sindrome coronarica acuta antiaggreganti: quale molecola
Post on 18-Oct-2021
8 Views
Preview:
TRANSCRIPT
Sindrome Coronarica Acuta
Antiaggreganti: quale molecola, quale paziente, quale durata?
Alessandra Chinaglia
Antiaggreganti piastrinici
Quale molecola ?
ASPIRINA
+
P2Y12 receptor inhibitor
Quale molecola ?Caratteristiche degli antagonisti del recettore piastinico P2Y12 orali
SerebruanySerebruany, JACC 2005, JACC 2005
Quale molecola ?Caratteristiche degli antagonisti del recettore piastinico P2Y12 orali
SerebruanySerebruany, JACC 2005, JACC 2005
Variability in plateletresponsiveness to clopidogrel
Ticagrelor ha maggiore attività antipiastrinica rispetto a clopidogrel ?
Clopidogrel-nonresponsive patients Clopidogrel-responsive patients
* P < 0.0001, † P < 0.001, ‡ P < 0.05* P < 0.0001, † P < 0.001, ‡ P < 0.05
Gurbel, Circulation. 2010;121:1188-1199
Quale paziente ?
Età avanzataAlto rischio emorragico
Insufficienza renaleDiabete mellito
SCA
NSTEMI STEMI
PCI PPCI FibrinolisiChirurgia Terapia medica
SCA
STEMI nSTEMI
PCI Non PCI
N Engl J Med 2001;345: 494-502
SCA
STEMI nSTEMI
PCI Non PCI
N Engl J Med 2007;357:2001-15
SCA
STEMI nSTEMI
PCI Non PCI
SCA
STEMI nSTEMI
PCI Non PCIX
N Engl J Med 2012;367:1297-309N Engl J Med 2009;361:1045-57
CLOPIDOGREL PRASUGREL TICAGRELOR
Triton TIMI 38PRASUGREL vs CLOPIDOGREL
Primary study endpoint: cardiovascular death, myocardial infarction, stroke
Wiviott, NEJM 2007; 357; 20: 2001
Unstable angina or NSTEMI : 74%
PCI: 99% STENT 94%
CV DeathNonfatal MI
Nonfatal Stroke All Cause Death UTVR Stent Thrombosis
Wiviott SD et al. New Engl J Med 2007;357:2001-2015
TRITONTRITON--TIMI 38: TIMI 38: Major Efficacy End Points at 15 Months (All ACS)Major Efficacy End Points at 15 Months (All ACS)
HR 0.76 P<0.001
HR 0.89 P=0.31
HR 1.02 P=0.93
HR 0.95 P=0.64
(n=6,795)
(n=6,813)
End
Poin
t (%
)
HR 0.66 P<0.001
HR 0.48 P<0.001
2.12.4
7.3
9.5
1.01.0
3.03.2
2.5
3.7
1.1
2.4
TRITON-TIMI 38: Non-CABG TIMI Major Bleeds at 15 Months (All ACS)
Non-CABGTIMI Major
TIMI Major Spontaneous
TIMI Major Related to Instrumentation
TIMI Major Trauma
(n=6,716)
(n=6,741)
Subsets of Non-CABG TIMI Major
1.8%n=111
P=0.032.4%n=146
0.6%n=38
0.7%n=45
0.2%n=12
0.2%n=9
1.1%n=61
1.6%n=92
P=0.45
P=0.01
P=0.51
Wiviott SD et al. New Engl J Med 2007;357:2001-2015
Endp
oint
(%)
PLATOTicagrelor vs clopidogrel
Morte cardiovascolare,infarto miocardico, stroke
9.8%11.7%
N Engl J Med 2009;361:1045-57
Unstable angina or NSTEMI : 62%
PCI: 61%
PLATOACS (37% STEMI – NSTEMI)
Ticagrelor vs clopidogrel
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
Total major bleeding
NS
NS
NS
NS
NS
0
K-M
est
imat
ed ra
te (%
per
yea
r)
PLATO major bleeding
1
2
3
4
5
6
7
8
9
10
12
11
13
TIMI major bleeding
Red cell transfusion *
PLATO life-threatening/
fatal bleeding
Fatal bleeding
TicagrelorClopidogrel
Major bleeding and major or minor bleeding according to TIMI criteria refer to nonadjudicated events analyzed with the use of a statistically programmed analysis in accordance with definition described in (Wiviott SD et al. NEJM. 357:2001-2015); *Proportion of patients (%); NS = not significant
11.611.2
7.9 7.7
8.9 8.9
5.8 5.8
0.3 0.3
Wallentin L et al. N Engl J Med. 2009 Sep 10;361(11):1045-57
Non-CABG and CABG-related major bleeding
p=0.0264
p=0.0246
NS
NS
9K
-M e
stim
ated
rate
(%
per
yea
r)
Non-CABGPLATO major
bleeding
8
7
6
5
4
3
2
1
0Non-CABGTIMI major bleeding
CABGPLATO major
bleeding
CABG TIMI major bleeding
TicagrelorClopidogrel
4.5
3.8
2.8
2.2
7.4
7.9
5.3
5.8
Wallentin L et al. N Engl J Med. 2009 Sep 10;361(11):1045-57
NSTEMI sottoposto a PCI ?
Cannon, Lancet 2010
Cardiovascular death, myocardial infarction, or stroke
p=0·0025
PCI: 77 %
NSTEMI sottoposto a PCI ?
Cannon, Lancet 2010
All cause death p=0·0025
PCI: 77 %
Cannon, Lancet 2010
Quale paziente ?
Età avanzataAlto rischio emorragico
Insufficienza renaleDiabete mellito
SCA
NSTEMI STEMI
PCITICAGRELORPRASUGREL
PPCI FibrinolisiChirurgia0 Terapia medica
N Engl J Med 2012;367:1297-309
Hazard ratio 0.75, 0.61 to 0.93; P=0.01
James, BMJ 2011;342
Quale paziente ?
Età avanzataAlto rischio emorragico
Insufficienza renaleDiabete mellito
SCA
NSTEMITICAGRELOR STEMI
PCITICAGRELORPRASUGREL
PPCI FibrinolisiChirurgia0
Terapia medicaTICAGRELOR
CLOPIDOGREL
NSTEMI ad alto rischio (anziani) ?
Husted, Circ Cardiovasc Qual Outcomes, 2012 Sep 1;5(5):680-8
Cardiovascular death/MI/stroke All cause mortality
Husted, Circ Cardiovasc Qual Outcomes, 2012 Sep 1;5(5):680-8
Major bleeding Non-CABG-related bleeding
26
RRR 38%
RRR 19%
James, Circulation published online May 9, 2012
NSTEMI con pregresso TIA/stroke ?
27James, Circulation published online May 9, 2012
Quale paziente ?
Età avanzata: TICAGRELOR, CLOPIDOGRELAlto rischio emorragico: TICAGRELOR, CLOPIDOGRELInsufficienza renaleDiabete mellito
SCA
NSTEMI STEMI
PCITICAGRELORPRASUGREL
PPCI FibrinolisiChirurgia0
Terapia medicaTICAGRELOR
CLOPIDOGREL
Circulation. 2010;122:1056-1067
HR 0.77; 95% CI 0.65 to 0.90
17%
22%
7,9%
8,9%
HR, 0.72; 95% CI,0.58 to 0.89
10%
14%
Circulation. 2010;122:1056-1067
15.1%
14.3%;
HR, 1.07; 95% CI, 0.88 to 1.30
8.5%
7.3%
HR, 1.28; 95% CI, 0.97 to 1.68
Quale paziente ?
Età avanzata: TICAGRELOR, CLOPIDOGRELAlto rischio emorragico: CLOPIDOGREL, TICAGRELORInsufficienza renale: TICAGRELORDiabete mellito:
SCA
NSTEMI STEMI
PCITICAGRELORPRASUGREL
PPCI FibrinolisiChirurgia0
Terapia medicaTICAGRELOR
CLOPIDOGREL
Wiviott, Circulation. 2008;118:1626-1636
NNT : 13 DM on insulin, 26 DM not on insulin, 71 no DM
Cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
Wiviott, Circulation. 2008;118:1626-1636
James, EurHJ, August 29, 2010
NSTEMI ad alto rischio (diabete) ?
James, EurHJ, August 29, 2010
Quale paziente ?
Età avanzata: TICAGRELOR, CLOPIDOGRELAlto rischio emorragico: CLOPIDOGREL, TICAGRELORInsufficienza renale: TICAGRELORDiabete mellito: PRASUGREL
SCA
NSTEMI STEMI
PCITICAGRELORPRASUGREL
PPCI FibrinolisiChirurgia0
Terapia medicaTICAGRELOR
CLOPIDOGREL
SCA
STEMI nSTEMI
PCI Non PCI
N Engl J Med 2001;345: 494-502
SCA
STEMI nSTEMI
PCI Non PCI
N Engl J Med 2007;357:2001-15
SCA
STEMI nSTEMI
PCI Non PCI
SCA
STEMI nSTEMI
PCI Non PCIX
N Engl J Med 2012;367:1297-309N Engl J Med 2009;361:1045-57
CLOPIDOGREL PRASUGREL TICAGRELOR
Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke cardiovascular death, non-fatal myocardial infarction, urgent target vessel revascularisation
Stent thrombosis TIMI major bleeding unrelated to CABG surgery
Lancet 2009; 373: 723–31
3534 pazientiPCI 97%
7544 pazientiPCI 82%
HR, 1.63; 95% CI, 1.07 to 2.48; P<0.02
HR, 0.87; 95% CI, 0.75 to 1.01; P<0.07
HR, 0.83; 95% CI, 0.67 to 1.02; P0.07
HR, 0.80; 95% CI, 0.65 to 0.98; P0.03
Quale paziente ?
Età avanzata: TICAGRELOR, CLOPIDOGRELAlto rischio emorragico: CLOPIDOGREL, TICAGRELORInsufficienza renale: TICAGRELORDiabete mellito: PRASUGREL
SCA
NSTEMI STEMI
PCITICAGRELORPRASUGREL
PPCIPRASUGRELTICAGRELOR
FibrinolisiChirurgia0
Terapia medicaTICAGRELOR
CLOPIDOGREL
Quanto è rapida l’inibizione piastrinica dopo il carico ?
Am Heart J 2007;153:66.e9266.e16 Circulation. 2009;120:2577-2585
Parodi, JACC 2013;61:1601–6
Alexopoulos Circ Cardiovasc Interv. 2012;5:797-804
Pre-hospital vs In-hospital Initiation of Ticagrelor Therapy in STEMI PatientsPlanned for Percutaneous Coronary Intervention (ATLANTIC) study
Bhatt, N Engl J Med, March 10 2013
Death from any cause,myocardial infarction, ischemia-driven revascularization, stent thrombosisat 48 hours after randomization
Quale durata ?CLOPIDOGREL
PRASUGREL
TICAGRELOR
30 day and 31–365 day mortality after first time hospitalisation for myocardial infarction between 1984 and 2008
in a Danish nationwide cohort study
Schmidt et al. BMJ 2012
Mortalità complessiva al fup a 6 mesiInH su tutti i pz, a 30 gg e a 6 mesi su quelli con dato disponibile
8,2% 7,5%
Quale molecola ?Caratteristiche degli antagonisti del recettore piastinico P2Y12 orali
reversibileNOTicagrelor
2-4 ore75-85%irreversibileSIPrasugrel
2 ore40-60%irreversibileSIClopidogrel
Tempo dal caricoIPA massimaLEGAMEProfarmaco
Variability in platelet responsiveness to clopidogrel
SerebruanySerebruany, JACC 2005, JACC 2005
Coronarografia: 43.7 %CABG 16.5 %PCI 21.2 %
CUREDeath from Cardiovascular Causes, Nonfatal Myocardial Infarction, Stroke
N Engl J Med 2001;345: 494-502
COMMIT Lancet 2005;366:1607-21
COMMIT: CLOPIDOGREL 75 mg (non carico)45852 pazienti trattati con aspirina e fibrinolisi (54%) o non riperfusi
Morte, Re-IMA o Stroke
CLARITY: clopidogrel 300 vs placebo3491 pazienti < 75 anni trattati con fibrinolisi + aspirina
End Point: Death from Cardiovascular causes, Recurrent Myocardial Infarctionor Recurrent Ischemia Leading to the Need for Urgent Revascularization.
Sabatine, NEJM, 352;12; 2005: 1179
14.1%
11.6%
P=0.03
58
EventTicagrelor,%
(n=2601)Clopidogrel, %
(n=2615) p valueCV death, MI or stroke 12.0 14.3 0.045
MI 7.2 7.8 0.555
CV death 5.5 7.2 0.019
All-cause death 6.1 8.2 0.010
Non-CV death 0.6 1.0 0.252
Stroke 2.1 1.7 0.162
CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; NSTEMI, non-ST-segment elevated myocardial infarction; UA, unstable angina.James S, et al. BMJ 2011;342:d3527.
[James 2011:K]
Clopidogrel betterTicagrelor better
1.0 2.00.2
HR (95% CI)
NSTEMI sottoposto a PCI ?PLATO intent for non-invasive management
NSTEMI
STRATEGIA CONSERVATIVA
PRASUGREL
PCI
TICAGRELORCLOPIDOGREL
DiabeteGiovane
Alto rischioInsufficienza renale
Età avanzataPeso<60 kg
TICAGRELOR
Alto rischioemorragico
TAOPeso<60 kg
CLOPIDOGREL
TICAGRELORCLOPIDOGREL
top related