The use of DES in the setting of AMI

That’s why I would use a DES

Leonardo Bolognese
Cardiovascular Department, Arezzo, Italy
Why should we be concerned about DES in AMI?

May not be necessary

May not be cost-effective

Need to be proven safe

Why should we be concerned about ES in AMI?

May not be necessary

Culprit lesion may be less prone to

restenosis

Recurrent ischemia is infrequente in post

AMI patients

TLR post BMS for AMI is low

Late Loss After bare Metal Stent
In Acute Myocardial Infarction

Plaque rupture
The culprit plaque in AMI
has relatively low plaque
mass and a potentially
lower restenosis rate
 BMS

G
R
A
BMS in

M
FR I1

5%
10%
15%
20%

0%
E S 99 8
C (n
in AMI

O
AMI

Zw 19 =52
)
14%

ol 98
le (n
PR 19 =7
IS
8%

98 5)
A (
M n=
19 11
PA
13%

99 2)
ST (n
PS A =1
19 10
A 9 )
23%

St A 9
en M (n
tP I 19 =6
7)
18%

A 99
ST M (n
EN I1 =4
TI 99
M 9 4)
16%

C -2 (n
A 20 =4
D 52
IL 00
)
11%

LA (n
C =1
20 01
)
17%

Zw 02
ol (n
le =5
20
7%

24
05 )
(n
=8
20%

49
)
arms of randomized trials
6/12-month TVR in the stent
 What about external validity?
Mostly excluded patients:
 In some of these trials randomization t e s
occurred after angiography before i da PCI
Shock
 In some of these studies a n d
Diffusely diseased or small c randomization
coronary
tangioplasty
occurred
vessel after balloon
te n
 In none of these d s
studies patients were
o
Large thrombus o burden
g
recruitedrwithout prior knowledge of
Severel
coronary o
coronary
anatomy calcification or
e a
tortuosity
Id
Bifurcated lesions
 G
RA
M
I1
BMS

FR 99
8

0%
5%
10%
15%
20%
ES
CO (n
=
BMS in

19 52
Zw 98 )
14%
ol (n
le =
19
in AMI

75
PR 9
AMI

IS 8 )
AM (n
= 8%
19 11
99 2)
PA
13%

(n
ST
A =
11
1 9 0)

intervention
PS
AA 9 9
23%

M (n

Randomized after
St I =
en
t 1 67
99 )
PA 9
18%

M (n
ST
EN
I1 =
99 44
TI 9 )
M (
16%

-2 n=
CA 20 45
DI 00 2)
LL (n
11%

AC =1
20 01
02 )
14%

Zw (n
ol =
le 52
4)
intervention

20
7%

05
(n
Randomized before

=
84
9)
20%
arms of randomized trials
6/12-month TVR in the stent
 N=1683

Heart 2005;91:641–645.
Partecipants: All Patients with STEMI randomly
assigned to stenting or balloon Angioplasty.
No exclusion criteria were applied.

RR 0.98 (95%CI: 0.78-1.22)

25 Death or Reinfarction

20
TVR (%)

15
Stent
Balloon
10

0
 Lessons from the BMS era

 BMS in the setting of STEMI is far from being the

perfect solution for restenosis and TVR may
remain high

 New devices are needed which have to be tested in

unselected (no angiographic selection bias) patient
population
Evidence from Randomized Trials
Overview of available RCTs on DES in STEMI
Length of Mean Length of
No. of No. of Patients Mean Age Availability of Individual
Study Type of DES Primary End Point thienopyridine therapy Follow-Up
Patients With Diabetes (years) Patient Data
(months) (months)

Angiographic late
HAAMU-STENT 164 24 63.0 PES Yes 12 16.7
lumen loss

Angiographic late
MISSION 310 30 59.2 SES No 12 12.0
lumen loss

Cardiac death, MI,

PASSION 619 68 61.0 PES Yes 6 12.0
or TVR

2476
SESAMI 320 65 61.6 SES Yes Binary restenosis 12 12.3

Death, MI, stroke,

STRATEGY 175 26 62.6 SES Yes or binary 3 24.2
restenosis

Cardiac death, MI,

TYPHOON 712 116 59.3 SES Yes 6 12.1
or TVR

62.2 Cardiac death,

BASKET-AMI 216 SES/PES Yes 6 18
MI, or TVR

Death, 12
Di Lorenzo et al 270 64 SES/PES Yes 6
MI, or TVR
Meta-analysis of randomized trials on drug-eluting
stents vs. bare-metal stents in patients with AMI

REINTERVENTION
REINTERVENTION

13.1%

5.1%

RRR:
RRR: 61%
61%
Kastrati et al. EHJ (2007) 28, 2706–2713
NNT:
NNT: 13
13
Meta-analysis of randomized trials on drug-eluting
stents vs. bare-metal stents in patients with AMI

Death
Death or
or Reinfarction
Reinfarction

P=0.11

4.0%
3.1%

Kastrati et al. EHJ (2007) 28, 2706–2713

Overview of available RCTs on DES in STEMI
Length of Mean Length of
No. of No. of Patients Mean Age Availability of Individual
Study Type of DES Primary End Point thienopyridine therapy Follow-Up
Patients With Diabetes (years) Patient Data
(months) (months)

Angiographic late
HAAMU-STENT 164 24 63.0 PES Yes
Singlelumen
centre
loss !! 12 16.7

Angiographic late
MISSION 310 30 59.2 SES No
Singlelumen
centre
loss !! 12 12.0

Cardiac death, MI,

PASSION 619 68 61.0 PES Yes 6 12.0
or TVR

SESAMI 320 65 61.6 SES Yes Single centre

Binary restenosis !! 12 12.3

Death, MI, stroke,

STRATEGY 175 26 62.6 SES Yes Single centre
or binary !! 3 24.2
restenosis

Cardiac death, MI,

TYPHOON 712 116 59.3 SES Yes 6 12.1
or TVR

BASKET-AMI 216 62.2 SES/PES Yes Single centre !!

Cardiac death,
MI, or TVR 6 18

Death,
Di Lorenzo et al 270 64 SES/PES Yes SingleMI,centre
or TVR !! 6 12
 100
100
Sirolimus-eluting
Sirolimus-eluting stent
stent
(%)
Survival (%)

95
95 92.5%
92.5%
Event-free Survival

90
90
Uncoated
Uncoated stent
stent
85
85

85.2%
85.2%
Event-free

80
80

75
75

70
70 P<0.001
P<0.001
00
00 30
30 60
60 90
90 120
120 180
180 210
210 270
270 300
300 330
330 360
360
Days
Days after
after Initial
Initial Procedure
Procedure
 Composite endpoint of death, reinfarction, or TLR at one
year (%)
15
p=0.12
Death, reinfarction,

12.6%
Less Angiographic
or TLR (%)

10 8.7% selection
No Angio follow-up
5

0
Paclitaxel-eluting stent Bare-metal stent
 Screened/Enrolled
Screened/Enrolled Ratio
Ratio
DES in STEMI in Multicenter studies

? ?
100

80
No angiographic bias
60
TYPHOON
No angiographic f-up 60 PASSION
40

20 35

0
 Trial Design
STEMI all-comer Patients
Aspirin + Clopidogrel + UFH
Before Arterial Sheath Insertion
1:1

Tirofiban*
Tirofiban* Abciximab
Abciximab
1:1 1:1

SES BMS SES BMS

Coronary
Clinical Angiography
FU only @ 1, 4, 8 ms,±1yr PCI
Stenting was the default strategy in pts
withand then
a RVD≥ 2.5yearly up to
mm at visual 5
estimation
*: given as a bolus of 25 g/kg, followed by an 18-24 hour infusion at 0.15 g/kg/min
 Primary Endpoint
8-month MACE
(CEC adjudicated)

2 0

Adjusted HR: 0.53 (97.5%CI: 0.33-0.83); p=0.006

1 5
U n co a ted sten t 1 4 .5 %

1 0

7 .8 %

5 S ir o lim u s - s t e n t
Prim ary End Point (%

P = 0 .0 0 3 9 a t L o g -r a n k te s t
0
0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 1 8 0 2 0 0 2 2 0 2 4 0 2 6 0

D a y s a f t e r R a n d o m iz a t io n
No. at Risk
Uncoated Stent 372 351 342 326 318
Sirolimus-Stent 372 355 351 347 343
Contrasting data from Registries
 RESEARCHregistry
RESEARCH registry--AMI
AMI
MACE free Survival
No. Stents
S u r v iv a l fr e e o f a d v e r s e e v e n t s ( % )

1.9
2
1.7
100
1

95
SES Months
(n=186) 90.6 of%clopidogrel
90
4 3.7
2.1
85 2

Bare stents 83.0 %

80 (n=183)

Use of GP IIb/IIIa %
75 HR 0.52
60 56%
95% CI 0.30 – 0.92; p=0.02
37%
0 60 120 180 240 300
30
Days Lemos et al. JACC 2004
Contrasting data from Registries
PREMIER
PREMIER Registry
Registry
500 DES-treated MI patients who were discharged on thienopyridine

Circulation. 2006;113:2803-2809
 Courtesy of PG Steg

Landmark post-discharge survival analysis – STEMI

All patients died in hospital were excluded, as well as the patients without follow-up
GRACE Registry - Baseline Characteristics
New York State's PCI Reporting System (PCIRS)

Hannan EL et al. JACC Intv 2008; 1:129

Mauri L. ACC 2008
Mr Registry!!
Why should we be concerned about DES in AMI?

May not be necessary

May not be cost-effective

Need to be proven safe

 Dominant
Dominant
€1,024.39
€1,024.39 average
average cost
cost saving
saving !!

1,000 bootstrap
replicates
1 2

Valgimigli et al. Int J Cardiol 2007

4 3
Why should we be concerned about DES in AMI?

May not be necessary

May not be cost-effective

Need to be proven safe

Why should we be concerned about ES in AMI?

Need to be proven safe

Prothrombotic milieu

Thrombus burden may affect drug uptake

and outcome

Premature discontinuation of antiplatelet

therapy
Meta-analysis of randomized trials on drug-eluting
stents vs. bare-metal stents in patients with AMI

Stent
Stent thrombosis
thrombosis

2.2%

1.69%

Kastrati et al. EHJ (2007) 28, 2706–2713

 MULTISTRATEGY: ARC Stent Thrombosis
(CEC adjudicated)

Uncoated Stent Sirolimus Stent

6% 6

P=0.45
P=0.31
4.5%4 , 5

P=0.65
3% 3

1.5%1, 5

0% 0

Definite/Probable
Definite Definite/Probable
Possible
- 1, 5
 Death/MI Landmark Analysis
50
The
The Benefit
Benefit is
is mainly
mainly carried
carried over
over

T ir o f ib a n + S E S
40 A b c ix im a b + B M S

30

H a z a r d R a t io 0 . 7 3 H a z a r d R a t io 1 . 1 6
[9 5 % C I: 0 .3 3 -1 .5 9 ]; p = 0 .4 0 [9 5 % C I: 0 .4 0 -3 .4 4 ]; p = 0 .7 8

20
17%

13%

?
10
9%
Probability of Death o

8%

0
0 200 400 600 800 1000 1200
D a y s a f t e r R a n d o m iz a t io n
Valgimigli et al Hotline ESC 2007
 Stent Thrombosis at 3 years
5 0

A b c ix im a b + B M S
T ir o f ib a n + S E S
4 0

3 0

2 0

p = 0 .7 6
(ARC classification)

1 0
6.8%
6.8%
Probability of Sten

5.7%
5.7%
0
0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 00 1 2 00

D a y s a f t e r R a n d o m iz a t io n
Valgimigli et al Hotline ESC 2007
 DES in AMI?
Who should we listen to………

Registry data?
All suggest the use
Randomized trials?
of DES in AMI
Metanalyses?