Stefano De Servi 1910 1960 Dipartimento Cardiovascolare ... · ACS patients 296 centres 4 Italian...
Transcript of Stefano De Servi 1910 1960 Dipartimento Cardiovascolare ... · ACS patients 296 centres 4 Italian...
Stefano De ServiDipartimento CardiovascolareAzienda Ospedaliera Ospedale Civile di Legnano
1910 1960
2010
CONFLICT OF INTEREST :
ELI LILLY- DAICHII SANKYO , MERCK, MEDICINES COMPANY, ASTRA ZENECA: Advisory Board Meetings , Speaker’s fees
EmploYEd antithrombotic therapies in patients with acute
coronary Syndromes HOspitalized in iTalian CCUs
Registry
EYESHOT
EYESHOTRegistry
EYESHOT
è un registro nazionale, prospettico, multicentrico ed osservazionale, su pazienti ricoverati consecutivamente con diagnosi di Sindrome Coronarica Acutanelle UTIC italiane , ubicate in ospedali con e senza laboratorio di emodinamica e cardiochirurgia, durante un periodo di 3 settimane , che rispondano ai criteri di inclusione
EYESHOTRegistry
Obiettivi (1)
• Ottenere una serie completa di dati al fine di migliorare le conoscenze sulle varie terapie antitrombotiche comunemente impiegate (da sole o in combinazione), dal momento del ricovero alla dimissione, in pazienti con SCA con differenti profili di rischio ischemico/emorragico e sottoposti a differenti strategie terapeutiche (PCI, CABG, strategia conservativa);
EYESHOTRegistry
Obiettivi (2)
•Valutare i fattori che determinano le scelte delle strategie di gestione delle terapie antitrombotichenella fase acuta dell'evento indice;
• Determinare la frequenza di eventi clinici intra-ospedalieri (ischemici ed emorragici) in un’ampia popolazione del mondo reale di pazienti con SCA ricoverati in UTIC, trattati con diverse strategie di rivascolarizzazione e differenti combinazioni di agenti antitrombotici.
BLITZ
2001
1959
ACS patients
296 centres
4 Italian ANMCO Registries
BLITZ-2
2003
1888
NSTE-ACS patients
275 centres
BLITZ-4
2009-2010
5854
ACS patients
163 centres
EYESHOT
2013
?
ACS patients
243 centres
BLITZ
2001
1959
ACS patients
296 centres
4 Italian ANMCO Registries
BLITZ-2
2003
1888
NSTE-ACS patients
275 centres
BLITZ-4
2009-2010
5854
ACS patients
163 centres
EYESHOT
2013
?
ACS patients
213 centres
In-hospital treatment
Treatment at discharge
BLITZ
2001
1959
ACS patients
296 centres
4 Italian ANMCO Registries
BLITZ-2
2003
1888
NSTE-ACS patients
275 centres
BLITZ-4
2009-2010
5854
ACS patients
163 centres
EYESHOT
2013
?
ACS patients
213 centres
2001, anno cruciale nella storia della Cardiologia moderna
Clopidogrel in non-STE ACS
ESC Guidelines 2002
- Once diagnosed, ACS without persistent ST-segment elevation requires an initial medical treatment including aspirin 75 to 150 mg daily, clopidogrel , LMWH or unfractionated heparin , betablocker and oral or intravenous nitrates in cases of persistent or recurrent chest pain.
ESC Guidelines for nonESC Guidelines for non--STE ACSSTE ACSStrategies accoding to risk stratificationStrategies accoding to risk stratification
Patients with recurrent ischemiaRecurrent chest pain
Dynamic ST-segment changes(ST-segment depression or transient
ST segment elevation)Early post infarction unstable angina
Elevated troponin levelsDiabetes
Hemodynamic instabilityMajor arrhythmias (VF, VT) h
Patients with recurrent ischemiaPatients with recurrent ischemiaRecurrent chest painRecurrent chest pain
Dynamic STDynamic ST--segment changessegment changes(ST(ST--segment depression or transient segment depression or transient
STST segment elevationsegment elevation))Early post infarction unstable anginaEarly post infarction unstable angina
Elevated troponin levelsElevated troponin levelsDiabetesDiabetes
Hemodynamic instabilityHemodynamic instabilityMajor arrhythmias Major arrhythmias (VF, VT)(VF, VT) hh
GpIIB/IIIA blockersGpIIB/IIIA blockers
andand
Coronary angiographyCoronary angiography
Bertrand M et al, Eur Heart J 2002;Bertrand M et al, Eur Heart J 2002;Bertrand M et al, Eur Heart J 2002; 23:1809
BLITZ
2001
1959
ACS patients
296 centres
4 Italian ANMCO Registries
BLITZ-2
2003
1888
NSTE-ACS patients
275 centres
BLITZ-4
2009-2010
5854
ACS patients
163 centres
EYESHOT
2013
?
ACS patients
213 centres
BLITZ
2001
1959
ACS patients
296 centres
4 Italian ANMCO Registries
BLITZ-2
2003
1888
NSTE-ACS patients
275 centres
BLITZ-4
2009-2010
5854
ACS patients
163 centres
EYESHOT
2013
?
ACS patients
213 centres
EYESHOTRegistry
Data Entry
3 settimane: 2-22 Dicembre
Diagnosi iniziale e finaleCaratteristiche clinicheValori di laboratorio e caratteristiche dell’ECGProfilo di rischio (ischemico/emorragico)Modalità del ricovero e durata della permanenza in U TICProcedure diagnostiche e terapeutiche (PCI, CABG o nessuna) Variabili proceduraliEventi clinici intra-ospedalieri (morte, infarto mi ocardico, sanguinamenti maggiori eminori).
Differenti terapie antitrombotiche, comprese le combin azioni, con la loro tempistica, via di somministrazione e dosaggio, dal momento del ricovero alla dimissione, con particolare attenzione a lle modifiche del tipo di farmaco, e/o alla via di somministrazione ed al suo dosaggio nei differenti contesti clinici
Disegno dello Studioe Raccolta Dati
Choices Impacting Anti-Thrombotic Therapy
Cath S
trategy
UFH Biva LMWH
ASA Clopidogrel Prasugrel
NoneAbciximab
Eptifibatide/Tirofiban
New Direct Xa Inhibitors
Cangrelor
Ticagrelor
Fondap.
Timing of Administration
Ris
k P
rofil
e
Aspirin (81-325 mg)
Clopidogrel → Novel P2Y12 inhibitors
LMWH → UFH → Bivalirudin
GP IIb/IIIa inhibitors
Routine post-PCI LMWH
Chronic oral anticoagulation
Stacking: An Unappreciated Enemy
2012
NSTE-ACS
Pre-HospED
CCU
Cath Lab
PCI Post-PCIChronic
Oral Tx
Unknown Anatomy Known Anatomy
Clopidogrel Ticagrelor
When to StartAntiplatelet Rx?
Prasugrel
Upstream Downstream
Prasugrel 30 mg
Prasugrel 60 mg Prasugrel 30 mg
Prasugrel 10 mg or 5 mg (based on weight and age) f or 30 days
PCI
1°Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa bailo ut, at 7 days
Placebo
CoronaryAngiography
n~4100 (event driven)
CoronaryAngiography
PCI
CABG or
MedicalManagement(no prasugrel)
CABG or
MedicalManagement
(no more prasugrel)
Montalescot G et al. Am Heart J 2011;161:650
Randomize 1:1Double-blind
NSTEMI + Troponin ≥ 1.5 times ULN local lab valueClopidogrel naive or on long term clopidogrel 75 mg
ACCOAST Design Schema
Days From First Dose0 5 10 15 20 25 30
End
poin
t (%
)
0
5
10
15
19962037
17881821
17751809
17691802
17621797
17521791
CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout
16211616
No. at Risk, PrimaryEfficacy End Point:No pre-treatmentPre-treatment
Pre-treatment10.810.0
Pre-treatment
Hazard Ratio, 0.997 (95% 0.83, 1.20)P=0.98P=0.81
(95% 0.84, 1.25) Hazard Ratio, 1.02
No Pre-treatment10.8
9.8No Pre-treatment
1° Efficacy End Point @ 7 + 30 days
Montalescot G, et al. N Engl J Med 2013;369:999
All TIMI (CABG or non-CABG) Major Bleeding
Days From First Dose0 5 10 15 20 25 30
End
poin
t (%
)
0
1
2
3
4
5
All TIMI Major Bleeding
Pre-treatment2.9
Pre-treatment2.6
No Pre-treatment1.5
No Pre-treatment1.4
19962037
19471972
13281339
12971310
12881299
12841297
12631280
No. at Risk, All TIMI Major Bleeding:No pre-treatmentPre-treatment
Hazard Ratio, 1.97 (95% 1.26, 3.08)P=0.002
Hazard Ratio, 1.90(95% 1.19, 3.02) P=0.006
Montalescot G, et al. N Engl J Med 2013;369:999
OLD PARADIGM
NEW PARADIGM
CAG + PCI
CAG + PCI *
UFH, ASA, upstream GPIIB IIIA blockers,
UPSTREAM P2Y12 INHIBITOR
ASA, LMWH ( Bivalirudin, UFH) GPIIB IIIA blockers ( selective use),
PRASUGREL ( 60 mg LD ), TICAGRELOR (180 mg LD ) bef ore PCI according to clinical characteristics ( diabetes , risk stent thrombosis, low CrCl, age…)
“ Cooling-off strategy ”
DAYS
HOURS
“ Early invasive approach”
Antithrombotic therapy in NSTE-ACS with planned invas ive strategy
* Immediate or early surgery may be an additional a vailable option
EYESHOT (EmploYE d antithrombotic therapies
in patients with acute coronary S yndromes HOspitalized in iT alian CCUs) Registry
Strategies in NSTE-ACS
Conservative strategy :
ASA + TICAGRELOR on admission
Invasive strategy :
ASA + CLOPIDOGREL 300 mg LD on admission
Switch to PRASUGREL , if PCI in diabetics, or high risk of stent thrombosis
Switch to TICAGRELOR , if CrCl <60 ml/min, Age >74 y, “no option” for revascularization
ESC 2013
Switching of P2Y12 inhibitor in patients with ACS:Insights from the GReek AntiPlatElet Registry (GRAP E)
N = 1280 ACS patients (53.5% STEMI)
N= 434 (91%)UPGRADEClop →→→→Pra/Tica
N= 25 (5%)DOWNGRADEPra/Tica →→→→Clop
N= 18 (4%)CHANGETica↔↔↔↔Pra
Conclusions : In-hospital switching of P2Y12 inhibitor is frequent and mostly represents upgrade from clopidogrel to prasugrel or ticagrelor.
477 (37.3%) SWITCHING
EYESHOTRegistry
250 UTIC rappresentative della realtà italiana (ospedali di ogni livello, in aree metropolitane e
rurali, nel nord, nel centro e nel sud della nazione)
Studio Periodo arruolamento
Popolazione N UTIC n
BLITZ 1 2 settimane STEMI/NSTEMI 296 1959
BLITZ-2 3 settimane NSTEACS 275 1888
BLITZ-3 2 settimane Ricoveri UTIC 332 3636 (solo SCA)
BLITZ-4 10 settimane (fase 1)
STEMI/NSTEMI 163 5915 (fase 1)
n stimato= 2500 pazienti
Influence of Timing of Clopidogrel Treatment on theEfficacy and Safety of Bivalirudin in the ACUITY Tri al
Lincoff AM, et al. J Am Coll Cardiol Intv 2008;1:63 9
Risk ratio: 1.66, 95% CI: 1.05 to 2.63; p=0.03*Death, MI, urgent TVR at 30 days
Guidelines on myocardial revascularizationWijns W, et al. Eur Heart J 2010;31:2501
Guidelines for the management of NSTE-ACSHamm CW, et al. Eur Heart J. 2011 Sep 21. [Epub ahead of print]
ESC Recommendations for Oral Antiplatelet Agents
Rates of Definite Acute ST in Recent Clinical Trial s without Pre-Treatment with APLT
Wiviott SD, et al.N Engl J Med 2007
Bhatt DL, et al.N Engl J Med 2013
Stone GW, et al.N Engl J Med 2007
Comparator ArmsNew Drug
Clopidogrel and Pre-Treatment in PCI: A Meta-Analysis
8608 patients out of 7 RCTs undergoing PCI, including NSTEACS, STEMI, and elective PCI
PCI Cure
Relative Weight, % 43.1 49.7
Bellemain-Appaix A, et al. JAMA. 2012;308:2507
Ab
solu
te r
isk
, %
OR: 0.80P=0.17
OR: 0.77P<0.001NNT: 40
VN
-P2Y
12 P
RU
0
100
200
300
400
clop 600 mg/pras 60 mg
clop 600 mg/pras 30 mg
median
placebo/pras 60 mg
Pharmacodynamic
Endpoints
Primary Endpoint:
PRU at 6 hrs
n= 43 n= 38 n= 45
P=0.188
Diodati J and Angiolillo DJ. Circ Cardiovasc Interv 2013 (in press)
Prasugrel LD Alone vs. Clopidogrel + Prasugrel LDs
PRASUGREL (AM) CLOPIDOGREL (AM)
PRASUGREL LD ALONE CLOPIDOGREL + PRASUGREL LDs
Platelet P2Y12 Receptor
Diodati J and Angiolillo DJ. Circ Cardiovasc Interv 2013 (in press)AM=Active Metabolite; LD=Loading Dose, PD=Pharmacodynamic
4 French AMI registries
30-day mortality in whole AMI population and NSTEMI
USIK 1995 USIC 2000 FAST-MI 2005 FAST-MI 2010Courtesy of N.Danchin
30-day mortality by age in NSTEMI
4 French AMI registries
Courtesy of N.Danchin
NSTEMI:changing characteristics
1995 2000 2005 2010 P value
Age (years) 68.5 ± 14.2 68.9 ± 13.5 70.2 ± 13.4 68.6 ± 13.6 0.71
Diabetes mellitus 20.1 25.8 29.1 27.1 0.002
Current smoking 26 21.9 22.2 24.5 0.74
Obesity 13.4 22.5 21 23.9 <0.001
Previous MI 27.4 28.4 23.8 22.8 0.006
Peripheral artery disease 12 14.7 13.6 11.8 0.57
4 French AMI registries
Courtesy of N.Danchin
Use of PCI during hospital stayNSTEMI
4 French AMI registries
Courtesy of N.Danchin
Use of coronary angiography : 2000 - 2010 NSTEMI
4 French AMI registries
Courtesy of N.Danchin
In-hospital switching in real-life patients with ACS
Alexopoulos A, et al. JACC 2013
Data from GRAPE registry
Alexopoulos A, et al. International Journal of Cardiology 2013
Contemporary use of oral antiplatelet agentsThe GRAPE registry
Bleeding events with new P2Y12 inhibitors in real-life patients
The GRAPE registry
Alexopoulos A, et al. JACC 2013
NSTEMI: antithrombotic therapy in first 48 hours
Courtesy by Danchin
4 French AMI registries
30-day mortality by PCI use
% with PCI: 12.5 44 51 65
Mean age: 68.5 68.9 70.2 68.6
Mean age: 68.5/62.7 72.0/64.9 73.6/67.0 72.3/66.6
NSTEMI
4 French AMI registries
Courtesy of N.Danchin
3-year-survival according to the strategy used
Puymirat E, et al. J AM Coll Cardiol Intv 2012;5:893-902
FAST-MI Registry
3-year-outcomes according to invasive strategy
Puymirat E, et al. J AM Coll Cardiol Intv 2012;5:893-902
FAST-MI Registry
5-year-outcome in elderly by management strategy
Roe MT, et al. Circ Cardiovasc Qual Outcomes 2013;6:323-32
CRUSADE Registry
Puymirat E, et al. J AM Coll Cardiol Intv 2012;5:893-902
Invasive Strategy according to GRACE scoreFAST MI Registry
Ryan JW, et al. Circulation 2005;112:3049-57
CRUSADE registry
Timing of coronary angiography
Bakhai A, et al. Eurointervention 2011;6:992-6
The APTOR observational study
Time from hosp-admission to PCI in NSTEMI
Zeymer U, et al. Eur J Prev Cardiol 2012;20:218-28
Data from 14 european countries
Timing of clopidogrel in ACS undergoing PCI
EYESHOTRegistry
Saranno inclusi tutti i pazienti con diagnosi inizi ale di SCA (NSTE-SCA o STEMI) ricoverati consecutivamente in UTIC nel periodo di osservazione stabilito, sottoposti a rivascolarizzazione miocardica (PCI o CABG) o a trattamento conservativo, che avranno firmato il consenso informato.
Criteri di Inclusione/Esclusione
Bakhai A, et al. Eurointervention 2011;6:992-6
Cumulative frequency of days
from hospital admission to clopidogrel LD in NSTEMI
The APTOR study
Valenti R, et al. Am J Cardiol . In press
Prasugrel vs Clopidogrel
in unprotected left main-PCI using DES
Clopidogrel Prasugrel p value
n=104 n=148
�Age (yrs) 72 ± 11 72 ± 10 .811
� Male 78 (75) 112 (76) .902
� Diabetes 23 (22) 36 (24) .684
� Pre MI 20 (19) 36 (24) .338
� Peripheral Vascular disease 20 (19) 32 (22) .644
� Recent MI (<30 days) 11 (12) 14 (14) .595
� Acute coronary syndrome 61 (59) 103 (70) .073
� LVEF < 0.40 34 (33) 51 (34) .770
� Creatinine > 150 µmol/L 9 (9) 23 (15) .106
� EuroSCORE > 6 55 (53) 84 (57) .553
� EuroSCORE > 13 24 (23) 48 (32) .106
FLORENCE LEFT MAIN-PCI REGISTRY
Valenti R, et al. Am J Cardiol . In press
Prasugrel vs Clopidogrel in unprotected left main-PCI using DES
FLORENCE LEFT MAIN-PCI REGISTRY
One-year clinical outcomes
Invasive Strategy according to risk levelGRACE Registry
Jedrzkiewicz S, et al. Can J Cardiol 2009;25:e370-e376
Gyenes GT, et al. Can J Cardiol 2013
Canadian Global Registry of Acute Coronary Events
Timing of coronary angio by admission day
Mon Tue Wed Thu Fri Sat Sun
Tim
e fr
om
ad
mis
sio
n t
o a
ng
iog
rap
hy,
ho
urs
Day of admission
51,0 49,6 46.6
92.7
71.3
58.9
94.7
Gyenes GT, et al. Can J Cardiol 2013
Canadian Global Registry of Acute Coronary Events
Frequency and timing of coronary angiography by risk status
0
20
40
60
80
100
Weekday
54 h
Co
ron
ary
ang
iog
rap
hy,
per
cen
t
1812 753 756 307 2568 1060
Weekday
70 h
Weekend
69 h
Weekend
72 h
Overall
61 h
Overall
71 h
Low-to intermediate-risk gorup (GRACE score < 141), overall n = 3701
High-risk group (GRACE score ≥ 141), overall n = 2378
P < 0.0001
Time to angiography
69.7
44.7
69.6
45.2
69.7
44.8
Bakhai A, et al. Eurointervention 2011;6:992-6
The APTOR observational study
Location of first clopidogrel LD in ACS patients
Boggon R, et al. Eur Heart J 2011
HR 2.65 (95% CI, 2.17-3.17) for death or MI in the first year post hospital
discharge in case of premature clopidogrel discontinuation
MINAP-GPRD COHORT
Clopidogrel discontinuation after ACS
NSTEMI:NSTEMI:
tra best practice e registritra best practice e registri
Le nuove evidenze della terapia antipiastrinicaLe nuove evidenze della terapia antipiastrinica
Alberto MenozziAzienda Ospedaliero-Universitaria di Parma
Napoli, 2 ottobre 2013
Incidence of myocardial infarction
- Steg PG, et al. Eur Heart J 2012; 33:2569–2619
- Hamm CW, et al. Eur Heart J 2011;32:2999-3054
- Yeh RW, et al. N Engl J Med 2010;362:2155-65
Generalised use of
troponin measurement
STEMI
NSTEMI
5-year-mortality in NSTEMI and STEMI
FAST-MI Registry
Puymirat E, et al. J AM Coll Cardiol Intv 2012;5:893-902
NSTEMIConundrum of clinical situations
Conclusioni• I dati di registro mostrano che, negli anni più recenti, le
raccomandazioni di “best practice” vengono sempre più estesamente
adottate nella pratica clinica, ed in particolare è in aumento la quota di
pazienti sottoposti a strategia invasiva, con inerente beneficio clinico
• Per quanto concerne il timing all’angiografia è verosimile che a
seguito delle linee guida ESC del 2011 vi sia un progressivo
accorciamento delle tempistiche, per lo meno nei centri dotati di
emodinamica
• I dati riguardanti la terapia antiaggregante mostrano discreta adesione
alle linee guida e, per quanto concerne i nuovi antiaggreganti orali e
prasugrel in particolare, mostrano anche nella popolazione “real-
world” dati di efficacia e sicurezza consistenti con quelli degli studi
clinici
Objectives:
- To obtain a complete national data set in order to improve our knowledge on different
antithrombotic therapies commonly employed from admission to discharge in ACS patients
undergoing different therapeutical strategies (PCI, CABG, conservative).
-To assess the rate of in-hospital clinical events (ischemic and hemorrhagic) in a wide real-
world setting of ACS patients admitted in CCUs treated with different revascularization
strategies and combinations of antithrombotic agents.
EYESHOT