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Dott. Antonio ButeraLamezia Terme
Roma, 20 marzo 2010
Lamezia Terme U. O. CARDIOLOGIA con UTIC
Preparazione farmacologica alla PTCA: STEMI Negli ospedali senza emodinamica
12
2009
Facilitaded and Rescue PCI…non longer used…potentially misleading labels
Scopi del trattamento farmacologico pre PTCA Limitazione di eventi e
riduzione del danno ischemico pre-PCI
“Facilitazione” dell’angioplastica
Riduzione delle complicanze peri e post-procedurali (trombosi dello stent, ischemia)
(Il tutto con minori effetti pro-emorragici) -I sanguinamenti maggiori moltiplicano MACE: “GRACE” EHJ 2003; Eikelboom JW et al: Circulation 2006; Nikolski E et al: EHJ 2007; “CRUSADE “ Circulation 2009-
Facilitata
Razionale dell’Angioplastica facilitata La maggiore pervietà dell’IRA prima
dell’angioplastica migliora l’outcome
Su
rviv
al (
%)
Months
6 monthsmortality
log-rank p for trend= 0.009
100%
98%
96%
94%
92%
90%
0 1 2 3 4 5 6
0.5%
2.8%
4.4%
Stone GW Circulation 2001;104:636
TIMI 3 (n=375)
TIMI 2 (n=295)
TIMI 0/1 (n=1,657)
ASSENT- 4 PCI: study design
ASA + UFH (bolus 40U/kg)
+ TNK-tPA
Primary endpoints: death, heart failure or cardiogenic shock at 90 days
n = 2000 n = 2000
Immediate PTCA
Stent or clopidogrelat researcher’s
discretionNo anti-GP IIb/IIIa
ASA + UFH (bolus 70u/Kg)
Immediate PTCA
Stent, clopidogrel oranti-GP IIb/IIIaat researcher’s
discretion
IMA ST(< 6h)
Lancet 2006
ASSENT- 4 PCI Trial: TIMI Flow GradeASSENT- 4 PCI Trial: TIMI Flow Grade
43,6%
95,3%
15,0%
97,6%
0%
20%
40%
60%
80%
100%
TFG 3 prior to PCI TFG 2/3 post-PCI
TNK + PCI PCI alone
43,6%
95,3%
15,0%
97,6%
0%
20%
40%
60%
80%
100%
TFG 3 prior to PCI TFG 2/3 post-PCI
TNK + PCI PCI alone
TIMI grade 3 flow prior to PCI and TIMI TIMI grade 3 flow prior to PCI and TIMI grade 2/3 flow post-PCI (%)grade 2/3 flow post-PCI (%)
p<0.001p<0.001
•TIMI grade 3 flow prior to TIMI grade 3 flow prior to PCI was present more PCI was present more frequently in the TNK + PCI frequently in the TNK + PCI arm (43.6% vs 15.0%)arm (43.6% vs 15.0%)
•TIMI grade 2/3 post-PCI TIMI grade 2/3 post-PCI was slightly higher in the was slightly higher in the PCI alone group (95.3% vs PCI alone group (95.3% vs 97.6%)97.6%)
p=0.03p=0.03
Lancet 2006
ASSENT-4: Primary EndpointASSENT-4: Primary Endpointmortality, CHF, Shock at 90 daysmortality, CHF, Shock at 90 days
Primary Composite Endpoint at Day 90
13,0%
19,0%
0,0%
5,0%
10,0%
15,0%
20,0%
Perc
enta
ge
Primary PCI (n=829) TNK Facililated PCI (n=833)
p=0.04
Lancet 2006
ASSENT-4 PCI : in-hospital cardiac events
Event TNK+PCI (%) PCI alone (%) p
Re-MI 4.1 1.9 0.01
Abrupt vessel closure 1.9 0.1 <0.001
Repeat TVR 4.4 1.0 <0.001
Pericarditis 0.7 0.1 0.07
Tamponade 0.6 0.4 0.50
Cardiac rupture 0.9 0.2 0.11
EM dissociation 1.7 1.0 0.20
Pulmonary edema 3.4 3.1 0.78
Ventricular fibrillation 5.6 3.7 0.08
Lancet 2006
ASSENT-4 PCI: in-hospital stroke rates
van de Werf F. European Society of Cardiology Congress 2005; September 4-7, 2005; Stockholm, Sweden.
Outcome TNK+PCI (%) PCI alone (%) p
Total stroke 1.81 0 <0.001
Intracranial hemorrhage 0.97 0 0.004
Ischemic stroke 0.60 0 0.03
Hemorrhagic conversion 0.12 0 0.50
Unclassified 0.24 0 0.25
Lancet 2006
Conclusioni ASSENT - 4
Primary PCI with in lab Abciximab
Major ObjectivesMajor Objectives
R
Reteplase/Abciximab Facilitated
Primary PCI
?Abciximab Facilitated
Primary PCI
To test if Reteplase/Abciximab is superior to facilitation with Abciximab aloneTo test if Reteplase/Abciximab is superior to facilitation with Abciximab aloneTo test if Abciximab facilitation is superior to Primary PCI with in lab AbciximabTo test if Abciximab facilitation is superior to Primary PCI with in lab Abciximab
2°:
?
?
1°1° - To test if Reteplase/Abciximab Facilitated PCI is superior to Primary PCI - To test if Reteplase/Abciximab Facilitated PCI is superior to Primary PCI with in lab Abciximabwith in lab Abciximab
Primary end-point:mortality, CHF, VF, Shock at 90 daysPrimary end-point:mortality, CHF, VF, Shock at 90 days
NEJM 2008
TIMI Flow in IRA Pre-PCI TIMI Flow in IRA Pre-PCI % Subjects with TIMI 2/3 (Patency) % Subjects with TIMI 2/3 (Patency)
Pre-PCIPre-PCI
0
20
40
60
80
100
12 %12 %
13 %13 %
11 %11 %
15 %15 %
25 %25 %
36 %36 %
25 %25 % 26 %26 %
61 %61 %
Primary PCI (in Primary PCI (in lab Abciximab) lab Abciximab)
(n=790)(n=790)
Abciximab Abciximab Facilitated PCI Facilitated PCI
(n=809)(n=809)
Reteplase/Abciximab Reteplase/Abciximab Facilitated PCI Facilitated PCI
(n=815)(n=815)
Per
cen
tag
eP
erce
nta
ge
TIMI 2TIMI 2
TIMI 3TIMI 3
p < 0.0001p < 0.0001
p < 0.0001p < 0.0001
Primary Endpoint:Primary Endpoint:mortality, CHF, VF, Shock at 90 daysmortality, CHF, VF, Shock at 90 days
Primary Composite Endpoint at Day 90
10,7% 10,5% 9,8%
0,0%
5,0%
10,0%
15,0%
20,0%
Perc
enta
ge
Primary PCI with in lab Abciximab (n=806)
Abciximab Facililated PCI (n=818)
Reteplase/Abciximab Facilitated PCI (n=828)
p=0.55
TIMI Major or Minor BleedingTIMI Major or Minor Bleeding (nonintracranial) through Discharge/Day7 (nonintracranial) through Discharge/Day7
TIMI Bleeding through Discharge/Day 7
2,6%4,3%
6,9%
4,1%6,0%
10,1%
4,8%
9,7%
14,5%
0%
5%
10%
15%
20%
25%
30%
TIMI Major TIMI Minor TIMI Major or Minor
Per
centa
ge
Primary PCI with In Lab Abciximab (n=795)
Abciximab Facililated PCI (n=805)
Abciximab/Reteplase Facilitated PCI (n=814)
p=0.025
p=0.025
p<0.001
p=0.127
p=0.008
p=0.141
p<0.001
p=0.006p=0.547
…il rapporto rischio/beneficio della pPCI con Abciximab somministrato direttamente in emodinamica è migliore delle due strategie di facilitazione…
CONCLUSIONI
(19 studi)
Ma se la pPCI non si potesse proprio fare….specialmente nei pazienti ad alto rischio…
Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days
CARESS Study designCARESS Study designSTEMI patients <12 hrs from symptom onsetAdmitted to centres without PCI facilities and
at least one high risk featurehigh risk feature: >15 mm ST Elevation new onset LBBB, previous MI, Killip Class >2, < 35% LVEF
Urgent transfer afterlysis to nearest PCI centre
for PCI plus stenting
Admit to CCU and only transfer for PCI if persistent
ST elevation at 90 min (>50% basal ECG), chest pain or haemodynamic
compromise
ASA 300-500 mg iv;ASA 300-500 mg iv; Reteplase half dose; UFH (40 U/kg -max 3000-; 7 U/kg/h); Abciximab 0.25 mg/kg bolus 0.125 g/kg/min x 12 h
ASA 300-500 mg iv;ASA 300-500 mg iv; Reteplase half dose; UFH (40 U/kg -max 3000-; 7 U/kg/h); Abciximab 0.25 mg/kg bolus 0.125 g/kg/min x 12 h
Lancet 2008
Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days
Il beneficio del trasferimento immediato si è ottenuto malgrado 1/3 dei pazienti del braccio di controllo sia stato trattato con la Rescue. Il rischio di sanguinamento non è stato differente nei dueGruppi (e comunque basso: solo 5 ICH nei 598 pz )
PCI CentrePCI CentreCath LabCath Lab
CommunityCommunityHospitalHospitalEmergencyEmergencyDepartmentDepartment
Cath / PCI within 6 Cath / PCI within 6 hrs regardless of hrs regardless of
reperfusion statusreperfusion status
Cath and Rescue Cath and Rescue PCI PCI GP IIb/IIIa GP IIb/IIIa
InhibitorInhibitor
TNK + ASA + Heparin / Enoxaparin + ClopidogrelTNK + ASA + Heparin / Enoxaparin + Clopidogrel
““PharmacoinvasivePharmacoinvasiveStrategy”Strategy”
UrgentUrgent Transfer to PCI Centre Transfer to PCI CentreAssess chest pain, STAssess chest pain, ST resolution resolution
at 60-90 minutes after randomizationat 60-90 minutes after randomization
‘‘High Risk’High Risk’ ST Elevation MI within 12 hours of ST Elevation MI within 12 hours of symptom onsetsymptom onset
Failed ReperfusionFailed Reperfusion** Successful ReperfusionSuccessful Reperfusion
Elective Cath Elective Cath PCIPCI
> 24 hrs later> 24 hrs later
““Standard Treatment”Standard Treatment”
* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability
Repatriation of stable patients within 24 hrs of PCI
Randomization stratified by age (Randomization stratified by age (≤75 vs. > 75) and by enrolling site≤75 vs. > 75) and by enrolling siteNEJM 2009
Primary end-point: 30-day composite Death, Reinfarction, recurrent ischemia, CHF, Shock
Conclusioni
In paz con STEMI ad alto rischio sottoposti alla fibrinolisi in centri periferici, il trasferimento entro 6 ore al centro hub per eseguire la PCI si associa ad una riduzione significativa di eventi ischemici, (malgrado il ricorso in circa il 40% dei pazienti alla PCI rescue)
senza incrementare gli eventi emorragici, La PCI precoce dopo trombolisi, si è dimostrata
più “safe” che nei precedenti trials (progressi con gli stent ed altra terapia concomitante –Clopidogrel-?)
1.Se possibile pPCI
2.Se non possibile pPCI
2009
Anti IIB/IIIA pre-cathlab Molti studi eseguiti prima della doppia
antiaggregazione non più attuali. BRAVE-3 (Abciximab): clinicamente neutro;
ON-TIME 2 (Tirofiban): clinicamente neutro. MULTISTRATEGY: Abciximab vs Tirofiban e
BMS vs DES (Sirolimus) – vantaggio del DES. FINESSE: Braccio abciximab clinicamente
neutro (con + emorragie rispetto alla somministrazione in emodinamica)
2009
Am Heart J 2008
Come identificare, eventualmente, i pazienti della Classe 2B?
0
2
4
6
8
10
12
14
16
<65 aa >/ =65 aa
EALA
0
2
4
6
8
10
12
14
16
18
<65 aa >/ =65 aa
EALA
Early abciximab administration before primary percutaneous coronary intervention improves clinical outcome in elderly patients transferred with ST-elevation myocardial infarction: Data from the EUROTRANSFER registry
Dziewiers et al: Int J Cardiol 2009
30-day death 30-day death + Reinfarction% %
P = 0.001
Nessuna differenza per emorragie nel gruppo >/= 65 aa
P = 0.001
2009
ISIS-2ISIS-2 (Second International Study of Infarct Survival) Collaborative Group, Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarctions:
ISIS-2. Lancet 1988 ii 349-360
-20%
Collaborative meta analysis of randomised trials ofantiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71-86
NNT = 26
ACC/AHA Guidelines 2004 (invariate per l’ASA)
ESC Guidelines 2008
Schomig A. N Engl J Med 2009
Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and Ticagrelor
Il beneficio del Clopidogrel (300>75) è maggiore nei pazienti sottoposti a PCI
Medical Rx GroupMedical Rx Group
PlaceboPlacebo
ClopidogrelClopidogrelRR: 0.80 (0.69-0.92)RR: 0.80 (0.69-0.92)
0.200.20
44
0.150.15
0.100.10
0.050.05
0.00.0100100 200200 300300
CV
D/M
I/Str
oke
ClopidogrelClopidogrel
0.200.20
44
0.150.15
0.100.10
0.050.05
0.00.0100100 200200 300300
PCI GroupPCI Group
PlaceboPlacebo
RR: 0.72 (0.57-0.90)RR: 0.72 (0.57-0.90)CV
D/M
I/Str
oke
CURE Primary end-point: CVD+MI+Stroke)
-19% -30%
NEJM 2001
PCI-
The CURE Investigators: Lancet 2001
NEJM 2005
Clarity TIMI 28 (Fibrinolisi)
-36%
JAMA 2005
PCI- Clarity TIMI 28
-46%
Clopidogrel No
Trial Pretreatment Pretreatment
PCI-CURE 3.6 5.1
CREDO n/a n/a
PCI-CLARITY 4.0 6.1
Overall 3.7 5.5
Clopidogrel NoTrial Pretreatment Pretreatment
PCI-CURE 2.9 4.4
CREDO 6.0 7.1
PCI-CLARITY 3.3 5.4
Overall 3.9 5.5
Meta-Analysis of Clopidogrel PretreatmentMeta-Analysis of Clopidogrel Pretreatment
1.00.25 2.00.5
1.00.25 2.00.5OR (95% CI)
OR (95% CI)
OR 0.67OR 0.67P=0.005P=0.005OR 0.67OR 0.67P=0.005P=0.005
FavorsPretreatment
FavorsNo Pretreatment
OR 0.71OR 0.71P=0.004P=0.004OR 0.71OR 0.71P=0.004P=0.004
Sabatine MS et al. JAMA 2005
MI before PCI (%)
CVD or MI after PCI (%)
CURRENT OASIS: Study Design, Flow and Compliance
25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%)Planned Early (<24 h) Invasive Management with intended PCIIschemic ECG Δ (80.8%) or ↑cardiac biomarker (42%)
25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%)Planned Early (<24 h) Invasive Management with intended PCIIschemic ECG Δ (80.8%) or ↑cardiac biomarker (42%)
PCI 17,232(70%)
Angio 24,769(99%)
Angio 24,769(99%)
No PCI 7,855 (30%)
No Sig. CAD 3,616 CABG 1,809 CAD 2,430
Randomized to receive (2 X 2 factorial):
CLOPIDOGREL: Double-dose (600 mg then150 mg/d x 7d then 75 mg/d) vs Standard dose (300 mg then 75 mg/d)
ASA: High Dose (300-325 mg/d) vs Low dose (75-100 mg/d)
Efficacy Outcomes: CV Death, MI or stroke at day 30 Stent Thrombosis at day 30
Safety Outcomes: Bleeding (CURRENT defined Major/Severe and TIMI Major)Key Subgroup: PCI v No PCI
Efficacy Outcomes: CV Death, MI or stroke at day 30 Stent Thrombosis at day 30
Safety Outcomes: Bleeding (CURRENT defined Major/Severe and TIMI Major)Key Subgroup: PCI v No PCI
Complete Followup 99.8%
Complete Followup 99.8%
Cu
mu
lati
ve H
azar
d
0.0
0.01
0.02
0.03
0.04
0 3 6 9 12 15 18 21 24 27 30
Clopidogrel Standard
Clopidogrel Double
HR 0.8595% CI 0.74-0.99
P=0.036
15% RRR15% RRR
CURRENT OASIS: Double vs Standard Dose Primary Outcome (CV Death, MI or Stroke): PCI
Patients
DaysESC 2009
Days
Cu
mu
lati
ve H
azar
d0.
00.
004
0.00
80.
012
0 3 6 9 12 15 18 21 24 27 30
Clopidogrel Standard Dose
Clopidogrel Double Dose
42% RRR
HR 0.5895% CI 0.42-0.79
P=0.001
CURRENT OASIS 7: Double vs Standard DoseDefinite Stent Thrombosis (Angio confirmed)
ESC 2009
0.50 1.50
Overall
NSTEMI/UA STEMI
MaleFemale
Age <= 65 yrsAge > 65 yrs
Non-DiabeticPrev Diabetic
No Inhosp GPIIb/IIIaGPIIb in hosp
No Prot Pump InhibProt Pump Inhib
Non-smokerCurrent Smoker
ASA LowASA High
17232
10886 6346
13009 4223
10975 6257
13400 3831
12288 4936
7675 5557
10845 6380
8620 8612
4.5
4.2
5.0
4.1
5.8
3.0
7.1
4.2
5.6
3.9
6.0
3.8
5.7
4.9
3.8
4.2
4.8
3.9
3.6
4.2
3.6
4.6
2.7
6.0
3.6
4.9
3.5
4.7
3.2
4.2
4.6
2.6
4.3
3.5
0.805
0.419
0.702
0.836
0.465
0.408
0.045
0.024
0.50 1.50
3.7
3.6
4.0
3.5
4.6
2.9
5.2
3.6
4.1
3.1
5.2
3.1
4.8
3.9
3.4
3.6
3.8
3.0
3.1
2.8
3.0
3.0
2.2
4.4
2.8
3.6
2.5
4.1
2.3
3.3
3.5
2.1
3.2
2.7
0.248
0.148
0.418
0.567
0.894
0.613
0.050
0.191
CV Death, MI or StrokeCV Death, MI or Stroke MI or Stent ThrombosisMI or Stent Thrombosis
Clopidogrel: Double v Standard DosePCI Cohort Subgroups
Std %Std % Double %Double % Std %Std % Double %Double %Intxn PIntxn P Intxn PIntxn P
Double Dose Better
Double Dose Better
Double Dose Better
Double Dose Better
2N2N
Clopidogrel Double vs Standard DoseBleeding Overall Population
Clopidogrel Standar
dN=12579
DoubleN=12508
HazardRatio
95% CI P
TIMI Major 0.95 1.04 1.09 0.85-1.40 0.50
CURRENT Major 2.0 2.5 1.25 1.05-1.47 0.01
CURRENT Severe 1.5 1.9 1.23 1.02-1.49 0.03
Fatal 0.11 0.13 1.15 0.56-2.35 0.71
ICH 0.05 0.03 0.67 0.19-2.37 0.53
RBC transfusion ≥ 2U
1.76 2.21 1.26 1.06-1.51 0.01
CABG-related Major 0.9 1.0 1.10 0.85-1.42 0.48
TRITON TIMI 38: Study Design
Double-blind
ACS: STEMI (35%) or UA/NSTEMI) & Planned PCI
ASA
PRASUGREL60 mg LD/ 10 mg MD
CLOPIDOGREL300 mg LD/ 75 mg MD
1o endpoint: CV death, MI, Stroke2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch
CV death, MI, UTVR Stent Thrombosis (ARC definite/prob.) Safety endpoints: TIMI major bleeds, Life-threatening bleedsKey Substudies: Pharmacokinetic, Genomic
Median duration of therapy - 12 months
N= 13,608
NEJM: 2009NEJM 2007
0
5
10
15
0 30 60 90 180 270 360 450
HR 0.81(0.73-0.90)P=0.0004
Prasugrel
Clopidogrel
HR 0.80P=0.0003
HR 0.77P=0.0001
Days
Pri
ma
ry E
nd
po
int
(%)
12.1(781)
9.9 (643)
TRITON TIMI 38 Primary Endpoint: CV Death, MI, Stroke
NNT= 46
Days
NEJM: 2009NEJM 2007
TRITON TIMI 38: Stent Thrombosis (Definite + Probable)
0
1
2
3
0 30 60 90 180 270 360 450
HR 0.48P <0.0001
Prasugrel
Clopidogrel2.4
(142)
NNT= 77
1.1 (68)
Days
En
dp
oin
t (%
)
Any Stent at Index PCI N= 12,844
NEJM 2007
B
OVERALL
No GPIGPI
DESBMS
DMNo DM
>7565-74
<65
FemaleMale
STEMIUA/NSTEMI
0.5 1 2Prasugrel Better Clopidogrel BetterHR
Age
Reduction in risk (%)18
2112
25146
1430
2018
2116
19
21
Pinter = NS
TRITON TIMI 38: CV Death, MI, StrokeMajor Subgroups
CrCl > 60CrCl < 60 14
20
NEJM 2007
TRITON TIMI 38 (STEMI: 3534 pt)CVD + nf MI + nf Stroke CVD +nf MI + Urg target v revas.
Stent thrombosis TIMI Major bleeding
Lancet 2009
1,8
0,9 0,9
0,10,3
2,4
1,41,1
0,4 0,3
0
2
4
TIMI MajorBleeds
LifeThreatening
Nonfatal Fatal ICH
TRITON TIMI 38: Bleeding Events%
Eve
nts
P=0.03
ClopidogrelClopidogrel
PrasugrelPrasugrel
P=0.01 P=0.23 P=0.74P=0.002
ICH in Pts w Prior Stroke/TIA
(N=518)
Clop 0 (0) % Pras 6 (2.3)% (P=0.02)
NEJM: 2007NEJM 2007
PLATO study design
Primary endpoint: CV death + MI + Stroke Primary safety endpint: Total major bleeding
6–12-month exposure
ClopidogrelIf pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,
then 75 mg qd maintenance;(additional 300 mg allowed pre PCI)
Ticagrelor180 mg loading dose, then
90 mg bid maintenance;(additional 90 mg pre-PCI)
NSTE-ACS (mod-to-high risk) STEMI 37% (if primary PCI)Clopidogrel-treated or -naive;
randomised within 24 hours of index event (N=18,624)
NEJM: 2009NEJM: 2009
Wallentin L et al. N Engl J Med 2009;10.1056
PLATO: Risultati end-point primario (CVD+MI+Stroke)
8,688
8,763
0 10 20 30
8
6
4
2
0
Cu
mu
lati
ve i
nci
de
nce
(%
)
Clopidogrel
Ticagrelor
4.77
5.43
HR 0.88 (95% CI 0.77–1.00), p=0.045
No. at risk
Clopidogrel
Ticagrelor
9,291
9,333
8,875
8,942
8,763
8,827
Days after randomisation
31 90 150 210 270 330
8
6
4
2
0
Clopidogrel
Ticagrelor
5.28
6.60
8,688
8,673
8,286
8,397
6,379
6,480
Days after randomisation*
HR 0.80 (95% CI 0.70–0.91), p<0.001
8,437
8,543
6,945
7,028
4,751
4,822
Cu
mu
lati
ve i
nci
de
nce
(%
)
*Excludes patients with any primary event during the first 30 days
NEJM: 2009
Clopidogrel
Ticagrelor
9,186
9,235
7,305
7,246
6,930
6,826
6,670 5,209
5,129
3,841
3,783
3,479
3,433
0 60 120 180 240 300 360
10
5
0
15
Clopidogrel
Ticagrelor
11.2011.58
6,545
HR 1.04 (95% CI 0.95–1.13), p=0.434
K-M
est
imat
ed r
ate
(% p
er y
ear)
PLATO: Time to major bleeding – primary safety event
NEJM: 2009
PLATO-STEMI18,758 patients
enrolled in PLATO
134 patients not randomized
18,624 patients randomized
NSTEMI/UA/other: 10,194 patients
STEMI: 8,430 patients
Randomized to ticagrelor: efficacy
population N= 4,201
Randomized to clopidogrel: efficacy population N= 4,229
No intake of study medication: 36
patients
No intake of study medication: 48
patients
Safety population N=4,165
Safety population N=4,181
PLATO-STEMI Primary endpoint: CV death, MI or stroke
0 1 2 3 4 5 6 7 8 9 10 11 12
12
11
10
9
8
7
6
5
4
3
2
1
0
Months
HR: 0.85 (95% CI = 0.74–0.97), p=0.02
11.0
9.3
Clopidogrel
Ticagrelor
K-M
est
ima
ted
rat
e (%
per
ye
ar)
Steg PG: ESC 2009
PLATO: Stent thrombosis
NEJM: 2009PLATO-STEMI : Stent thrombosis
Steg PG: ESC 2009
K-M
est
imat
ed r
ate
(% p
er y
ear)
0 1 2 3 4 5 6 7 8 9 10 11 12
10
8
6
4
2
0
Months
Clopidogrel
Ticagrelor 9.0
9.3
HR 0.96 (95% CI = 0.83–1.12), p=0.63
PLATO-STEMI Primary safety event: major bleeding
Steg PG: ESC 2009
PCI Recommendations – Class I
(Classe I – Evidenza C) 2008
Ancillary Therapy to Reperfusion (2004)
Unfractionated heparin (UFH) should be given intravenously in:
Patients undergoing PCI or surgical revascularization
After alteplase, reteplase, tenecteplase
After streptokinase, anistreplase, urokinase in patients at high risk for systemic emboli.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Considerazioni finali (1)
La PTCA va considerata sempre e comunque un trattamento “Farmaco-invasivo”
Forse è meglio abbandonare i termini “Facilitata” e “Rescue” perché “potentially misleading labels”: “as-soon-as-possible” o “timely” dovrebbero diventare il nuovo parametro di riferimento.
La trombolisi rimane una buona scelta nei pazienti che si presentano presto con un tempo D2B lungo, con valutazione angiografica “as-soon-as-possible”
Il calcolo del rischio emorragico deve assumere la stessa rilevanza del calcolo del rischio ischemico
Considerazioni finali (2)
Le Linee Guida forniscono elementi utilissimi per la preparazione corretta e l’invio alla PTCA, ma…
…l’implementazione delle stesse va coniugata sempre con…
Condizioni logistiche Fruibilità di risorse adeguate (SUEM 118,
Emodinamica H24 ecc) Condizioni del paziente (classe Killip), insorgenza e
durata dei sintomi, sede dell’infarto, età, rischio emorragico, comorbilità.
GRAZIEGRAZIE
Ospedale Giovanni Paolo II – Lamezia Terme
Lamezia Terme U. O. CARDIOLOGIA con UTIC