DES

Bern/Rotterdam Experience

MY CONFLICTS OF INTEREST ARE • Speaker bureau and research support of

- Cordis - Boston Scientific - Medtronic - Abbott - Biotronik

20

67

7 70 0

13

87

0

20

40

60

80

100

Sirolimus-Eluting Stent (N=15) Bare Metal Stents (N=22)

%

Incomplete Neointimal Coverage of Sirolimus-Eluting Stents

Kotani J et al. JACC 2006;47:2108

P<0.001

Incomplete Coverage Complete Coverage

Treatment of RestenosisTogni M, Windecker S, Meier B

Curr Interv Cardiol Rep 3: 306-310, 2001

..... in particular, the risk of late stent thrombosis driven by inhibitory effects on endothelial regrowth, or late toxic effects on vascular cells, may be encountered with stent-based drug delivery .....

4/2002 2003 2004 2005 12/2005 BERN 3 MONTHS 12 MONTHS

CLOPIDOGREL ROTTERDAM 3 MONTHS 6 MONTHS

CLOPIDOGREL

CYPHER TAXUS

SIRTAX POST-SIRTAX

RESEARCH T-SEARCH

Default Use of DES and Duration of Antiplatelet Treatment

N=4,140

Bern

CYPHER N=2,775

TAXUS N=1,365

Complete clinical follow-up

N=7.406

96.4%

Lost to follow-up

N=289

N=4,006

Rotterdam

TAXUS N=2,958

CYPHER N=1,048

April 2002 - December 2005

N=8,146

Patient Cohort and Study Design

Definite Stent Thrombosis With DES: Bern - Rotterdam Cohort Study

Daemen J et al. Lancet 2007, updated with extended follow-up to 4 years 0

.01

.02

.03

.04

.05

Cum

ulat

ive

Inci

denc

e of

ste

nt th

rom

bosi

s

0 1 2 3 4 5Time since PCI in years

95% CI Failure function

Stent thrombosis1.2%

(1.0-1.4) 1.6%

(1.3-1.9) 2.1%

(1.8-2.5) 2.7%

(2.4-3.2) 3.3%

(2.8-3.9)

Benefit Risk

Net Safety Outcome

Death or Myocardial Infarction

Stent thrombosis Reduced restenosis

Does the Benefit Outweigh the Risk?

Long-term Outcome with DES vs. BMS in Sweden

Lagerqvist B et al. N Engl J Med 2007;356:1009-19

•  6,033 pts with DES and 13,738 pts with BMS in 2003 and 2004 from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

•  FU up to 3 yrs based on 1424 deaths and 2463 MIs and adjusted for differences in baseline characteristics

•  One DES was sufficient to belong to the DES group: Mixed group (DES and BMS in one patient) considered DES group

0.00

0.05

0.10

0.15

0.20

0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.00

0.05

0.10

0.15

0.20

0.0 0.5 1.0 1.5 2.0 2.5 3.0

Unadjusted Primary Endpoint Adjusted Primary Endpoint

Cum

ulat

ive

Ris

k of

D

eath

or M

I

Cum

ulat

ive

Ris

k of

D

eath

or M

I

Drug-eluting stent

Bare-metal stent

Drug-eluting stent

Bare-metal stent

No. at Risk BMS 13,735 12,467 12,172 9,295 5,965 3,205 7 DES 6,033 5,547 5,388 3,379 1,676 606 0

No. at Risk BMS 12,880 11,706 11,432 8,665 5,520 2,963 7 DES 5,770 5,307 5,158 3,216 1,608 580 0

P=ns P=ns

y y

0

5

10

15

20

0

Cum

ulat

ive

inci

denc

e, %

Time in months

Early ST

20.3%

Late ST

10.4%

Mortality Following Early and Late ST

0 12 2 0 6 24 18

0

1

2

3

4

5

0 1 2 3 4

Time since PCI in years

Cum

ulat

ive

inci

denc

e, %

PES (3.6%)

SES (2.7%)

Months 1 12 24 36 42

Cumulative incidence SES, % 1.0 1.2 1.7 2.4 2.7 Cumulative incidence PES, % 1.3 1.9 2.5 3.1 3.6

Logrank p-value 0.019

Stent Thrombosis per Stent Type

3.5

Stent Thrombosis per Stent Type

0

1

2

3

4

5

0 1 2 3

Cum

ulat

ive

inci

denc

e, %

3.5

PES Rotterdam

PES Bern SES Bern SES Rotterdam

Time since PCI in years

Months 1 12 24 36 42

Cumulative incidence SES, % 1.0 1.2 1.7 2.4 2.7 Cumulative incidence PES, % 1.3 1.9 2.5 3.1 3.6

Risk of Stent Thrombosis: SES vs PES Kastrati et al. J Am Coll Cardiol 2007

P=0.01

Days 30 365 730 1095 1278

Sirolimus-eluting stent, % 2.1 4.0 6.3 8.1 9.4 Paclitaxel-eluting stent, % 3.2 6.3 8.8 10.5 11.4

0

5

10

15

20 C

umul

ativ

e in

cide

nce,

%

0 1 2 3 Time since PCI in years

Mortality SES vs. PES

4

PES (11,4%)

SES (9,4%)

Thoraxcenter Real World Experience Overall Mortality of BMS, SES and PES at 3 Years

Serruys PW et al. FDA 12/06

Group 0 3 0 9 0 18 0 36 0 72 0 109 5 BMS 228 7 221 1 219 5 217 0 212 6 199 0 186 2 S E S 97 6 95 5 95 1 94 6 93 6 88 8 83 3 P E S 277 6 262 0 253 7 249 9 241 4 143 2 49 1

0 1 8 0 36 0 5 4 0 72 0 9 0 0 109 5

8 0

8 5

9 0

9 5

10 0

92.1%

89.1% 89.1%

SES vs. B M S HR 0.71; 95% CI 0.54 – 0 .92; p=0.008 2

PES vs. B M S HR 1.02; 95% C I 0 . 93 – 1 . 12 ; p = 0 . 6 9

PES v s. SES HR 1 . 47 ; 95% CI 1.13 – 1 .92; p=0.003 7

Bare metal Cypher Taxus

* Logrank Test

6442 patients

13,150 stents

Relationship of Late Loss and Thrombosis

14 days (courtesy Renu Virmani)

Multivariate Analysis for Early ST (<30 days) Variable HR 95% CI Diabetes 1.96 1.18-3.28

Multivariate Analysis for Late ST (>30 days) Variable HR 95% CI ACS at presentation 2.21 1.39-3.51 Age 0.97 0.95-0.99 Sirolimus-eluting stent use 0.60 0.39-0.93

Multivariate Analysis for Very Late ST (>1 year) Variable HR 95% CI ACS at presentation 2.18 1.25-3.79 Age 0.95 0.93-0.97

Antiplatelet Treatment at Time of Stent Thrombosis

87

27

9

59

144

0%

25%

50%

75%

100%

Early StentThrombosis

Late StentThrombosis

No AntiplateletTherapy

Single AntiplateletTherapy

Dual AntiplateletTherapy

P<0.0001

• 38 trials • 18,023 patients

Probability to Be Best

Collaborative Network Meta-Analysis, Stettler C et al. Lancet 2007; 370: 937–48