m. valgimigli university of ferrara italy multistrategy study design multistrategy study design
TRANSCRIPT
M. ValgimigliM. ValgimigliUniversity of FerraraUniversity of Ferrara
ItalyItaly
MultiStrategyStudy design
MultiStrategyStudy design
BackgroundBackground
Primary angioplasty is the current Primary angioplasty is the current preferred therapeutic option for patients preferred therapeutic option for patients with ST-segment elevation myocardial with ST-segment elevation myocardial infarction (STEMI).infarction (STEMI).
Routine coronary stent implantation in Routine coronary stent implantation in patients with STEMI decreases the need patients with STEMI decreases the need for target vessel revascularization (TVR).for target vessel revascularization (TVR).
Grines CL, et al. N Engl J Med 1999; 341: 1949Grines CL, et al. N Engl J Med 1999; 341: 1949Stone G, et al. Stone G, et al. N Engl J Med 2002; 346: 957N Engl J Med 2002; 346: 957
STEMI: STEMI: Stent and MortalityStent and Mortality
STEMI: STEMI: Stent and MortalityStent and Mortality
STEMI: STEMI: Stent and ReinterventionStent and Reintervention
STEMI: STEMI: Stent and ReinterventionStent and Reintervention
30 days30 days6 months6 months
What about external What about external validity?validity?
What about external What about external validity?validity?
In some of these trials In some of these trials randomization occurred after randomization occurred after angiography before PCI angiography before PCI In some of these studies In some of these studies randomization occurred after randomization occurred after balloon angioplastyballoon angioplastyIn none of these studies patients In none of these studies patients were recruited without prior were recruited without prior knowledge of coronary anatomyknowledge of coronary anatomy
Mostly excluded patients: Mostly excluded patients:
ShockShock
Diffusely diseased or small Diffusely diseased or small coronary coronary vesselvessel
Large thrombus burden Large thrombus burden
Severe coronary calcification or Severe coronary calcification or tortuosity tortuosity
Bifurcated lesionsBifurcated lesionsIdeal o
r good st
ent candid
ates
Ideal o
r good st
ent candid
ates
Participants:Participants: All Patients with STEMI randomly All Patients with STEMI randomly
assigned to stenting or balloon Angioplasty. assigned to stenting or balloon Angioplasty.
No exclusion criteria were appliedNo exclusion criteria were applied. .
Death or ReinfarctionDeath or Reinfarction
TV
R (
%)
TV
R (
%)
RR 0.98 (95%CI: 0.78-1.22)RR 0.98 (95%CI: 0.78-1.22)
N=1683N=1683
Heart 2005;91:641–645.
0
5
10
15
20
25
Stent
Balloon
LessonsLessons from the BMS from the BMS EraEra
BMS in the setting of STEMI is far BMS in the setting of STEMI is far from being the perfect solution for from being the perfect solution for restenosis and TVR may remain highrestenosis and TVR may remain high
New devices are needed which have New devices are needed which have to be tested in unselected (no to be tested in unselected (no angiographic selection bias) patient angiographic selection bias) patient populationpopulation
GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitorsThe word to the …The word to the …GuidelinesGuidelines
Primary PCI: Primary PCI: Class IIA indicationClass IIA indication
Class IIA indication with StentClass IIA indication with Stent
Class I indication without StentClass I indication without Stent
Class IIB for tirofiban and eptifibatideClass IIB for tirofiban and eptifibatide
Ab
cix
ima
Ab
cix
ima
bbAb
cix
ima
Ab
cix
ima
bb
STEMI UFH - ASAClopidogrel
Tirofiban SHDB
Abciximab stand. regimen
Cypher
BMS
CCU Cath-Lab
Valgimigli et al. Cardiovasc Drugs Ther 04; 18: 225-30
Study designStudy design
Inclusion Criteria: STEMI all comers: shock, elderly included
Exclusion Criteria: Contraindications to Gp IIb/IIIa
Inclusion Criteria: STEMI all comers: shock, elderly included
Exclusion Criteria: Contraindications to Gp IIb/IIIa
175 Randomized
SHDB Tirofiban(n=87)
Abciximab(n=88)
3 No PCI
1:1
219 Assessed for Eligibility 44 Excluded• 34 Not Meeting Inclusion Criteria
• 10 Refused to Participate
3 POBA 74 SES 7 BMS
84 PTCA
Clinical Follow-up
Angiographic Follow-up
Pts not eligible Refused to participate
4 POBA 77 BMS2 SES
83 PTCA 5 No PCI
3 3 74 7 4 77 2 5
0 1 62 4 1 64 1 0
3 2 6 0 3 4 0 50 0 6 3 0 9 1 0
Study ProfileStudy Profile
Valgimigli et al. JAMA 2005; 293: 2109-2117
85% 88%
77% 75%
30-Day Outcome30-Day Outcome n=175n=175
0
2
4
6
8
10
12
14
MACE Death Re-AMI TVR CVA
P=0.33
P>0.99 P=0.62 P=0.62
P=>0.99
%
Abciximab+BMS Tirofiban+SES
Valgimigli et al. JAMA 2005; 293: 2109-2117
Death/MI at 8 MonthsDeath/MI at 8 MonthsDeath/MI at 8 MonthsDeath/MI at 8 Months
0 50 100 150 200 250
Tim e after I n itial Procedure (days)
40
30
20
10
0
Pro
bability o
f Eve
nts
(%)
A bc + BMS (DEA TH / M I )SHDB Tir + SES (DEA TH / M I )
17%
13%
JAMA 2005; 293: 2109-2117
p=0.4
HR 0.71 [95% CI: 0.34-1.5]
0 50 100 150 200 250
Tim e after I n itial Procedure (days)
40
30
20
10
0
Pro
bability o
f Eve
nts
(%)
A bc + BMS (M A CE) SHDB Tir + SES (M A CE)
18%
32%
Death/MI/TVR at 8 MonthsDeath/MI/TVR at 8 Months
HR 0.53 [95% CI: 0.28-0.92]
p=0.043
JAMA 2005; 293: 2109-2117
8-Month Outcome8-Month Outcome n=175n=175
0
5
10
15
20
25
30
35
40
45
50
P=0.043
P=0.8 P=0.6
P=0.01
P>0.99
P=0.004
P=0.005
MACE Death MI TVR CVA 1° EndPointBR
%
Abciximab+BMS
Tirofiban+SES
50%
19%
Valgimigli et al. JAMA 2005; 293: 2109-117
STEMI All Comers PatientsSTEMI All Comers PatientsSTEMI All Comers PatientsSTEMI All Comers Patients
Aspirin + Clopidogrel Aspirin + Clopidogrel ++ UFHUFHIntent-to-stentIntent-to-stent
Aspirin + Clopidogrel Aspirin + Clopidogrel ++ UFHUFHIntent-to-stentIntent-to-stent
N ~ 730N ~ 730N ~ 730N ~ 730
TirofibanTirofibanTirofibanTirofiban AbciximabAbciximabAbciximabAbciximab
SESSESSESSES BMSBMSBMSBMS
MULTI-STRATEGYTrial Design
SESSESSESSES BMSBMSBMSBMS
Università degli Studi di Ferrara - Cattedra di Cardiologia
1:1
1:11:1
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
MULTI-STRATEGY
1.1. Whether Whether tirofiban administered at high bolus tirofiban administered at high bolus dose is non inferior to abciximab on the degree of dose is non inferior to abciximab on the degree of cumulative ST-segment resolution, expressed as cumulative ST-segment resolution, expressed as the proportion of patients reaching ≥ 50% the proportion of patients reaching ≥ 50% recovery, at 90’ after the mechanical recovery, at 90’ after the mechanical intervention.intervention.
2.2. Whether SES implantation –based on the Whether SES implantation –based on the intention-to-treat principle– is superior to BMS on intention-to-treat principle– is superior to BMS on the incidence of major adverse cardiovascular the incidence of major adverse cardiovascular events (MACE) within 8 months, defined as the events (MACE) within 8 months, defined as the composite of death, nonfatal myocardial composite of death, nonfatal myocardial infarction and clinically-driven target vessel infarction and clinically-driven target vessel revascularization (TVR). revascularization (TVR).
Primary objectivesPrimary objectives
Università degli Studi di Ferrara - Cattedra di Cardiologia
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
The effect of tirofiban infusion or SES implantation on The effect of tirofiban infusion or SES implantation on the MACE either singularly considered or as a the MACE either singularly considered or as a composite and on the incidence of stent thrombosis. composite and on the incidence of stent thrombosis.
The effect of tirofiban on the rate of TIMI 3 flow before The effect of tirofiban on the rate of TIMI 3 flow before and after intervention and on partial (and after intervention and on partial (≥≥50%) or 50%) or complete (complete (≥≥70%) cumulative ST segment resolution 70%) cumulative ST segment resolution or in the single lead with greatest ST changes.or in the single lead with greatest ST changes.
The effect of SES implantation on the rate of major The effect of SES implantation on the rate of major cardiovascular events either singularly considered or cardiovascular events either singularly considered or as a composite after thienopyridines discontinuationas a composite after thienopyridines discontinuation
TThe cost-effectiveness profile in STEMI of SES he cost-effectiveness profile in STEMI of SES implantation or tirofiban infusionimplantation or tirofiban infusion
The effect of tirofiban on the rate of bleeding and The effect of tirofiban on the rate of bleeding and thrombocytopeniathrombocytopenia
MULTI-STRATEGYMajor Secondary objectivesMajor Secondary objectives
MULTI-STRATEGY16 Participating centers
MULTI-STRATEGY16 Participating centers
Università degli Studi di Ferrara - Cattedra di Cardiologia
Ferrara, M.ValgimigliFerrara, M.Valgimigli
Valle Oppio, GF PercocoValle Oppio, GF Percoco
Arezzo. L. Bolognese Arezzo. L. Bolognese
Verona, M. Anselmi Verona, M. Anselmi
Bergamo, N. De CesareBergamo, N. De Cesare
Mirano, GP PasquettoMirano, GP Pasquetto
Pavia, E. BramucciPavia, E. Bramucci
Ancona, R. PivaAncona, R. Piva
Torino, I. SheibanTorino, I. Sheiban
Torino, S. ColangeloTorino, S. Colangelo
Roma, F. PratiRoma, F. Prati
Roma, R. VioliniRoma, R. Violini
ItalyItaly ArgentinaArgentina SpainSpain
Buenos Aires, A. RodriguezBuenos Aires, A. Rodriguez
Otamendi HospitalOtamendi HospitalMadrid, R. MorenoMadrid, R. Moreno
Huelva, José DíazHuelva, José Díaz
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.
STEMI All Comers PatientsSTEMI All Comers PatientsSTEMI All Comers PatientsSTEMI All Comers Patients
Aspirin + Clopidogrel Aspirin + Clopidogrel ++ UFHUFHIntent-to-stentIntent-to-stent
Aspirin + Clopidogrel Aspirin + Clopidogrel ++ UFHUFHIntent-to-stentIntent-to-stent
N ~ 730N ~ 730N ~ 730N ~ 730
TirofibanTirofibanTirofibanTirofiban AbciximabAbciximabAbciximabAbciximab
SESSESSESSES BMSBMSBMSBMS
MULTI-STRATEGYTrial Design
SESSESSESSES BMSBMSBMSBMS
Università degli Studi di Ferrara - Cattedra di Cardiologia
1:1
1:11:1ACC 2008
ACC 2008
Valgimigli M. et al Am Heart J. 2007 Jul;154(1):39-45.