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Stents Coronarios Cundo, cmo y por qu segn la situacin clnica?

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 investigacin


Cordis, Eurocor

Programas de entrenamiento y educacin


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

BENESTENT II study trial


% 35 30 25 20 15 10 5 0
48% *

STENT BALOON
27% * 37% *

Restenosis

TVR

MACE

Restenosis prediction
60 50 40 30 20 10 0 2,5 2,75 3 3,25 3,5 3,75 8
15 18 25 28 35

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

WHAT DOES IT MEANS DRUG ELUTING STENT?

PLATFORM

DRUG

POLYMER

NEW CONCEPT IN ENDOVASCULAR THERAPEUTIS


Inflammation Thrombosis Migration Proliferation

Reestenosis versus Stent tamao de vaso y largo de lesin


60
Restenosis %

60 50 40 30

Zona Sirolimus 60 50 + diabetes 50


Restenosis %
Restenosis %

Alta Probabilidad 20
10 0

dimetro 2.75 mm

2.76 3.2 mm
dimetro 3.3 mm

Sirolimus
30
Restenosis %
60 50

40

40 30 20 10 0

Longitud 10 mm

Vasos 2.75 mm Mehran R. AHA 1997


dimetro <2.5 mm

10-15 mm

>15 mm

20 10 0

40 30 20 10

2.5 3.0 mm dimetro >3.0 mm

Longitud <12 mm

Vasos 3.3 mm

12-15 mm

>15 mm
Leon M. SIRIUS. TCT2002

10 mm 0
Longitud <12 mm

10-15 mm

dimetro <2.5 mm dimetro >3.0 mm

2.5 3.0 mm

>15 mm
Mehran R. AHA 1997

Largo 12-15 mm de lesion >15 mm


Leon M. SIRIUS. TCT2002

Liberal vs. Selective DES Use

Clinical Outcomes: Death or MI


Death
Liberal DES use Selective DES use

Death or MI
Liberal DES use Selective DES use

Plogrank = 0.30

Plogrank = 0.99

2.9% 2.5%

4.6% 4.6%

Liberal vs. Selective DES Use

Clinical Outcomes: Repeat Revasc.


TLR
Plogrank = 0.03 Plogrank = 0.07
6.5 % 5.6 %

TVR

5.1% 4.1%

Any Revasc 10.6% 10.1% Liberal DES use Selective DES use

Proposed Guidelines for DES Use


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

NICE (UK)
Any one of the following Vessel diameter <3.0 mm Lesion length >15 mm

Ontario
Diabetes plus Lesion length >20 mm OR Vessel diam 2.75 mm

Implications of Guidelines for DES Utilization: Ontario


Tech Assessment

Characteristic Diabetes (A) Vessel diameter <=2.75 mm (B) Lesion length >20 mm Diabetes + (A or B)

Proportion of Lesions 35.2% 39.1% 18.9% 18.7%

n = 3310 lesions
Lesion-Based Analysis

Implications of Guidelines for DES Utilization: NICE


Guidance

Characteristic Vessel diameter <3.0 mm Lesion length >15 mm Either of the above

Proportion of Lesions 42.1% 36.4% 61.8%

Lesion-Based Analysis

Implications of Guidelines for DES Utilization:


Washington State

Characteristic Stent diameter <3.0 mm Stent length >15 mm Treatment of ISR Diabetes Treatment of unprotected LM Any characteristic
n=13,945 lesions

Proportion of Lesions 74.0% 70.2% 6.6% 34.6% 0.8% 93.4%

Lesion-Based Analysis

MEGAMETANALISIS

Target-vessel revascularization
Study type RCT: all RCT: on-label RCT: off-label Registries
*Random-effects model

Patients, n Trials, n Relative risk 7291 4618 2673 73 819 16 9 8 17 0.45 0.53 0.38 0.53

P* <0.001 <0.001 <0.001 <0.001

47 to 62%

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

MEGAMETANALISIS

MI
Study type RCT: all RCT: on-label RCT: off-label Registries
a. Fixed-effects model b. Random-effects model

Patients, n Trials, n Relative risk 8850 4318 4532 129 955 20 9 12 24 0.94 1.03 0.77 0.89

p 0.54a 0.82a 0.19b 0.023b

23% 11%

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

MEGAMETANALISIS

All-cause mortality
Study type RCT: all RCT: on-label RCT: off-label Registries Patients, n Trials, n Relative risk 8867 4818 4049 161 232 21 10 12 28 0.97 1.05 0.84 0.80 p 0.72a 0.69a 0.24a <0.001b

20%

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

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

Wake Forest University


N of Strata Cinical presentation Elective ACS non MI MI 7 days Age < 64 years 64 years Gender Female Male Heart failure class 1 or 2, no CHF 3 or 4 Hx renal failure No Yes Diabetes mellitus No Yes Lesions stented Single Multiple Stented length 18mm > 18mm Bifurcation No Yes Procedure indication On-label Off- label OVERALL 635 720 847 1050 1152 749 1453 1877 325 2077 117 1494 701 1464 738 941 1261 1992 210 499 1703 2202 48 (15) 51 (14) 85 (21) 54(11) 130 (22) 67 (18) 117 (18) 139 (15) 45 (28) 159 (15) 25 (48) 89 (12) 95 (27) 106 (15) 78 (22) 107(17) 77 (18) 167(17) 17 (16) 26 (10) 158 (19) 184 (17) 31 (10) 45 (12) 80 (18) 58 (11) 98 (17) 47 (12) 109 (15) 121 (13) 35 (21) 134 (13) 20 (31) 93 (12) 61 (17) 86 (12) 70 (18) 39 (13) 117 (14) 139 (14) 17 (17) 11 (5) 145 (16) 156 (14) Patients N (%) Non Fatal MI or Death BMS DES

Non fatal MI or death


Hazard Ratio

DES better

BMS better

(95% CI) 0.63 (0.40-1.00) 0.84 (0.56-1.25) 0.77 (0.57-1.04) 0.92 (0.63-1.33) 0.72 (0.56-0.94) 0.60 (0.42-0.87) 0.87 (0.67-1.13) 0.80 (0.63-1.02) 0.63 (0.41-0.99) 0.78 (0.62-0.98) 0.50 (0.28-0.90) 0.96 (0.72-1.28) 0.58 (0.42-0.80) 0.76 (0.57-1.01) 0.77 (0.56-1.06) 0.74 (0.51-1.07) 0.75 (0.57-1.01) 0.74 (0.59-0.93) 1.03 (0.52-2.01) 0.47 (0.23-0.95) 0.78 (0.62-0.96) 0.77 (0.62-0.95)

28%

37% 50% 42% 23%

0.1

10

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

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.

Death, MI, Ischemia-driven TVR


Primary End Point at 12 month
15

SES

ZES

PES

14.2%

Cumulative Incidence (%)

P<0.0003
10.1%

10

P=0.25
8.3%

SES vs. PES <0.001 Overall P <0.001


0 30 60 90
827 816 821

120

150

180
816 813 808

210

240 270
790 802 763

300

330 360
782 792 745

No. at ZES SES PES

Risk 883 878 884

Follow-Up (Days)

Death or MI
SES
15

ZES

PES

Cumulative Incidence (%)

ZES vs. SES = 0.32 ZES vs. PES = 0.11 SES vs. PES =0.56 Overall P=0.28 7.6% 7.0% 5.8%

0
No. at ZES SES PES Risk 883 878 884

30

60

90

120

150 180

210 240 270 300

330 360

Follow-Up (Days)
828 817 821 824 814 815 820 811 808 820 804 803

Ischemic driven TLR


SES
10

ZES

PES

Cumulative Incidence (%)

SES vs. PES <0.001 Overall P <0.001


5

7.6% P=0.005 4.9% P<0.001 1.4%

0 0
No. at ZES SES PES Risk 883 878 884

30

60

90

120

150 180

210 240 270 300

330 360

Follow-Up (Days)
868 869 875 857 866 861 829 853 813 822 845 794

Ischemic driven TVR


SES
10

ZES

PES

Cumulative Incidence (%)

SES vs. PES <0.001 Overall P <0.001

7.7% P=0.005

5.2% P<0.001 1.9%

0 0
No. at ZES SES PES Risk 883 878 884

30

60

90

120

150 180

210 240 270 300

330 360

Follow-Up (Days)
868 869 875 857 866 861 827 851 812 819 841 793

Strut Level Analysis: Malapposition


Total strut thickness + of the blooming Strut blooming

Strut Polymer

Malapposed distance

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

25 20 15 10 5 0

Malapposed Uncovered p<0.001


p<0.001 p<0.001 p<0.001 p=0.02 7.911.3 6.0 1.9 2.34.1 1.6 0.7 0.010.05 0.01 0.001 0.52.2 0.3 0.2

SES

PES

ZES

BMS

Stent Thrombosis
ARC Any Criteria
3

SES

ZES

PES

Cumulative Incidence (%)

SES vs. PES = 0.01 Overall P =0.048

1.0% 0.8% 0.1%

P=0.62 P=0.03

0 0
No. at ZES SES PES Risk 883 878 884

30

60

90

120

150

180

210

240

270

300

330

360

Follow-Up (Days)
869 869 875 866 867 868 861 863 859 861 857 853

Strut Level Analysis Frequency Distribution of Strut-Lumen Distance


%

50 40 30 20 10 0

Cypher

Taxus

Endeavor

BMS

p<0.001

-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

Strut-Lumen Distance (mm)


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

Angina progresiva Dislipidemia IHSS

71 aos

SES 2.5 x 33 14 atm

SES 2.5 x 28

SES 2.5 x 28 14 atm

Balon 2.5x 15 12 atm

SES 2.5 x 18 Balon 3.0 x 33 10 atm

# S.F. 71 y/o

HOSPITAL

daniel.berrocal@hospitalitaliano.rg.ar

ITALIANO

Buenoss Aires - ARGENTINA

Conclusiones
En escenarios clnicos y anatmicos FAVORABLES BMS En escenarios clnicos y anatmicos ADVERSOS DES EQUILIBRAR CON RIESGO HEMORRAGICO NO TODOS LOS DES SO IGUALES

ZES 2.5 x 18

42 aos

ACS Dbt I Dislipidemia Antecedentes familiares

ZES 3.0 x 30

3 meses

SES 3.0 x 30

Hoye et al.

MACE*
*MI, cardiac death and clinically driven TVR
Bifurcation Group BES vs. SES
Sirolimus Bifurcation group Biolimus Bifurcation group Sirolimus Non-bifurcation group Biolimus Non-bifurcation group

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

HORIZONS AMI All-Cause Mortality

HORIZONS AMI Stent thrombosis

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


Cumulative incidence of cardiac death (%) 5 10 15 20
20

Cmulative incidence of death (%) 15 5 10

Death
p=0,21

Cardiac death
p=0,04

6 Months of Follow-up stent = BES

9 stent = SES

12

6 Months of Follow-up stent = BES

9 stent = SES

12

20

20

p=0,07

Cumulative incidence of MACE (%) 5 10 15

Cumulative incidence of TVR (%) 10 15 5

TVR

MACE
p=0,01

6 Months of Follow-up stent = BES

9 stent = SES

12

6 Months of Follow-up stent = BES

9 stent = SES

12

Six Month OCT Analysis: 75/76 eligible patients


Analyzed: 250 stented segments every 0.3 mm (6968 cross-sections) , 53.047 strutsOLP Distal Pro
x

Ospedali Riuniti di Bergamo

Quantitative Strut Level Analysis


Semi-Automated delineated contours at radial 1degree increments
Lumen Area, Stent Area, Strut -Lumen distance Strut-wall Distance

Inter-observer variability: 39 frames, 333 struts R= 0.997 Observer 1 Strut-Lumen distance 0.380.03 Observer 2 0.380.03 Delta 0.00 SD

0.02

Invasive vs. Conservative in NSTEMI Very early PCI in ACS .4


LOG (OR) FOR DEATH OR MI P= .011 LOG (OR) FOR DEATH OR MI
Early invasive worse

.4
P= .005

.2 0.0
Early invasive better

.2
Early invasive worse

0.0
Early invasive better

-.2 -.4 -.6 -.8


NO STENTING STENTING

-.2 -.4 -.6 -.8


NO AGRESSIVE ANTITHROMBOTIC THERAPY AGRESSIVE ANTITHROMBOTIC THERAPY

Meta-regression. Am Heart J 2005

DES vs. BMS in NSTEMI CVD/MI/CVA


HR 0.81 (0.72-0.90) p=0.0001
16 14 12 10 8 6 4 2 0 A ny B MS DE S 11.9 9.7 12.2 10

Key Efficacy, Safety EP: Stratified by Stent Type

TRITON/TIMI 38

Major Bleeding
HR 0.82 (0.69-0.97) p=0.02
16 14
11.1 9

HR 0.80 (0.69-0.93) p=0.003

CLOPIDOGREL PRASUGREL

12 10 8 6 4 2 0 A ny B MS DE S

HR 1.27 (0.99-1.63) p=0.06


1.9 2.4

HR 1.37 (0.95-1.99) p=0.09


1.6 2.3

HR 1.19 (0.83-1.72) p=0.34


2.1 2.5

N=12844

N=6461

N=5743

DES for AMI Metanalysis (n= 2357 p)


MACE at 8-12 months 43%
25

RR=0.53 p<0.0001
17,6

DES (n=1177) BMS (n=1180)


RR=0.40 p<0.0001 p=NS
12

20

p=NS
15 9,3 10 5,8 5 6,9

p=NS

4,8 2,8 3,1 2,3 2,6

Death-MI-TLR

Death-MI

Non fatal MI

TLR

Stent thrombosis

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

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

Death
SES
5

ZES

PES

Cumulative Incidence (%)

ZES vs. SES = 0.77 ZES vs. PES = 0.32 SES vs. PES = 0.48 Overall P =0.57

1.1%
1

0.8% 0.7%
0 30 60 90 120 150 180 210 240 270 300 330 360

No. at ZES SES PES

Risk 883 878 884

Follow-Up (Days)
871 869 880 869 867 873 864 863 865 864 857 859

MI
SES
15

ZES

PES

Cumulative Incidence (%)

ZES vs. SES = 0.40 ZES vs. PES = 0.12 SES vs. PES =0.45 Overall P =0.30 7.0% 6.3%

5.3%

0
No. at ZES SES PES Risk 883 878 884

30

60

90

120

150 180

210 240 270 300

330 360

Follow-Up (Days)
828 817 821 824 814 815 820 811 808 820 804 803

Stent Thrombosis
: ARC Definite Criteria
3

SES

ZES

PES

Cumulative Incidence (%)

SES vs. PES = 0.02 Overall P =0.06

0.7% 0.5%
0 0 30
Risk 883 878 884

P=0.53 P=0.046

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

Follow-Up (Days)
No. at ZES SES PES 869 869 875 866 867 868 861 863 859 861 857 853

Stent Thrombosis
: ARC Definite or Probable Criteria
3

SES

ZES

PES

Cumulative Incidence (%)

SES vs. PES = 0.008 Overall P = 0.037

0.8% 0.7% 0%
0 30 60 90 120 150 180 210 240 270 300 330 360

P=0.79 P=0.02

Follow-Up (Days)
No. at ZES SES PES Risk 883 878 884 869 869 875 866 867 868 861 863 859 861 857 853

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

%
p<0.001

p<0.001

p<0.001 p=0.04 8.713.3 5.8 2.9 8.320.9 2.7 5.5 0.050.19 0.02 0.04 1.84.0 1.8