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Preparazione Farmacologica alla PCI Primaria. Dalle Linee Guida ai Dati Degli Studi e dei Registri:...
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Transcript of Preparazione Farmacologica alla PCI Primaria. Dalle Linee Guida ai Dati Degli Studi e dei Registri:...
Preparazione Farmacologica alla PCI Primaria. Dalle Linee Guida ai Dati Degli Studi e dei Registri: sul Territorio
Leonardo De Luca, M.D., Ph.D., F.A.C.C.
Department of Cardiovascular SciencesInterventional Cardiology UnitEuropean HospitalRome, [email protected]
Conflict of interest: none
Convegno Area Emergenza-Urgenza ANMCO
Preparazione alla PTCA nelle Sindromi Coronariche Acute
Roma, 20 Marzo 2010
Symptoms onset and
identification
Call EMS ER Cath LabPre-hospital phase
Increasing Loss of Myocytes
Factors Associated with Delays in Factors Associated with Delays in Mechanical Reperfusion TxMechanical Reperfusion Tx
Symptoms onset and
identification
Call EMS ER Cath LabPre-hospital phase
Factors Associated with Delays in Factors Associated with Delays in Mechanical Reperfusion TxMechanical Reperfusion Tx
Increasing Loss of Myocytes
Symptoms onset and
identification
Call EMS ER Cath LabPre-hospital phase
Factors Associated with Delays in Factors Associated with Delays in Mechanical Reperfusion TxMechanical Reperfusion Tx
Increasing Loss of Myocytes
Practical Limitations of Primary PCI as a Universal Reperfusion Strategy
Time delays (DBT, transfer time, waiting time for next available ambulance etc.)
Availability of invasive facilities
Operators’ skillness and cath lab volume load
Reorganization of EMS systems not conductive to making PPCI
EMS lacking 12-lead ECG capabilities
Not all patients having STEMI are transported by EMS
Mandates to transport patients to the nearest facility
Transport in STEMI Transport in STEMI NetworksNetworks::a Continous Odissey a Continous Odissey
Is it my
ECG?
No, It Is
Your
Route
Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing
reperfusion therapy for AMI.
Terkeisen et al. J Electrocardiology 2005; 36: 187
Sym
pto
m o
nse
t to
bal
loo
n in
flat
ion
(m
inu
tes)
No prehospital diagnosisAdmission to local hospitalSubsequently transferredto interventional hospital
Prehospital diagnosisAdmission to local hospitalSubsequently transferredto interventional hospital
Prehospital diagnosisLocal hospital bypassed.Patients rerouted directlyto interventional hospital
PRAGUE-1
PRAGUE-2
MAASTRICT
DANAMI-2
Terkelsen et al.
Aashein et al.
Clinical Impact of Direct Referral to PCI Clinical Impact of Direct Referral to PCI Following pre-H Diagnosis of STEMIFollowing pre-H Diagnosis of STEMI
Is Possible to Apply These Findings in a Is Possible to Apply These Findings in a ““Real World”Real World” Setting? Setting?
0
50
100
66%
86.6%
PRE POST0
5
10
15
20
PRE POST
16%
9.5%
Implementation of Guidelines Improve the Standard of Care
The Vienna STEMI RegistryREPERFUSION THERAPY MORTALITY
Kalla K, et al. Circulation 2006;113:2398
%
EMS coordinated with 5 Heart Hospitals Rotated 24 hr PCI availability Evaluated frequency of PCI and Lytics Evaluated Mortality
The Ottawa Hospital Institute The Ottawa Hospital Institute STEMI Regional ProgramSTEMI Regional Program
95,979,7
44,9
11,9
0
50
100
150
DTB<90 min DTB<120 min
%
Le May RM et al. N Engl J Med 2008;358:231
Field transf
Inter-hosp. transf
Interhospitaltransfers
Fieldtransfers
P<0.001
Minutes
EC
G t
o B
allo
on
Tim
eP
rop
ort
ion
of
Pat
ien
ts (
%)
The Citywide Ottawa ProgramThe Citywide Ottawa ProgramTime to TreatmentTime to Treatment
p<0.001 p<0.001
0
10
20
30
40
50
60
70
80
90
37.5%
51%
85.7%
EMS12 LeadPre-Arrival Activation
No EMS12 Lead
EMS12 Lead
Prehosp Emerg Care 2006;10:374-377
Door to Balloon Time < 90 min
Establishing Infarct NetworksMedical Response Delay
Comparison of Existing Prehospital ECG Programs
Location Prehospital ECG Interpretation
Activate Catheterization Lab en Route to Hospital
Bypass Non-PCI Hospitals
BostonAm J Emerg Med. 2005;23:443
Paramedic interpretation Yes (activation by emergency department physician based on paramedic interpretation)
Yes (for all patients with “definite STEMI” or “possible STEMI”)
Los Angeles CountyAm Heart J. 2006;152:661
Computer algorithm interpretation
Yes (activation by emergency department physician based on computer algorithm interpretation)
Yes (for all patients with acute MI)
North CarolinaJAMA. 2007;298:2371
Mixed (used computer algorithm interpretation, paramedic interpretation, or wireless transmission)
Mixed (activation by paramedics or emergency department physician)
Mixed (paramedics occasionaly diverted patients with STEMI to nearest PCI hospital)
OttawaN Engl J Med. 2008;358:231
Paramedic interpretation Mixed (activation by paramedic through a central page operator)
Yes (for all patients with STEMI)
Time from Ambulance Arrival (min)
% T
reat
ed P
ts
5%
49%
97%
48%
In-H Thrombolysis
Pre-H Thrombolysis
0 20 40 60 80 100 120 140
Morrow DA, et al. J Am Coll Cardiol. 2002;40:71
# of Pts Treated Earlier with Prehospital Thrombolysis
Data from the ER-TIMI-19 Trial
(n=19) (n=18) (n=23)
(p=0.003, Group B vs. C+DNT)
% P
ts w
ith
An
gio
gra
ph
ic
Per
fusi
on
Sco
re
10
A B CPre-H Thrombolysis
Full DosePre-H Thrombolysis½ Dose + Urgent PCI
Primary PCI(not eligible to
lysis or excluded)
Smalling RW, et al. J Am Coll Cardiol. 2007;50:1612
Pre-hospital Thrombolysis Pre-hospital Thrombolysis as Facilitation to Primary PCIas Facilitation to Primary PCI
* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability
PCI CentreCath Lab
CommunityHospitalEmergencyDepartment
Cath / PCI within 6 Cath / PCI within 6 hrs regardless of hrs regardless of reperfusion statusreperfusion status
Cath and Cath and Rescue PCI Rescue PCI GP IIb/IIIa GP IIb/IIIa InhibitorInhibitor
TNK + ASA + Heparin / Enoxaparin + ClopidogrelTNK + ASA + Heparin / Enoxaparin + Clopidogrel
““PharmacoinvasivePharmacoinvasiveStrategy”Strategy”UrgentUrgent Transfer to PCI Transfer to PCI CentreCentre
Assess chest pain, STAssess chest pain, ST resolution resolution at 60-90 minutes after randomizationat 60-90 minutes after randomization
‘‘High Risk’ ST Elevation MI within 12 hours High Risk’ ST Elevation MI within 12 hours of symptom onset of symptom onset
Failed Reperfusion*Failed Reperfusion* Successful ReperfusionSuccessful Reperfusion
Elective Cath Elective Cath PCIPCI> 24 hrs later> 24 hrs later
““Standard Standard Treatment”Treatment”
Repatriation of stable patients within 24 hrs of PCI
The TRANSFER AMI Trial
Cantor WJ, et al. N Engl J Med 2009;360:2705
00
22
44
66
88
1010
1212
1414
1616
1818
00 55 1010 1515 2020 2525 3030
10.6
16.6
Days from Randomization
% of Patients% of Patients
n=496n=508
422468
415466
415463
414461
414460
412457
30-Day Death, re-MI, CHF, Severe 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia, Shock Recurrent Ischemia, Shock
OR=0.537 (0.368, 0.783); p=0.0013
Cantor WJ, et al. N Engl J Med 2009;360:2705
TIMI 3 Patency Before Primary PCI in TIMI 3 Patency Before Primary PCI in Randomized Trials on GP IIb/IIIa InhibitorsRandomized Trials on GP IIb/IIIa Inhibitors
TIMI 3 Flow (%)
Abciximab Tirofiban Integrilin Lysis
16
25
11
29
17
32 32
19
34
60
2
16
8 7 5
20
1015
10
0
10
20
30
40
50
60
70
Zorman
Reo-Mobile
ERAMI
ReoPro-bridging
ADMIRAL
Cutlip
TIGER-PA
On-TIME
INTAMI TNK
Early Late or no GP IIb/IIIa blocker use
27
14
TITAN
Acute myocardial infarctionAcute myocardial infarctiondiagnosed in ambulance or referral centerdiagnosed in ambulance or referral center
ASA + 600 mg Clopidogrel + UFHASA + 600 mg Clopidogrel + UFH
AngiogramAngiogram
Tirofiban *Tirofiban *PlaceboPlacebo
Transportation
PCI centerAngiogramAngiogram
TirofibanTirofibanprovisionalprovisional
Tirofiban Tirofiban cont’dcont’d
N=9846/2006-11/2007
PCI
*Bolus: 25 µg/kg & 0.15 µg/kg/min infusion
Ongoing Tirofiban In Myocardial Infarction Ongoing Tirofiban In Myocardial Infarction Evaluation: ON-TIME 2 TrialEvaluation: ON-TIME 2 Trial
Van’t Hof AW, et al. Lancet. 2008;372:537
Cumulative ST- Deviation over Time
0
4
8
12
16
Diagnosis pre Angio 60min 90 min
Placebo Tirofiban 14.3±9.1
12.1±9.4
5.9±8.1
4.8±6.3
14.5±9.1
10.9±9.2
4.4±5.3
3.3±4.3
0.0020.0220.028p=0.84
[mm]
Ongoing Tirofiban In Myocardial Infarction Ongoing Tirofiban In Myocardial Infarction Evaluation: ON-TIME 2 TrialEvaluation: ON-TIME 2 Trial
Van’t Hof AW, et al. Lancet. 2008;372:537
Ongoing Tirofiban In Myocardial Infarction Ongoing Tirofiban In Myocardial Infarction Evaluation: ON-TIME 2 TrialEvaluation: ON-TIME 2 Trial
Residual ST-Deviation and Mortality
%
Van’t Hof AW, et al. Lancet. 2008;372:537
Dudek D, et al. Am Heart J 2008;156:1147
The EUROTRANSFER Registry:Impact of Prehospital Abciximab on TIMI flow
Before PCI After PCI
p<0.0001 p<0.001
Mehran R, et al. Lancet 2009;374:1149
Bivalirudin in Primary PCI. Bivalirudin in Primary PCI. 1-Year Results of the HORIZONS-AMI1-Year Results of the HORIZONS-AMI
18.3%
15.6%
HR 0.83 (95% CI 0.71-0.97)p=0.022
0
5
10
20
0 6 12
Bivalirudin (n=1800)
Control (n=1802)
HR 0.61 (95% CI 0.48-0.78)p=0.0001
9.2%
5.8%
0
4
8
12
0 6 12
HR 1.00 (95% CI 0.82-1.21)p=0.98
11.9%11.9%
0
5
10
15
15
0 6 12
Time (months) Time (months)
Time (months)
Feasibility and Safety of Prehospital Feasibility and Safety of Prehospital Administration of BivalirudinAdministration of Bivalirudin During STEMIDuring STEMI
Sejersten, M, et al. Am J Cardiol 2009;103:1635
%
**
* *
*: p<0.05
Clopidogrel LD in Pts Undergoing Primary PCI Clopidogrel LD in Pts Undergoing Primary PCI Results from the HORIZONS-AMIResults from the HORIZONS-AMI
Dangas G, et al. J Am Coll Cardiol 2009;54:1438
300 mg Loading Dose
600 mg Loading Dose
p=0,07
p=0,02
p=0,004
p=0,0007
p=0,0497 p=0,004Bivalirudin
Unfractioned Heparinplus GlycoproteinIIb/IIIa Inhibitors
Clopidogrel: Double vs SD.Clopidogrel: Double vs SD.STEMI PCI CohortSTEMI PCI Cohort
S. Mehta @ TCT 2009; September 24; San Francisco, CA
Outcome Standard clopidogrel
(n=3175)
Double-dose clopidogrel
(n=3171)
Hazard ratio (95% CI)
Definite stent thrombosis
1.8 1.0 0.54 (0.35–0.84)
All stent thrombosis
3.5 2.5 0.72 (0.54–0.96)
MI 1.9 1.2 0.63 (0.41–0.94)
MI or stent thrombosis
4.0 2.8 0.70 (0.54–0.92)
CURRENT major 1.2 1.4 1.16 (0.75–1.78)
CURRENT severe 0.9 1.1 1.18 (0.72–1.93)
Clopidogrel Administered Pre-h to Improve Clopidogrel Administered Pre-h to Improve Primary PCI: the CPrimary PCI: the CIPAMI StudyIPAMI Study
Pre-hospital Hospital until discharge or day 7
Prim
ary
angi
ogra
phy
Prim
ary
endp
oint
PC
I
(Sec
onda
ry e
ndpo
ints
)D
eath
, Re-
MI,
TV
R
RAspirin +
UFH/enoxaparin
n = 327Clopidogrel 600 mg
n = 327No loading
Treatment according to investigator
Clopidogrel loading prior to PCI strongly recommended
n = 654with STEMI
Acute STEMI <6hAngina >20 minST elevation >2
leadsor
new/presumed LBBB
Zeymer U et al. Cardiology 2007;108:265
Pre-hospitalP
CI
(Pri
mar
y en
dp
oin
ts)
TM
PG
R
Clopidogrel 600 mgn = 150
with STEMIAcute STEMI <12h
Angina >30 minST elevation >0.2
mV in >2 leadsor
new/presumed LBBB
P.I.s: Leonardo Bolognese and Kenneth DucciOspedale S. Donato, Arezzo
Three Different LD of Clopidogrel Administered Three Different LD of Clopidogrel Administered at FMC in AMI. The LOAD & GO Trialat FMC in AMI. The LOAD & GO Trial
Clopidogrel 900 mg
None
Clopidogrel
300 mg
Aspirin +UFH/enoxaparin
Prasugrel in Primary PCI.Prasugrel in Primary PCI.Data from Data from TRITON-TIMI 38TRITON-TIMI 38
Montalescot G, et al. Lancet 2009;373:723
p=0.0084p=0.0232 p=0.3359 p=0.6451
p=0.0017 p=0.0221p=0.0205 p=0.0250
Prasugrel
Clopidogrel
Days after Randomization Days after Randomization
0
5
10
15
0
5
10
15
CV death/non-fatal MI/non-fatal stroke CV death/non-fatal MI/urgent TVR
Stent Thrombosis TIMI major bleeding (no CABG)
0 200 450
0 200 450 0 200 450
0 200 450
PLATO Randomized Trial.PLATO Randomized Trial.STEMI CohortSTEMI Cohort
@ AHA 2009; November 14-18 2009; Orlando, FL
End point Ticagrelor
(180 mg+90 mg BID)
Clopidogrel
(300 mg+75 mg daily)
Hazard ratio for ticagrelor
p
Primary end point: death from vascular causes, MI, or stroke
9.3 11.0 0.85 0.02
All-cause mortality 4.9 6.0 0.82 0.04
CV mortality 4.5 5.4 0.84 0.09
Definite stent thrombosis
1.6 2.5 0.61 0.01
MI 4.7 6.1 0.77 0.01
Primary safety event: major bleeding
9.0 9.3 0.96 0.63
The need to shorten delays and to improve the quality of care for STEMI pts is urgent. We cannot wait! It’s up to us!!
Prehospital management is a key issue in 2010!
Emulating successful organizations can speed effective improvement.
A combined strategy of immediate thrombolysis or potent antithrombotic agents in the ambulance followed by PCI could theoretically provide early, complete and successful myocardial reperfusion.
The Tension Between Needing to Improve Care and Knowing How to Do it!