1.36)

0.68 (0.11, 4.04)

1.40 (0.45, 4.35)

1.02 (0.67, 1.54)

100.00

4.80

2.87

2.30

1.00

0.55

26.29

2.57

(I-V)

2.55

1.07

4.30

4.08

0.62

10.92

3.27

1.09

Weight

1.86

1.70

6.99

0.95

2.40

17.82

%

1.1 1 10

8,867 pts, 21 trials, mean F/U 2.9 years

Favors BMS

Estimate (95% CI) Weight (%)

0.97 (0.81,1.15)

0.97 (0.81,1.15), p=0.72

Random Effects

*Fixed Effects (I2=0.0%)

Favors DES

Kirtane A et al. Circulation. 2009;119:3198-3206


MI: All SES/PES RCTs 8,850 patients, 20 trials , mean F/U 2.9 years

D+L Overall (I-squared = 3.0%, p = 0.420)

I-V Overall

SCORPIUS

TAXUS II

PRISON II

TAXUS V

Passion

STRATEGY

MISSION!

Typhoon

SIRIUS

TAXUS IV

BASKET (All)

RAVEL

Ortolani et al

DIABETES

HAAMU-STENT

Study ID

E-SIRIUS

SES-SMART

SCANDSTENT

SESAMI

C-SIRIUS

1.1 1 10

I-V Overall (I-squared = 3.0%, p = 0.420)

SESAMI

Passion

C-SIRIUS

RAVEL

TAXUS IV

TAXUS V

SCORPIUS

SIRIUS

DIABETES

MISSION!

E-SIRIUS

SCANDSTENT

Study ID

Ortolani et al

SES-SMART

STRATEGY

HAAMU-STENT

BASKET (All)

Typhoon

TAXUS II

PRISON II

D+L Overall

0.94 (0.79, 1.13)

1.00 (0.20, 4.88)

0.83 (0.26, 2.69)

0.59 (0.14, 2.47)

1.24 (0.49, 3.14)

0.99 (0.66, 1.48)

1.27 (0.79, 2.04)

0.82 (0.23, 2.95)

0.96 (0.59, 1.55)

0.60 (0.20, 1.50)

0.62 (0.28, 1.39)

1.94 (0.93, 4.02)

0.33 (0.09, 1.18)

ES (95% CI)

1.50 (0.26, 8.61)

0.16 (0.04, 0.67)

0.82 (0.31, 2.40)

0.25 (0.03, 2.19)

1.15 (0.64, 2.08)

0.80 (0.22, 2.97)

0.63 (0.23, 1.72)

0.83 (0.26, 2.64)

0.94 (0.78, 1.13)

100.00

1.29

2.40

1.59

3.80

20.13

Weight

14.59

2.02

14.07

3.23

5.11

6.13

%

1.98

(I-V)

1.07

1.65

3.13

0.71

9.45

1.94

3.24

2.44

1.1 1 10


0.94 (0.78,1.13)

0.95 (0.79,1.13), p=0.54

Favors DES Favors BMS

Random Effects

*Fixed Effects (I2=3.0%)

Kirtane A et al. Circulation. 2009;119:3198-3206


TVR: All SES/PES RCTs

NOTE: Weights are from random effects analysis

D+L Overall (I-squared = 53.2%, p = 0.006)

Pache et al

Study ID

HAAMU-STENT

C-SIRIUS

Typhoon

STRATEGY

SIRIUS

SCANDSTENT

TAXUS II

PRISON II

TAXUS IV

E-SIRIUS

MISSION!

Ortolani et al

SESAMI

I-V Overall

TAXUS V

RAVEL

0.45 (0.37, 0.54)

0.38 (0.23, 0.64)

ES (95% CI)

0.33 (0.09, 1.19)

0.30 (0.10, 0.93)

0.42 (0.25, 0.69)

0.34 (0.16, 0.77)

0.48 (0.37, 0.62)

0.17 (0.09, 0.33)

0.61 (0.35, 1.08)

0.37 (0.19, 0.69)

0.57 (0.45, 0.72)

0.35 (0.21, 0.56)

0.38 (0.17, 0.85)

0.58 (0.25, 1.36)

0.36 (0.17, 0.79)

0.51 (0.45, 0.57)

0.77 (0.60, 0.98)

0.51 (0.25, 1.04)

100.00

7.14

(D+L)

1.91

2.45

7.20

4.22

11.51

5.44

%

6.44

5.49

11.94

Weight

7.45

4.08

3.78

4.36

11.75

4.83

1.1 1 10

7,291 patients, 16 trials , mean F/U 3.2 years

Favors DES Favors BMS


0.45 (0.37,0.54), p<0.001

0.51 (0.45,0.57)

*Random Effects (I2=53.2%)

Fixed Effects


Target Lesion Revascularization at 5 Years TAXUS I, II-SR, IV & V

12.3% (n=162)

21.0% (n=284)

5-Year HR [95% CI]:

0.53 [0.44, 0.65]

P<0.001

0%

0 1 2 3 4 5

30%

20%

10%

TLR (

%)

BMS (n=1397)

TAXUS (n=1400)

Years

Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42


Myocardial Infarction: Landmark Analysis TAXUS I, II-SR, IV & V (n=2,797)

0%

5%

10%

0 1 2 3 4 5

4.0%

4.5%

2.3%

3.8%

Years

Event Rate ± 1.5 SE

1-5 Year HR [95% CI]:

1.67 [1.06, 2.65]

P=0.03 0-1 Year HR [95% CI]:

0.89 [0.62, 1.27]

P=0.52

Myo

ca

rdia

l in

farc

tio

n (

%)

BMS (n=1397)

TAXUS (n=1400)

Stone GW et al. JACC CV Int 2011;4:530–42

Mohr FW et al. Lancet 2013

5-year GO and ST in SYNTAX • P.W. Serruys TCT • Miami, FL • 22 October 2012 • Slide 11 SOLACI – CACI 2014

SYNTAX: Definite/Probable ARC Stent Thrombosis to 5 Years (Per Patient)

0

6

12

(3/896) (23/893) (15/874) (11/850) (12/830)

Days Post-procedure

Acute ≤1d

Subacute 2-30d

Late 31-365d

Very Late

(10/803) (7/768)

366- 730d

731- 1095d

1096- 1460d

1461- 1825d

0

6

12

10.4

(76/730)

Total 5 year

0.3

2.6

1.7 1.3 1.4 1.2

0.9

Rate was ~ same in the LM and 3VD cohorts, and roughly independent of Syntax Score

Farooq V et al. JACC 2013:62:2360–9

~4.5% ST

in year 1

~1.2% ST/yr

in years 2-4

5-year GO and ST in SYNTAX • P.W. Serruys TCT • Miami, FL • 22 October 2012 • Slide 12 SOLACI – CACI 2014

MACCE following Stent Thrombosis (Per Protocol Defn, Per Patient [n=47 STs])

Cardiac Death 30% (n=14)

Nonfatal MI 36% (n=17)

Revascularization only 34% (n=16)

47/903 MACCE (5.2%) attributed to stent thrombosis

~1/3 of pts with ST died

~2/3 of pts with ST had death or MI

100% of pts with ST had MACCE

Farooq V et al.

JACC 2013:62:2360–9


Drug-eluting Stents: 2nd Generation

Drug Polymer

Xie

nce V

VDF + HFP copolymer Everolimus Vision

O

O

O O HO

O

O

O O H O

O O

N O

H O

Stent

Pro

mu

s

Ele

men

t

VDF + HFP copolymer Everolimus Element (Ion)

O

O

O O HO

O

O

O O H O

O O

N O

H O


Stent Thrombosis is Affected by Stent

Design, Deployment and Polymer

Kolandaivelu K et al. Circulation 2011;123:1400-09

Impact of Xience / Promus polymer coating

In vitro pulsatile Chandler loop model with porcine blood

LD

H A

dso

rban

ce

Rela

tiv

e p

late

let

ad

hesio

n

24%

P=0.002

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0

ML VISION (81 µm) XIENCE V (96.6 µm)


SPIRIT II, III, IV and COMPARE trials

Pooled database analysis (n=6,789)

Stent thrombosis (ARC def/prob) at 2 years

Planer D et al. JACC Cardiovasc Interv. 2011;4:1104-15

1,8

2,9

0,7 0,7

0

1

2

3

4

Stable angina ACS

2-y

r S

ten

t th

rom

bo

sis

(%

)

Taxus (PES) Xience V (EES)

0.25 (0.12–0.52)

P=0.0002 0.34 (0.19–0.62)

P=0.0002


Stent Thrombosis

Baber U, …, Dangas G JACC 2011


Target Vessel Revascularization



Myocardial Infarction



Statistical Model

Random (13)

Fixed (13)

Clopidogrel Duration

6 months (5)

12 months (7)

Follow-up

≤ 1 year (12)

> 1 year (7)

DES

PES (5)

ZES (1)

SES (7)

Stent Thrombosis TVR MI

0,1 1 10 0,4 4 0,4 4

Favors EES Favors non-EES Favors EES Favors non-EES Favors EES Favors non-EES


ST Regression Analysis

-3,5

-2,5

-1,5

-0,5

0,5

0 1 2 3 4

Non everolimus-eluting drug eluting stent ST rate, %

Ris

k D

iffe

ren

ce,

%

R2=0.89, p<0.001 Sirolimus eluting stent

Zotarolimus eluting stent

Paclitaxel eluting stent



EXAMINATION Trial

0 1 2 3

Xience V

Vision

Acute Subacute Late

p = 0.01

1504 pts with STEMI undergoing PCI within 48 (85% primary PCI

within 12) were randomized to Xience V EES vs. Vision BMS

Stent thrombosis (Def/prob) within 1 year

2.6%

0.9%

Definite ST was reduced with Xience V from 1.9% to 0.5%, p=0.01

Sabate M et al. Lancet 2012


Stent Thrombosis Network Meta-analysis Primary EP: ARC Definite ST (FU through 2 years)

49 RCTs, 50,844 pts

Evidence

network

Palmerini T et al. Lancet 2012:On-line

9 studies PES BMS

SES End-ZES

Res-ZES Pt-Cr-EES

CoCr-EES

6 studies


Stent Thrombosis Network Meta-analysis ARC Definite ST at 1 year

49 RCTs, 50,844 pts

Odds Ratio

[95%] 1-year definite stent thrombosis*

CoCr-EES vs BMS

CoCr-EES vs PES

CoCr-EES vs SES

CoCr-EES vs Res-ZES

CoCr-EES vs End-ZES

SES vs BMS

End-ZES vs SES

0.23 (0.13-0.41)

0.28 (0.16-0.48)

0.41 (0.24-0.70)

0.14 (0.03-0.47)

0.21 (0.10-0.44)

0.57 (0.36-0.88)

1.92 (1.07-3.90)

Favors Stent 1 Favors Stent 2

10 1 0.1 0.01

*Only statistically significant

results are shown Palmerini T et al. Lancet 2012:On-line


0

1

2

3

4

5

6

0 3 6 9 12 15 18 21 24 27 30 33 36

PLATINUM: Target Lesion Failure

Months Since Index Procedure

CoCr-EES

PtCr-EES

No. at risk

4-Year Follow-up (Primary Endpoint at 1 Year)

749 738 735 715 701 683 656 473

758 747 745 727 715 702 687 480

CoCr-EES (N=749)

PtCr-EES (N=758)

0

3

6

9

12

15

0 6 12 18 24 30 36 42 48

TL

F (

%) 8.5%

7.4%

Treatment Group PROMUS Element 0-4YPROMUS 0-4Y

Primary Endpoint

HR [95% CI] =

0.86 [0.60, 1.24]

P = 0.43

Kereiakes DJ et al. JACC 2014;63 (12):2905-4 (SuppA)


Reso

lute

BioLinx Zotarolimus Driver

Drug Polymer Stent

Zotarolimus-eluting DES: 2nd Generation

Hydrophilic

Hydrophobic

En

deavo

r

Phosphorylcholine Zotarolimus Driver


Days after Initial Procedure

Cu

mu

lati

ve In

cid

en

ce o

f E

ven

ts

11.2% 10.7%

0%

0 180 360 540 720

20%

5%

15%

10%

EES (n=1,152)

R-ZES (n=1,140)

95% CI = 0.6% [-2.0%, 3.2%]

P = 0.73

RESOLUTE All-Comers: TLF (Cardiac Death, TV-MI or clinically-driven TLR)

Silber S et al. Lancet. 2011;377:1241-7


TWENTE (n=1,387)

Target Vessel Failure at 2-Year Follow-up

Tandjung K et al. J Am Coll Cardiol 2013;61:2406–16

0 60 120 180 240 300 360 420 480 540 600 660 720

TV

F (

%)

Follow-up (days)

0

5

10

15

20

25

30

Xience V (n=692)

Resolute (n=695)

P = 0.67

11.6%

10.9%


Endeavor ZES

PROTECT Study Design

Largest RCT and first powered for ST

Cypher SES

6mo 4yr 3yr 30mo 18mo 24mo 12mo Clinical endpoints

5yr 30d

Real-world patients – N=8709 Single and multiple coronary artery lesions No limitations on number of lesions/vessels

1:1 Randomization

196 sites world wide in 5 continents

3-12 months of aspirin and clopidogrel

Primary endpoint: ARC definite or probable ST at 3 years

Powered for a 40% reduction with ZES

Camenzind E et al. Lancet 2012


Definite or probable stent thrombosis to 3 years

Patients at Risk

E-ZES 4357 4347 4222 4119

C-SES 4352 4344 4211 4100

PROTECT Primary Endpoint

Time After Initial Procedure (Years)

AR

C D

efi

nit

e / P

rob

ab

le S

T

0%

0 1 3

5%

2%

2

1%

Endeavor ZES (N = 4357)

Cypher SES (N = 4352)

1.42%

1.79%

3%

4%


HR [95%CI =

0.81 [0.58-1.14]

P=0.22


Definite or probable stent thrombosis to 3 years

PROTECT Primary Endpoint


0,7

0,4 0,3

0,6

0,1

1,1

0

0,3

0,6

0,9

1,2

1,5

Ste

nt

thro

mb

osis

(%

)

Cypher SES (n = 4159) Endeavor ZES (n = 4181)

Late

(1 -12 months)

Early

(0-30 days)

Very late

(1-3 years)

P = 0.60

P = 0.02

P<0.001


Sarno G et al. EHJ 2012;33:606–13

Relative Distribution of Stent Types

BMS vs 1st Gen DES vs. 2nd Gen DES SCAAR: 94,384 consecutive pts in Sweden 2006-2010

(BMS 64,631; 1st gen DES 19,202; 2nd gen DES 10,551 1st gen = Cypher, Taxus , Endeavor. 2nd gen = Resolute, Xience, Promus Element

2006-1

1

20%

Year and month

2007-0

1

40%

0%

60%

80%

100%

2007-0

3

2007-0

5

2007-0

7

2007-0

9

2007-1

1

2008-0

1

2008-0

3

2008-0

5

2008-0

7

2008-0

9

2008-1

1

2009-0

1

2009-0

3

2009-0

5

2009-0

7

2009-0

9

2009-1

1

2010-0

1

2010-0

3

2010-0

5

2010-0

7

2010-0

9

1st gen DES 2nd gen DES

BMS


BMS vs 1st Gen DES vs. 2nd Gen DES SCAAR: 94,384 consecutive pts in Sweden 2006-2010

(BMS 64,631; 1st gen DES 19,202; 2nd gen DES 10,551 1st gen = Cypher, Taxus , Endeavor. 2nd gen = Resolute, Xience, Promus Element

Sarno G et al. EHJ 2012;33:606–13

Adjusted Event Rates: Death

Months

Adj HR of 2nd gen DES

vs. 1st gen DES: 0.77 [0.63–0.95]

vs. BMS: 0.55 [0.46–0.67]

BMS

1st gen DES

2nd gen DES

6%

0

5%

4%

3%

2%

1%

0%

3 6 9 12 15 18 21 24

De

ath

(%

)


Number at risk

XIENCE V 2458 2390 2364 2323 2281 2238 2212 2187 2162 2132 2116 2095 2074

TAXUS 1229 1166 1138 1119 1095 1069 1060 1049 1029 1019 1008 994 979

Targ

et

lesio

n f

ailu

re (

%)

Months

XIENCE V (n=2,458)

TAXUS Express (n=1,229)

p=0.02

HR [95%CI] =

0.78 [0.63, 0.97]

6.7%

4.0%

p=0.001

HR [95%CI] =

0.61 [0.46, 0.81]

Δ 2.7%

0

5

10

15

20

25

0 3 6 9 12 15 18 21 24 27 30 33 36

11.7%

9.2%

Δ 2.5%

p=0.004

HR [95%CI] =

0.71 [0.56, 0.90]

SPIRIT IV: Target Lesion Failure @3 years

TLF = cardiac death, target vessel MI, or ischemic-driven TLR

Stone GW et al. JACC 2011 (abstract)

~2.6%/yr event rate after year 1


15-year Follow-up After BMS (1990-1993)

N=405

Yamaji K et al. Circ CV Int 2010

Sudden

death

Cardiac

death

All-cause

death

All-cause

death /MI/

revasc

All-cause

death/MI

83.8%

Years after Stent Implantation

51.6%

45.4%

20.6%

7.1%

100

80

60

40

20

0

0 5 4 10 15 20

Cardiac

death/

TV-MI

Cardiac

death/

TV-MI/

TLR

Years after Stent Implantation

50.6%

25.5%

100

80

60

40

20

0

0 5 4 10 15 20

~2.1%/yr event

rate after year 1


Very Late Adverse Events After BMS

Yamaji K et al. Circ CV Int 2010

Pre Post 5 years 15 years



In-stent restenosis at 15 years

Stent thrombosis at 17 years

Aneurysm formation at 13 years


Etiology of metallic stent events beyond 1 yr

Very late thrombosis and restenosis

Possible causes

1. Uncovered stent struts (thrombosis)

2. Persistent stimulation of SMCs, from adherent fibrin

and/or loss of normal vessel curvature

3. Abnormal shear stress from protruding struts and/or

loss of cyclic strain relief (compliance mismatch)

4. Chronic inflammation due to late foreign body

reactions and polymer hypersensitivity

5. Positive remodeling with strut malapposition

6. Strut fracture

7. Neoatherosclerosis


6-mo Taxus

%NC 8%

%DC 2%

9-mo Taxus

%NC 28%

%DC 8%

22-mo Taxus

%NC 39%

%DC 20%

48-mo BMS

%NC 40%

%DC 25%

57-mo BMS

%NC 57%

%DC 15%

Neoatherosclerosis: Transformation of Neointimal

Hyperplasia to Necrotic Core in BMS and DES

Kang SJ et al. AJC 2010;106:1561-1565


Three Approaches to Improve Late

DES Outcomes

1. Metallic DES with bioabsorbable polymers

2. Metallic DES, polymer-free

3. BioResorbable vascular scaffolds (BVS)


Stefanini GG et al. EHJ 2012;33:1214–22

Ste

nt

thro

mb

os

is (

%)

2

0

0

3

4

5

HR (95% CI) DP BP

ISAR-TEST 3 1/202 2/202

ISAR-TEST 4 9/1299 10/652

LEADERS 20/857 32/850

Overall 30/2358

0.47 (0.04, 5.04)

0.45 (0.18, 1.12)

0.62 (0.35, 1.08)

44/1704 0.56 (0.35, 0.90)

0.1

Favors BP HR

10

Favors DP

0.22 [0.08, 0.61]

P=0.004

0.02 [0.47, 1.38]

P=0.43

1 2 3 4

1

Ste

nt

thro

mb

os

is (

%)

Years

2

0

0

3

4

5

HR [95%CI] = 0.56 [0.35, 0.90]

P=0.015

1 2 3 4

1

Biodegradable polymer Durable polymer

Years

Test for heterogeneity P=0.84

Test for inconsistency 12=0%

Test for overall effect z2=2.43 (P=0.015)

Meta-analysis of Bioresorbable Polymer DES:

ISAR-TEST 3, ISAR-TEST 4, and LEADERS at 4 yrs

4,062 randomized pts assigned to bioresorbable polymer

eluting sirolimus or biolimus A (2,388) or Cypher (1,704)

Definite Stent Thrombosis

1.3%

2.8%


Abluminal Bioabsorbable Polymer

SYNERGY Stent (BSC)

Abluminal bioabsorbable

polymer (PLGA)

3-4 um thick

Thin PtCr stent

(74 – 81 um)

PLGA bioabsorbable

polymer + everolimus on

abluminal side of stent

Coating weight on 16 mm

stent ~200 µg (vs ~685 µg

for Xience / Promus)

Everolimus elutes over

~3 months (similar to

Xience / Promus)

PLG undetectable by

~4 months, leaving

behind a BMS


291 Pts Randomized to

Promus Element vs. Synergy vs Synergy ½ dose Primary Endpoints

Meredith I et al. JACC 2012;59:1362–70

P=0.19

Late Loss at 6 Months TLF at 30 Days

La

te lo

ss, m

m

0.0

0.5

0.6

PROMUS

Element

SYNERGY SYNERGY

½ Dose

P=0.56

0.4

0.3

0.2

0.1

0.15 0.10 0.13

P=0.49

Targ

et

lesio

n f

ail

ure

, %

0.0

8.0

10.0

PROMUS

Element

SYNERGY

P=0.25

6.0

4.0

2.0

0

1.1

3.1

SYNERGY

½ Dose


EVOLVE II Study Design SYNERGY Stent Pivotal Trial

Randomized cohort (RCT)

SYNERGY

N=842

PROMUS Element

N=842

RCT Design

Multicenter noninferiority trial

Single-blind, 1:1 randomization

Primary Endpoint: TLF (CD, TV-MI, or TLR) at 12 mo

Follow-up: 30d, 6m, 12m, 18m and annual 2-5 yrs

1,954-2,006 pts with native coronary lesions ≤34 mm in length, RVD ≥2.25 mm - ≤4.0, %DS ≥50%

Up to 3 lesions in 2 vessels

(excludes LM disease, CTO, ISR, STEMI)

SYNERGY

N=250-292

SYNERGY

N=20-30

Diabetes

Substudy

PK

Substudy

Up to 160 global sites

Enrollment Complete


Selectively micro-structured surface holds

drug in abluminal surface structures

BioFreedom Stent (Biosensors) Hypothesis: Polymer-free drug

release via porous-eluting

stents may reduce late events

caused by polymer stent

coatings.

Potential advantages

• Avoid long term late adverse

effects that might be attributable to

the polymer

• Improved surface integrity since

there is no polymer to be sheared

or pealed away from the stent

struts

• Possible shorter need of dual

antiplatelet therapy

Biolimus A9 - lipophilic


DFS: Drug Filled Stent (Medtronic)

Drug elution controlled by diffusion physics

Elution Holes


Bioresorbable Vascular Scaffolds (BRS)

Igaki-Tamai PLLA

Magnesium

(eluting sirolimus) Biotronik Dreams

PLLA

(eluting everolimus) Abbott Absorb

Reva ReSolve Iodinated tyrosine-

derivative

(eluting sirolimus)

Elixir DESolve PLLA

(eluting novolimus)


Igaki-Tamai Stent (2000)

Hideo Tamai, MD Died 14 Feb, 2009


A

B

C

C

B

A

D

D

E

E

I-T stent

@10

Years!

Onuma Y et al. EuroInt 2009


Mass L

os

s (

%)

BVS Resorption: Molecular Weight and Mass Loss

Resorption by 36 Months in Porcine Coronary Model

Images and data on file with Abbott Vascular

1 month 12 months 18 months 24 months 30 months 36 months 42 months

Mo

lecu

lar

Weig

ht

(%)

Months

100

80

60

40

20

0 0 6 12 18 24 30 36 42

Limit of measurement

Months

100

80

60

40

20

0 0 6 12 18 24 30 36 42 48


BVS: Restoration of Pulsatility in the Porcine

Coronary Model

Data on file, Abbott Vascular

Δ D

iasto

le-S

ys

tole

Lu

me

n A

rea

Months

BVS

EES

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

1 3 6 12 18 24 30 36 42


ABSORB: Vasomotion Restoration Restoring Natural Vessel Function

1,2Serruys PW. ACC 2011; 3Serruys PW et al. Lancet 2009;373:897-910

in

Vessel

Dia

mete

r (m

m)

-1.0

-0.5

0.0

0.5

1.0

(N = 15)

6 Months1

(N = 6) (N = 19)

12 Months2

(N = 13) (N = 9)

24 Months3

(N = 7)

Vaso

dilati

on

V

aso

co

nstr

icti

on

Cohort B1 Cohort B2 Cohort A

(pre

-dru

g infu

sio

n t

o p

ost-

dru

g infu

sio

n)

Methergine

Acetylcholine


Cu

mu

lati

ve f

req

ue

nc

y d

istr

ibu

tio

n (

mm

)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-0,75 -0,5 -0,25 0 0,25 0,5 0,75 1 1,25 1,5 1,75 2

Late loss (mm)

6 month (SPIRIT II): 0.17 ± 0.32 mm (N=97)


Claessen BE et al. Circ CV Int. 2009;2:339-47

Late Loss with Absorb Cohort B vs. Xience V


Cu

mu

lati

ve f

req

ue

nc

y d

istr

ibu

tio

n (

mm

)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-0,75 -0,5 -0,25 0 0,25 0,5 0,75 1 1,25 1,5 1,75 2

Late loss (mm)

Late Loss with Absorb Cohort B vs. Xience V



6 month (Cohort B): 0.19 ± 0.18 mm (N=42)

24 month (Cohort B): 0.27 ± 0.20 mm (N=38)

Claessen BE et al. Circ CV Int. 2009;2:339-47

Serruys PW. ESC 2012


BL 1Y

3Y

5Y

• At baseline, the scaffold shields the vessel wall from wall stress (Lancet 2009)

• During the first year, thick struts generating low shear stress serve as a template for neointimal formation

• At 3 years, neointimal growth has been fully compensated by the outward shift of malleable remnants of the scaffold, so that the lumen late loss remains unchanged.

100

40

70

80

90

60

50

0.6 1.2 1.8 2.4

30

20

10

0

0 -0.6

1Y cohort B

• At 4 and 5 years, vessel wall thinning ( ± plaque-media reduction) will result in progressive late lumen enlargement

3Y cohort B

2 Year 3 Year 4 Year

c/o Serruys PW


Months

mm2

6

6,5

7

7,5

8

8,5

9

0 6 12 18 24 30 36

B2

Δ- 0.31mm2

P=0.004

Δ+0.73 mm2

P<0.0001

Δ+0.46mm2

P=0.0006

Δ+0.58mm2

P=0.0002

Cohort B2: Serial Quantitative IVUS (n=45)

Mean Scaffold Area Mean Lumen Area Total Plaque Area

Serruys PW et al.

EuroInt 2014


%

mm2

0

10

20

30

40

50

60

70

80

90

100

0 5 10 15 20 25

Plaque

Mean Vessel area at 18 months Mean Vessel area at 60 months

Mean Plaque area at 18 months Mean Plaque area at 60 months

Mean Lumen area at 18 months Mean Lumen area at 60 months

Lumen = Vessel

Cohort A: CFD Curves of Vessel Area, Plaque Area

and Lumen Area on MSCT at 18 and 60 Months

Onuma Y et al. JACC CV Int 2013;6:999–1009


Vessel area (mm2) 15.72 15.34 14.09 13.76

Mean lumen area (mm2) 6.95 6.17 6.56 8.09

Plaque area (mm2) 8.78 9.17 7.54 7.07

Interventional Plaque Regression by BVS:

Substantial lumen enlargement due to plaque

regression with adaptive remodeling (cohort A pt)

Pre-PCI Post-PCI 6 months 2 years 5 years

c/o Patrick Serruys


ABSORB III + IV

A clinical program consisting of

2 integrated randomized trials designed to:

1) Achieve approval of ABSORB in the US

and

2) Demonstrate superiority of ABSORB

compared to best in class DES

ABSORB III: 2,000 randomized pts (enrolled)

ABSORB IV: 3,000 randomized pts (to begin soon)


Conclusions: Current and future

directions in stenting

• Current DES have appreciably improved safety and

efficacy profiles in ACS and stable CAD compared to

first generation devices

• By utilizing small amounts of a bioabsorbable polymer,

polymer-free systems, or fully bioresorbable scaffolds,

future generation DES will likely further reduce stent

thrombosis and improve late outcomes

• If clinical trials prove that BRS reduce very late events

from 1-5 years and/or stabilize or regress plaque, the

4th revolution in IC will have arrived!

the evolution of pci - stents - solaci

Documents