Stents Coronarios Cuándo, cómo y por qué

según la situación clínica?

Daniel Berrocal, MD, FACC Jefe de Cardiologia Intervencionista daniel.berrocal@hiba.org.ar

Conflicto de intereses

Conferencista Boston Scientific, Biosensors, Cordis, Terumo

Asesor Cordis

Fondos para investigación Cordis, Eurocor

Programas de entrenamiento y educación Biosensors, Cordis, Terumo

Que problemas queremos resolver con los stents? Cobertura y soporte mecanico de la placa Recrear el lumen mas grande posible Contener disecciones Prevenir oclusiones agudas Reducir la reestenosis

Que problemas podemos provocar con los stents? Trombosis Riesgo hemorragico

05

101520253035

Restenosis TVR MACE

48% ↓*

37% ↓*

27% ↓*

BENESTENT II study trial % STENT

BALOON

Restenosis prediction

0102030405060

2,5 2,75 3 3,25 3,5 3,75 815

1825

2835

Diameter

Kereiakes D et al. Usefulness of stent length in predicting in-stent restenosis (the MULTI-LINK stent trials). Am J Cardiol 2000 Aug 1;86(3):336-41

PLATFORM DRUG POLYMER

WHAT DOES IT MEANS DRUG ELUTING STENT?

Inflammation Thrombosis Migration Proliferation

NEW CONCEPT IN ENDOVASCULAR THERAPEUTIS

Reestenosis versus tamaño de vaso y largo de lesión

0

10

20

30

40

50

60

10 mm 10-15 mm >15 mm

Rest

enos

is %

Mehran R. AHA 1997

Largo de lesion

Vasos ≥3.3 mm

Vasos ≤2.75 mm

Zona Alta Probabilidad

0

10

20

30

40

50

60

10 mm 10-15 mm >15 mm

Rest

enos

is %

diámetro ≥3.3 mm

diámetro ≤2.75 mm

2.76 – 3.2 mm

Longitud

Stent

Mehran R. AHA 1997

0

10

20

30

40

50

60

<12 mm 12-15 mm >15 mm

Rest

enos

is %

diámetro >3.0 mm

diámetro <2.5 mm 2.5 – 3.0 mm

Longitud

Sirolimus

Leon M. SIRIUS. TCT2002

0

10

20

30

40

50

60

<12 mm 12-15 mm >15 mm

Rest

enos

is %

diámetro >3.0 mm

diámetro <2.5 mm 2.5 – 3.0 mm

Longitud

Sirolimus + diabetes

Leon M. SIRIUS. TCT2002

Clinical Outcomes: Death or MI

Death Death or MI

Liberal DES use Selective DES use

Liberal DES use Selective DES use

2.5%

2.9%

Plogrank = 0.30 Plogrank = 0.99

Liberal vs. Selective DES Use

4.6% 4.6%

Clinical Outcomes: Repeat Revasc.

Any Revasc

10.6% 10.1%

TLR

5.1% 4.1%

Plogrank = 0.03

TVR

6.5% 5.6%

Plogrank = 0.07

Liberal DES use Selective DES use

Liberal vs. Selective DES Use

Proposed Guidelines for DES Use

Any one of the following

• Vessel diameter <3.0 mm

• Lesion length >15 mm

NICE (UK)

Diabetes plus

• Lesion length >20 mm

OR

• Vessel diam ≤2.75 mm

Ontario Washington State

Any one of the following

• Stent diameter ≤ 3.0 mm

• Stent length ≥ 15 mm

• Treatment of in-stent restenosis

• Diabetes

• Unprotected LM stenosis

Implications of Guidelines for DES Utilization: Ontario Tech Assessment

Characteristic Proportion of Lesions

Diabetes 35.2%

(A) Vessel diameter <=2.75 mm 39.1%

(B) Lesion length >20 mm 18.9%

Diabetes + (A or B) 18.7%

Lesion-Based Analysis

n = 3310 lesions

Implications of Guidelines for DES Utilization: NICE Guidance

Characteristic Proportion of Lesions

Vessel diameter <3.0 mm 42.1%

Lesion length >15 mm 36.4%

Either of the above 61.8%

Lesion-Based Analysis

Implications of Guidelines for DES Utilization: Washington State

Characteristic Proportion of Lesions

Stent diameter <3.0 mm 74.0%

Stent length >15 mm 70.2%

Treatment of ISR 6.6%

Diabetes 34.6%

Treatment of unprotected LM 0.8%

Any characteristic 93.4%

Lesion-Based Analysis n=13,945 lesions

Kirtane AJ, Stone GW. Comprehensive meta-analysis of DES vs BMS randomized trials and registries; March 28, 2008; Chicago, IL.

Target-vessel revascularization Study type Patients, n Trials, n Relative

risk P*

RCT: all 7291 16 0.45 <0.001 RCT: on-label 4618 9 0.53 <0.001 RCT: off-label 2673 8 0.38 <0.001 Registries 73 819 17 0.53 <0.001 *Random-effects model

MEGAMETANALISIS

47 to 62%

Kirtane AJ, Stone GW. Comprehensive meta-analysis of DES vs BMS randomized trials and registries; March 28, 2008; Chicago, IL.

MI Study type Patients, n Trials, n Relative

risk p

RCT: all 8850 20 0.94 0.54a RCT: on-label 4318 9 1.03 0.82a RCT: off-label 4532 12 0.77 0.19b Registries 129 955 24 0.89 0.023b a. Fixed-effects model b. Random-effects model

MEGAMETANALISIS

11%

23%

Kirtane AJ, Stone GW. Comprehensive meta-analysis of DES vs BMS randomized trials and registries; March 28, 2008; Chicago, IL.

All-cause mortality Study type Patients, n Trials, n Relative

risk p

RCT: all 8867 21 0.97 0.72a RCT: on-label 4818 10 1.05 0.69a RCT: off-label 4049 12 0.84 0.24a Registries 161 232 28 0.80 <0.001b

a. Fixed-effects model b. Random-effects model

MEGAMETANALISIS

20%

DES better BMS better

Applegate et al. JACC: 51. 6; 607-614 Februaru2008

0.1 1 10

Wake Forest University

28%

37%

50%

42%

23%

Non fatal MI or death N° (%) Non Fatal N° of MI or Death Hazard Ratio Strata Patients BMS DES (95% CI) Cinical presentation Elective 635 48 (15) 31 (10) 0.63 (0.40-1.00) ACS non MI 720 51 (14) 45 (12) 0.84 (0.56-1.25) MI ≤ 7 days 847 85 (21) 80 (18) 0.77 (0.57-1.04) Age < 64 years 1050 54(11) 58 (11) 0.92 (0.63-1.33) ≥ 64 years 1152 130 (22) 98 (17) 0.72 (0.56-0.94) Gender Female 749 67 (18) 47 (12) 0.60 (0.42-0.87) Male 1453 117 (18) 109 (15) 0.87 (0.67-1.13) Heart failure class 1 or 2, no CHF 1877 139 (15) 121 (13) 0.80 (0.63-1.02) 3 or 4 325 45 (28) 35 (21) 0.63 (0.41-0.99) Hx renal failure † No 2077 159 (15) 134 (13) 0.78 (0.62-0.98) Yes 117 25 (48) 20 (31) 0.50 (0.28-0.90) Diabetes mellitus ‡ No 1494 89 (12) 93 (12) 0.96 (0.72-1.28) Yes 701 95 (27) 61 (17) 0.58 (0.42-0.80) Lesions stented Single 1464 106 (15) 86 (12) 0.76 (0.57-1.01) Multiple 738 78 (22) 70 (18) 0.77 (0.56-1.06) Stented length ≤ 18mm 941 107(17) 39 (13) 0.74 (0.51-1.07) > 18mm 1261 77 (18) 117 (14) 0.75 (0.57-1.01) Bifurcation No 1992 167(17) 139 (14) 0.74 (0.59-0.93) Yes 210 17 (16) 17 (17) 1.03 (0.52-2.01) Procedure indication On-label 499 26 (10) 11 (5) 0.47 (0.23-0.95) Off- label 1703 158 (19) 145 (16) 0.78 (0.62-0.96) OVERALL 2202 184 (17) 156 (14) 0.77 (0.62-0.95)

Cumulative Incidence of Cardiac Death

Stettler C., et al., Lancet 2007;370:937-48.

Cumulative Incidence of TLR

TVR was used as a proxy for 3 studies Stettler C., et al., Lancet 2007;370:937-48.

Cumulative Incidence of ARC Definite Stent Thrombosis

Stettler C., et al., Lancet 2007;370:937-48.

Primary End Point at 12 month Death, MI, Ischemia-driven TVR

No. at Risk ZES 883 827 816 790 782 SES 878 816 813 802 792 PES 884 821 808 763 745

14.2%

10.1%

8.3%

ZES SES PES

SES vs. PES <0.001 Overall P <0.001

15

10

5

0 30 60 90 120 150 180 210 240 270 300 330 360 Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

P=0.25

P<0.0003

ZES vs. SES = 0.32 ZES vs. PES = 0.11 SES vs. PES =0.56

Overall P=0.28 7.6%

5.8%

7.0%

15

5

0 30 60 90 120 150 180 210 240 270 300 330 360 Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

No. at Risk ZES 883 828 824 820 820 SES 878 817 814 811 804 PES 884 821 815 808 803

Death or MI ZES SES PES

No. at Risk ZES 883 868 857 829 822 SES 878 869 866 853 845 PES 884 875 861 813 794

7.6%

4.9%

1.4%

SES vs. PES <0.001 Overall P <0.001

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

) 10

5

0 30 60 90 120 150 180 210 240 270 300 330 360 0

Ischemic driven TLR ZES SES PES

P<0.001

P=0.005

No. at Risk ZES 883 868 857 827 819 SES 878 869 866 851 841 PES 884 875 861 812 793

7.7%

5.2%

1.9%

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

) 10

5

0 30 60 90 120 150 180 210 240 270 300 330 360 0

Ischemic driven TVR ZES SES PES

P<0.001

P=0.005

SES vs. PES <0.001 Overall P <0.001

Strut

Polymer

Total strut thickness + ½ of the blooming

Strut Level Analysis: Malapposition

Malapposed distance

Strut blooming

0

5

10

15

20

25

SES PES ZES BMS

Malapposed Uncovered

1.9

6.0

0.7 0.001 0.01

0.2

7.9±11.3

2.3±4.1 0.01±0.05 0.5±2.2

p<0.001

p=0.02

p<0.001

p<0.001 p<0.001

Non-overlap Proportion of uncovered and/or malapposed struts by stent type

1.6 0.3

%

SES vs. PES = 0.01 Overall P =0.048

1.0% 0.8%

0.1%

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

3

2

0 30 60 90 120 150 180 210 240 270 300 330 360 0

1

No. at Risk ZES 883 869 866 861 861 SES 878 869 867 863 857 PES 884 875 868 859 853

ARC Any Criteria Stent Thrombosis

ZES SES PES

P=0.03

P=0.62

-0,6-0,5-0,4-0,3-0,2-0,1 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 1,1 1,2 1,3 1,4 1,5

Cypher Taxus Endeavor BMS

Strut-Lumen Distance (mm)

0

10

20

30

40

50 %

Strut Level Analysis Frequency Distribution of Strut-Lumen Distance

p<0.001

Based on ANOVA test, Kruskal-Wallis test and generalized linear model with complex sample analysis (clustered )

♂71 años Angina progresiva Dislipidemia IHSS

HOSPITAL ITALIANO Buenoss Aires - ARGENTINA daniel.berrocal@hospitalitaliano.rg.ar # S.F. 71 y/o ♂

SES 2.5 x 33 14 atm

SES 2.5 x 28

SES 2.5 x 28 14 atm

Balon 3.0 x 33 10 atm

Balon 2.5x 15 12 atm

SES 2.5 x 18

Conclusiones

En escenarios clínicos y anatómicos FAVORABLES → BMS

En escenarios clínicos y anatómicos ADVERSOS→ DES

EQUILIBRAR CON RIESGO HEMORRAGICO

NO TODOS LOS DES SO IGUALES

ZES 2.5 x 18

ZES 3.0 x 30 ♀ 42 años ACS Dbt I Dislipidemia Antecedentes familiares

3 meses

SES 3.0 x 30

Hoye et al.

MACE*

Bifurcation Group BES vs. SES HR 0-2 days : 1.62 [0.77-3.40] p=0.20 3-360 days : 0.46 [0.24-0.88] p=0.02

Sirolimus Bifurcation group Biolimus Bifurcation group Sirolimus Non-bifurcation group Biolimus Non-bifurcation group

*MI, cardiac death and clinically driven TVR

HORIZONS AMI All-Cause Mortality

Stent thrombosis HORIZONS AMI

One-Year Cumulative Incidence of Death, Cardiac Death, TVR and MACE

05

1015

20Cu

mula

tive

incide

nce

of M

ACE

(%)

0 3 6 9 12Months of Follow-up

stent = BES stent = SES

05

1015

20Cu

mula

tive

incide

nce

of T

VR (%

)

0 3 6 9 12Months of Follow-up

stent = BES stent = SES

05

1015

20Cu

mul

ative

incid

ence

of c

ardi

ac d

eath

(%)

0 3 6 9 12Months of Follow-up

stent = BES stent = SES

05

1015

20Cm

ulat

ive in

ciden

ce o

f dea

th (%

)

0 3 6 9 12Months of Follow-up

stent = BES stent = SES

Death Cardiac death

TVR MACE

p=0,21 p=0,04

p=0,07 p=0,01

Distal OLP Prox

Ospedali Riuniti di Bergamo

Six Month OCT Analysis: 75/76 eligible patients Analyzed: 250 stented segments every 0.3 mm (6968 cross-sections) , 53.047

struts

Quantitative Strut Level Analysis Semi-Automated delineated contours at radial 1degree increments

Lumen Area, Stent Area, Strut -Lumen distance

Strut-wall Distance

Strut-Lumen distance 0.38±0.03 0.38±0.03 0.00 0.02

Observer 1 Observer 2 Delta SD

R= 0.997

Inter-observer variability: 39 frames, 333 struts

Meta-regression. Am Heart J 2005

.4

.2

0.0

-.2

-.4

-.6

-.8

.4

.2

0.0

-.2

-.4

-.6

-.8

P= .011

Early invasive worse

Early invasive better

Early invasive worse

Early invasive better

LOG

(OR

) FO

R D

EATH

OR

MI

LOG

(OR

) FO

R D

EATH

OR

MI

P= .005

NO STENTING STENTING NO AGRESSIVE ANTITHROMBOTIC THERAPY

AGRESSIVE ANTITHROMBOTIC THERAPY

Very early PCI in ACS

Invasive vs. Conservative in NSTEMI

TRITON/TIMI 38 Key Efficacy, Safety EP: Stratified by Stent Type

CVD/MI/CVA Major Bleeding

11.9 12.211.1

109.79

0

2

4

6

8

10

12

14

16

Any B MS D E S

1.9 1.6 2.1 2.52.4 2.3

0

2

4

6

8

10

12

14

16

Any B MS D E S

HR 0.80 (0.69-0.93) p=0.003

HR 0.81 (0.72-0.90) p=0.0001

HR 0.82 (0.69-0.97) p=0.02

HR 1.37 (0.95-1.99) p=0.09

HR 1.27 (0.99-1.63) p=0.06

HR 1.19 (0.83-1.72) p=0.34

N=12844 N=6461 N=5743

CLOPIDOGREL PRASUGREL

DES vs. BMS

in NSTEMI

Pasceri V. Am Heart J 2007;153:749-754.

4,8

2,32,8

5,8

9,3

12

2,63,1

6,9

17,6

0

5

10

15

20

25

Death-MI-TLR Death-MI Non fatal MI TLR Stentthrombosis

MACE at 8-12 months DES (n=1177) BMS (n=1180) RR=0.53

p<0.0001

p=NS p=NS p=NS

RR=0.40 p<0.0001

DES for AMI

Metanalysis (n= 2357 p)

43%

Cumulative Incidence of All Death

Stettler C., et al., Lancet 2007;370:937-48.

Cumulative Incidence of Myocardial Infarction

Stettler C., et al., Lancet 2007;370:937-48.

SES 2.5 x 18

SES 3.0x 23

SES 2.5 x 13

No. at Risk ZES 883 871 869 864 864 SES 878 869 867 863 857 PES 884 880 873 865 859

1.1%

0.7% 0.8%

ZES vs. SES = 0.77 ZES vs. PES = 0.32 SES vs. PES = 0.48

Overall P =0.57

Death 5

3

1

0 30 60 90 120 150 180 210 240 270 300 330 360

4

2

0

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

) ZES SES PES

No. at Risk ZES 883 828 824 820 820 SES 878 817 814 811 804 PES 884 821 815 808 803

7.0%

5.3%

6.3%

ZES vs. SES = 0.40 ZES vs. PES = 0.12 SES vs. PES =0.45

Overall P =0.30

15

5

0 30 60 90 120 150 180 210 240 270 300 330 360 Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

MI ZES SES PES

3

2

0 30 60 90 120 150 180 210 240 270 300 330 360 0

1

No. at Risk ZES 883 869 866 861 861 SES 878 869 867 863 857 PES 884 875 868 859 853

0.7% 0.5%

SES vs. PES = 0.02 Overall P =0.06

: ARC Definite Criteria

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

0%

Stent Thrombosis

ZES SES PES

P=0.046

P=0.53

0.8% 0.7%

0%

SES vs. PES = 0.008 Overall P = 0.037

: ARC Definite or Probable Criteria

Follow-Up (Days)

Cum

ulat

ive

Inci

denc

e (%

)

3

2

0 30 60 90 120 150 180 210 240 270 300 330 360 0

1

No. at Risk ZES 883 869 866 861 861 SES 878 869 867 863 857 PES 884 875 868 859 853

Stent Thrombosis

P=0.02

P=0.79

ZES SES PES

2.9

5.8

5.5

2.7

0.04 0.02

1.8

%

8.7±13.3 8.3±20.9 0.05±0.19

1.8±4.0

p<0.001

p=0.04

p<0.001

p<0.001

Secondary Endpoint: Overlap Proportion of uncovered and/or malapposed struts by stent type