MultiStrategy
Study design
M. Valgimigli
University of Ferrara
Italy
Background
Primary angioplasty is the current preferred
therapeutic option for patients with STsegment elevation myocardial infarction
(STEMI).
Routine coronary stent implantation in patients
with STEMI decreases the need for target
vessel revascularization (TVR).
Grines CL, et al. N Engl J Med 1999; 341: 1949
Stone G, et al. N Engl J Med 2002; 346: 957
STEMI:
Stent and Mortality
STEMI:
Stent and Reintervention
6 months
30 days
What about external validity?
Mostly excluded patients:
In some of these trials randomization
occurred after angiography before
Shock
PCI
Diffusely
or small coronary
In
some ofdiseased
these studies
randomization
occurred after balloon
vessel
angioplasty
Large thrombus burden
In none of these studies patients
Severe
coronary
calcification
were
recruited
without
prior or
knowledge
of coronary anatomy
tortuosity
Bifurcated lesions
N=1683
Heart 2005;91:641–645.
Participants: All Patients with STEMI randomly
assigned to stenting or balloon Angioplasty.
No exclusion criteria were applied.
25
RR 0.98 (95%CI: 0.78-1.22)
Death or Reinfarction
TVR (%)
20
15
10
5
0
Stent
Balloon
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
GP IIb/IIIa inhibitors
The word to the …Guidelines
Abciximab
Primary PCI:
Class IIA indication
Class IIA indication with Stent
Class I indication without Stent
Class IIB for tirofiban and eptifibatide
Study design
Inclusion Criteria: STEMI all comers: shock, elderly included
Exclusion Criteria: Contraindications to Gp IIb/IIIa
STEMI
Tirofiban SHDB
Cypher
Abciximab
stand. regimen
BMS
CCU
Cath-Lab
UFH - ASA
Clopidogrel
Valgimigli et al. Cardiovasc Drugs Ther 04; 18: 225-30
Study Profile
219 Assessed for Eligibility
44 Excluded
• 34 Not Meeting Inclusion Criteria
• 10 Refused to Participate
175 Randomized
1:1
SHDB Tirofiban
Abciximab
(n=87)
(n=88)
88%
85%
84 PTCA
3 No PCI
83 PTCA
3 POBA 74 SES 7 BMS
3
3
74
7
0
1
62
4
3
0
2
0
6
6
0
3
5 No PCI
4 POBA 77 BMS 2 SES
Clinical Follow-up
4
77
2
5
Angiographic Follow-up
1
64
1
0
Refused to participate
3
0
4
9
0
1
5
0
77%
Pts not eligible 75%
Valgimigli et al. JAMA 2005; 293: 2109-2117
30-Day Outcome
n=175
Abciximab+BMS
Tirofiban+SES
14
12
10
%
P=0.33
8
6
P>0.99 P=0.62
P=0.62
4
P=>0.99
2
0
MACE
Death
Valgimigli et al. JAMA 2005; 293: 2109-2117
Re-AMI
TVR
CVA
Death/MI at 8 Months
40
Abc + BMS (DEATH / MI)
SHDB Tir + SES (DEATH / MI)
30
(%)
20
17%
p=0.4
13%
10
Probability of Even
HR 0.71 [95% CI: 0.34-1.5]
0
0
JAMA 2005; 293: 2109-2117
50
100
150
Time after Initial Procedure
200
(days)
250
Death/MI/TVR at 8 Months
40
Abc + BMS (MACE)
SHDB Tir + SES (MACE)
32%
30
(%)
p=0.043
20
18%
10
Probability of Even
HR 0.53 [95% CI: 0.28-0.92]
0
0
JAMA 2005; 293: 2109-2117
50
100
150
Time after Initial Procedure
200
(days)
250
8-Month Outcome
n=175
P=0.005
50
45
40
35
% 30
25
20
15
10
5
0
50%
Abciximab+BMS
P=0.043
P=0.004
Tirofiban+SES
P=0.01
P=0.8
19%
P=0.6
P>0.99
MACE Death
MI
Valgimigli et al. JAMA 2005; 293: 2109-117
TVR
CVA
BR
1° EndPoint
MULTI-STRATEGY
Trial Design
STEMI All Comers Patients
Aspirin + Clopidogrel + UFH
Intent-to-stent
N ~ 730
1:1
SES
Tirofiban
Abciximab
1:1
1:1
BMS
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
SES
BMS
Università degli Studi di Ferrara - Cattedra di Cardiologia
MULTI-STRATEGY
Primary objectives


1. Whether tirofiban administered at high bolus dose is
non inferior to abciximab on the degree of cumulative
ST-segment resolution, expressed as the proportion of
patients reaching ≥ 50% recovery, at 90’ after the
mechanical intervention.
2. Whether SES implantation –based on the intention-totreat principle– is superior to BMS on the incidence of
major adverse cardiovascular events (MACE) within 8
months, defined as the composite of death, nonfatal
myocardial infarction and clinically-driven target vessel
revascularization (TVR).
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
Università degli Studi di Ferrara - Cattedra di Cardiologia
MULTI-STRATEGY
Major Secondary objectives





The effect of tirofiban infusion or SES implantation on
the MACE either singularly considered or as a composite
and on the incidence of stent thrombosis.
The effect of tirofiban on the rate of TIMI 3 flow before
and after intervention and on partial (≥50%) or
complete (≥70%) cumulative ST segment resolution or
in the single lead with greatest ST changes.
The effect of SES implantation on the rate of major
cardiovascular events either singularly considered or as a
composite after thienopyridines discontinuation
The cost-effectiveness profile in STEMI of SES
implantation or tirofiban infusion
The effect of tirofiban on the rate of bleeding and
thrombocytopenia
MULTI-STRATEGY
16 Participating centers
Italy
Argentina
Spain
Ferrara, M.Valgimigli
Buenos Aires, A. Rodriguez
Valle Oppio, GF Percoco Otamendi Hospital
Madrid, R. Moreno
Arezzo. L. Bolognese
Verona, M. Anselmi
Huelva, José Díaz
Bergamo, N. De Cesare
Mirano, GP Pasquetto
Pavia, E. Bramucci
Ancona, R. Piva
Torino, I. Sheiban
Torino, S. Colangelo
Roma, F. Prati
Roma, R. Violini
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
Università degli Studi di Ferrara - Cattedra di Cardiologia
MULTI-STRATEGY
Trial Design
STEMI All Comers Patients
Aspirin + Clopidogrel + UFH
Intent-to-stent
N ~ 730
1:1
SES
Tirofiban
Abciximab
1:1
1:1
BMS
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
SES
BMS
Università degli Studi di Ferrara - Cattedra di Cardiologia