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TERAPIAANTIPIASTRINICAINCASISPECIFICI:ANZIANI,DM,IRC,NONRIVASCOLARIZZATI
Dr.ssaBuscemiMarialauraDivisionediCardiologiaAziendaOspedalieraSS.AntonioeBiagioeC.Arrigo
CASISPECIFICI?§ Anziani(>75aa)rappresentanoil25%dellapopolazioneconSCA
§ Il30-40%deipazienGricoveraGperSCApresentanoIRCedil20-30%èdiabeGco
§ PazienGnonrivascolarizzaG:40%dellapopolazioneconSCA
Ø OgnigiornocitroviamoadaffrontaredecisioniterapeuGcheinquestedelicatecategoriedipazienG
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
ANALOGIE/DIFFERENZETRAIBLOCCANTIRECETTORIALIDELL’ADPRACCOMANDATI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
CURE:DISEGNODELLOSTUDIO
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Clopidogrel 75mg q.d. + ASA 75-325
mg q.d.* (6259 patients)
Placebo + ASA 75-325 mg q.d.* (6303 patients)
Patients with Acute Coronary
Syndrome
(unstable angina or non-ST-segment
elevation MI)
R
R = Randomization * In combination with other standard therapy The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
3 months ≤ double-blind treatment ≤ 12 months
Clopidogrel 300 mg loading dose
PRIMARYENDPOINT-MI/STROKE/CVDEATH
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Clopidogrel + ASA*
3 6 9
Placebo + ASA*
Months of Follow-Up
11.4%
9.3%
20% RRR P < 0.001
N = 12,562
0 12
* In combination with standard therapy The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
MI/STROKE/CVDEATHWITHIN30DAYS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Clopidogrel + ASA*
10 20 30
Placebo + ASA*
Days of Follow-Up
0
21% RRR P = 0.003
N = 12,562
* In combination with standard therapy The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
Placebo + ASA
N = 6303
Clopidogrel + ASA
N = 6259 End Point
Majorbleeding 2.7% 3.7%
Life-threateningbleeding 1.8% 2.2%
Non-life-threateningbleeding 0.9% 1.5%
Minorbleeding 2.4% 5.1%
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
BLEEDINGRESULTS
CLOPIDOGREL:VARIABILITA’DIRISPOSTA
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Serebruany,JACC2005
NUOVIANTIAGGREGANTI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
!"##$
!"#!$
%&'$()*+,-.*&-&*$(/&)*0$
!"##$
!"#!$
%&'$()*+,-.*&-&*$(/&)*0$
TRITON-TIMI38:studydesignandprimaryefficacyendpoints
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
& Planned PCI
ASA
ASA
Primaryefficacyendpoint:acompositeoftherateofdeathfromcardiovascularcauses,nonfatalMI,ornonfatalstroke
=
UA/NSTEMI (TIMI Risk Score ≥ 3)
STEMI (Primary PCI ≤ 12 hours of symptoms or post-STEMI within 14 days)
R
Prasugrel60mgLD/10mgMD
Clopidogrel300mgLD/75mgMD
Keysecondaryendpointsat30and90daysincludedprimaryefficacyendpointandacompositeoftherateofdeathfromcardiovascularcauses,nonfatalMI,orUTVR
=
14.5monthactualmedian
12.0monthplannedmedian
Double-blindtreatment6-15monthsplannedfollow-up
Keysafetyendpoint:non-CABGrelatedTIMIMajorBleeding
WivioeSDetal.NewEnglJMed2007;357:2001-2015WivioeSDetal.AmHeartJ2006;152:627-635
PRIMARYENDPOINTCVDEATH,MI,STROKE
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
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 0.80 P=0.0003
HR 0.77 P=0.0001
Days
Prim
ary
End
poin
t (%
)
12.1 (781)
9.9 (643)
NNT= 46
ITT=13,608 LTFU=14(0.1%)
STENTTHROMBOSIS(ARCDEFINITE+PROBABLE)
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
0
1
2
0 30 60 90 180 270 360 450
HR 0.48 P <0.0001
Prasugrel
Clopidogrel 2.4 (142)
NNT= 77
1.1 (68)
Days
End
poin
t (%
) AnyStentatIndexPCIN=12,844
TRITON-TIMI38:RATESOFKEYSTUDYENDPOINTS(ALLACS)
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
CABG=CoronaryArteryBypassGrahsurgery;CV=Cardiovascular;MI=MyocardialInfarcGon;TIMI=ThrombolysisInMyocardialInfarcGon
Prasugrel
Clopidogrel
WivioeSDetal.NewEnglJMed2007;357:2001-2015
5
10
15
00 30 60 90 180 270 360 450
Days After Randomization
End
Poi
nt (%
)
120
1.8 (n=111)
2.4 (n=146)
Non-CABG TIMI Major Bleeds
CV Death, MI, Stroke
P=0.03
P<0.001 ↓138 events
↑ 35 events
12.1 (n=781)
9.9 (n=643)
Prasugrel
Clopidogrel
NETCLINICALBENEFITDEATH,MI,STROKE,MAJORBLEED(NONCABG)
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
0
5
10
15
0 30 60 90 180 270 360 450Days
HR 0.87 P=0.004
13.9
12.2
Prasugrel
Clopidogrel ITT=13,608
AllCauseMortalityClop3.2%Pras3.0%P=0.64
End
Poi
nt (%
)
PLATOSTUDYDESIGN
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Primaryendpoint:CVdeath+MI+Stroke
Primarysafetyendpoint:Totalmajorbleeding
6–12-monthexposure
Clopidogrel(n=9291)Ifpre-treated,noaddiGonalloadingdose;ifnaive,standard300mgloadingdose,
then75mgqdmaintenance;(addiGonal300mgallowedprePCI)
Ticagrelor(n=9333)180mgloadingdose,then90mgbidmaintenance;(addiGonal90mgpre-PCI)
NSTE-ACS(moderate-to-highrisk)STEMI(ifprimaryPCI)Clopidogrel-treatedor-naive;
randomisedwithin24hoursofindexevent(N=18,624)
PLATOMAINENDPOINTS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
No. at risk
Clopidogrel
Ticagrelor 9,291
9,333
8,521
8,628
8,362
8,460
8,124
Months
6,743
6,743
5,096
5,161
4,047
4,147 8,219
0 2 4 6 8 10 12
12
11
10
9
8
7
6
5
4
3
2
1
0
13
K-M
est
imat
ed ra
te (
% p
er y
ear)
9.8
11.7
HR 0.84 (95% CI 0.77–0.92), p=0.0003
Clopidogrel
Ticagrelor
WallenGnetal.,NewEngJMed.2009;361:1045–1057
0 2 4 6 8 10 12
10
5
0
15
Clopidogrel
Ticagrelor
11.20
11.58
HR 1.04 (95% CI 0.95–1.13), p=0.434
K-M
est
imat
ed ra
te (
% p
er y
ear)
Months
Primary safety endpoint Primary efficacy endpoint
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 6,545
ALLCAUSEMORTALITY
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
1 2 3 4 5 6 7 8 9 10 11 12
7
6
5
4
3
2
1
0
K-M
est
imat
ed ra
te (%
per
yea
r)
4,201 4,005 3,962 3,876 3,150 2,413 1,993 4,229 4,029 3,989 3,912 3,195 2,471 1,980
Months
No. at risk Ticagrelor Clopidogrel
Clopidogrel
Ticagrelor
4.9
6.0
HR 0.82 (95% CI = 0.68–0.99), p=0.04
ANTIAGGREGANTINELNSTEMI
2014ESC/EACTSGuidelinesonmyocardialrevascularizaCon
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
ANTIAGGREGANTINELLOSTEMITRATTATOCONPCI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
2014ESC/EACTSGuidelinesonmyocardialrevascularizaCon
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
QUALETERAPIAANTIPIASTRINICAORALENEIPAZIENTIANZIANI(>75ANNI)?
ANZIANI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ Lelineeguidasonobasatesutrialcondomsumaschidi60anni.
§ UnaquotamaggioreecrescentedeinostripazienGsonodonnedioltre70anni
§ Bisognatenercontodelleeventualicomorbilità,condizioniassociate(fragilità,declinofunzionaleecogniGvoeladipendenzafisica)
ANZIANI§ PresentaproblemaGchespecifichedaconsiderare,
quali:Ø laridoeamassamagrachepuòcambiareilvolumedidistribuzionedifarmaciidrofilicielipofilici;
Ø ilrallentatotransitointesGnalechepuòcambiarel’assorbimentodeifarmaci;
Ø lapoliterapiachecreaproblemaGchediinterazionifarmacologiche;
Ø lecomorbilità,comeladisfunzionerenalechepuòdeterminarel’accumulodifarmacieliminaGperviarenale
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
QUALESTRATEGIAFARMACOLOGICANEIPAZIENTIANZIANI?
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ CURE:rispeeoaipazienGpiùgiovanilariduzionedelRRdell’incidenzadiendpointprimario(mortevascolare,infartomiocardicoedictus)èrisultataesserepiùaeenuatanell’anziano(13vs29%),anchesepoiciòsitraducevainunasimileriduzionedelrischioassoluto(2.0vs2.2%)
§ DiversistudiosservazionaliefarmacodinamicisuggerisconochetraipazienGanzianiaumentalaresistenzaalclopidogrel
TRITONTIMI38POST-HOCANALYSIS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
BENEFICIOCLINICONETTO:SOTTOGRUPPIADELEVATORISCHIODISANGUINAMENTO
WivioeSetal.NEnglJMed2007:2001-15
PRASUGRELTRILOGYACS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
TRILOGYACS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
PLATOELDERLYPATIENTSUBGROUPANALYSIS:AGE,TREATMENTANDCVTHROMBOTICOUTCOMES
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Events, n Ticagrelor, %
(n=9333) Clopidogrel, %
(n=9291) p for interaction
CV death, MI or stroke ≥75 years old <75 years old
All-cause mortality ≥75 years old <75 years old MI ≥75 years old <75 years old CV death ≥75 years old <75 years old Definite stent thrombosis ≥75 years old <75 years old
471 1399
17.2 8.6
18.3 10.4
293 608
9.8 3.6
12.4 4.8
241 864
9.3 5.4
9.4 6.6
242 549
8.1 3.3
10.3 4.2
25
141
1.8 1.3
2.1 1.9
Ticagrelor better Clopidogrel better
0.22
0.78
0.25
0.90
0.94
0.5 1.0 2.0 0.3 1.5
PLATOELDERLYPATIENTSUBGROUPANALYSIS:ASSOCIATIONOFAGEANDTREATMENTWITHCLINICALOUTCOMES
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
TheriskofbleedingeventsinbothyoungandelderlypaientsisconsistentwiththatobservedintheoverallPLATOtrial[WallenGn2009:I;Husted2011:F,K]
Nointeracionbetweenageandtreatmentwasobserved
Events, n Ticagrelor, %
(n=9333) Clopidogrel, %
(n=9291) p for interaction
Major bleeding ≥75 years old <75 years old
341 1545
14.2 11.2
13.5 10.8
Non-CABG-related major bleeding ≥75 years old <75 years old
183 482
8.3 3.9
7.1 3.2
CABG, coronary artery bypass graft; CI, confidence interval; HR, hazard ratio. Wallentin L, et al. N Engl J Med 2009;361:1045–1057;
Husted S, et al. J Am Coll Cardiol 2011;57:E1099.
Ticagrelor better Clopidogrel better
1.00
0.78
1.0 2.0 0.5 1.5
…QUINDINELPZ>75ANNI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
• Ticagrelor>(o=)Clopidogrel• Prasugrel5mg=Clopidogrel• Prasugrel10mg<Clopidogrel
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
QUALETERAPIAANTIPIASTRINICAORALENEIPAZIENTIDIABETICI?
DIABETICI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ pazienGaffemdaSCAdiabeGcihannotassodimortalitàpiùelevatorispeeoainondiabeGci
§ l’alterazionedelmetabolismoglucidico,l’insufficienzadell’azioneinsulinica,molteplicicondizionimetabolicheedaltreanomaliecellulari(es.aumentatoturnoverpiastrinico,upregulaGondelsegnaleP2Y12estressossidaGvo)provocanoun’intensaamvazionedell’aggregazionepiastrinica
§ resistenzaaifarmacianGaggreganGpiastrinicialmeno4-5voltemaggiorerispeeoainondiabeGci
TRITON-TIMI38.PAZIENTIDIABETICI.N=3146
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
0
2
4
6
8
10
12
14
16
18
0 30 60 90 180 270 360 450
HR 0.70 P<0.001
Days
End
poin
t (%
)
CV Death / MI / Stroke
TIMI Major NonCABG Bleeds
NNT = 21
17.0
12.2
Prasugrel
Clopidogrel
Prasugrel
Clopidogrel 2.6 2.5
SOTTOSTUDIODELPLATO.PAZIENTIDIABETICI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Ticagrelor Clopidogrel
N. a rischio 2326 2113 2045 1959 1593 1199 953 2336 2084 2041 1968 1604 1225 975 6999 6507 6407 6252 5143 3955 3191 6952 6434 6318 6153 5044 3869 3097
Incidenza cumulativa dell’endpoint primario (morte CV, IM, ictus)
End
poin
t prim
ario
0 0
10
5
60 120 240 300 Giorni dalla randomizzazione
20
15
360 180
No diabete Ticagrelor Clopidogrel
Diabete
Fig. 1A e Tab. 4, Rif. g13
Non diabetici: HR: 0,83; IC 95%: 0,74-0,93 (RRR=17%)
Ticagrelor:180mg(dosedacarico),quindi90mgBIDClopidogrel:300-600mg(dosedacarico),quindi75mgOD
Dosiaddizionali:300mgdiclopidogrelprimadellaPCI
Diabetici: HR: 0,88; IC 95%: 0,76-1,03 (RRR=12%)
HbA1c ≥ 6,0% HbA1c < 6,0%
p=0,24
RRR 7%
RRR 20%
HbA1c < 6,0%: ticagrelor 8,2%, clopidogrel 9,0%; HR: 0,93; IC 95%: 0,79-1,09 HbA1c ≥ 6,0%: ticagrelor 11,4%, clopidogrel 14,2%; HR: 0,80; IC 95%: 0,70-0,91
16,2
8,4 10,2
14,1
…QUINDIINPZDIABETICI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ Ticagrelor>Clopidogrel§ Prasugrel>>Clopidogrel
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
QUALETERAPIAANTIPIASTRINICAORALENEIPAZIENTICONINSUFFICIENZARENALE?
INSUFFICIENZARENALECRONICA
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ PazienGconSCAeinsufficienzarenalepresentano:
Ø piùaltamortalità,rischioischemicoerischioemorragicoetalerischioaumentainmanieraesponenzialeneipazienGconfiltratoglomerulare≤30ml/min/1.73m2
Ø rischioditrombosidistentdocumentataoprobabilecirca3.5voltesuperioreallostandard
ANTIAGGREGANTIEINSUFFICIENZARENALE
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
MontalescotCirculaGonsept142010
…QUINDIINPZCONINSUFFICIENZARENALE
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ Ticagrelor>>Clopidogrel§ Prasugrel>=Clopidogrel
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
QUALETERAPIAANTIPIASTRINICANEIPAZIENTINONRIVASCOLARIZZATI?
NONRIVASCOLARIZZATI§ RecenGregistriinternazionalihannodocumentatoche
circail40%deipazienGricoveraGcondiagnosidiSCAricevonountraeamentoconservaGvo
§ duepopolazionidisGnte:Ø pazienGche,acausadelRelevato(pazienGfragiliconmulGplecomorbilità)otroppobasso,nonsononeanchesoeoposGadesamecoronarografico;
Ø pazienGchedopolacoronarografianonvengonorivascolarizzaGperillororischioanatomicotroppobasso(coronaropaGasubcriGcaomalamaostrumvadiunvasosecondario)o,incasipiùrari,perlapresenzadiunacoronaropaGaostrumvatalmenteseveraedestesadaesseregiudicatanonrivascolarizzabile. "
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
ComorbiditiesPatient refusalRevasc.unsuitableDNR statusAdvanced ageActive bleeding Other
20%
18%
17% 16%
11%
4%
14%
ReasonsforcontraindicaionstocardiaccatheterizaionintheCRUSADERegistry
Comorbidiies
(CV death, MI,stroke)
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
PRASUGRELTRILOGYACS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
HR0.91(95%CI,0.79to1.05)p=0.21 HR0.93(95%CI,0.75to1.15)
non inv
HR 0,85 (0,73-1,00), p = 0,045 HR 0,75 (0,61-0,93), p = 0,010
non inv
HR 1,17 (0,98-1,39), p = 0,079
…NELL’UA/NSTEMIESTRATEGIACONSERVATIVA
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
§ Ticagrelor>Clopidogrel§ Prasugrel<o=Clopidogrel
SCELTAANTIAGGREGANTESECONDOG.L.ESC/AHA/ACC
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
*Prasugrelinassenzacontroindicazioni(stroke/TIA) S.D.WivioeLANCETMarch2015
CONCLUSIONI:comemicomportonellapraicaclinica?
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Clopidogrel Prasugrel Ticagrelor
STEMIePCIprimaria + ++ ++UA/NSTEMIePCI + ++ ++UA/NSTEMIestrategiaconservaGva + - ++>75anni + + +(+)DiabeGci + ++ ++PzconTIA/stroke + - +Insufficienzarenale<60ml/min + + ++
GRAZIEDELL’ATTENZIONE
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
SOTTOANALISIDELLOSTUDIOTRITON-TIMI38EVENTICLINICICORRELATIALLOSTATODID.M.
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
WivioeSD,NEnglJMed2007;357(20):2001-15
Ratesofcardiovasculardeath,nonfatalmyocardialreinfarcion,nonfatalstroke,andmajorbleedingwithinthefollow-upperiodinpaientsaged>75yearsenrolledinthePLATO5andTRITON-TIMI386trials.
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
JukemaJW,CurrentMedicalResearch&Opinion Vol.28,No.2,2012,203–211,
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
CONCLUSIONI:RUOLONUOVIANTIAGGREGANTI
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
TICAGRELOR PRASUGRELRIVASCOLARIZZAZIONE
TERAPIAMEDICADIABETICI
PRETRATTAMENTOINSUFF.RENALE
ANZIANIPESO
STROKE/TIAISCHEMICOTAO/NAOMORTALITA’
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
SITID’AZIONEDELTRATTAMENTOANTIPIASTRINICOYousufO,BhaeDL.NatRevCardiol2011:doi:10.1038/nrcardio.2011.96
YousufO,BhaeDL.NatRevCardiol2011:doi:10.1038/nrcardio.2011.96TargetedanGplatelettherapies
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
COMPARINGMEANAGESOFITALIANACSREGISTRIESANDGUIDELINE-BUILDINGTRIALS
TERAPIAANTIPIASTRINICAINCASISPECIFICI Dr.ssaBuscemiMarialaura
Eur Heart J Acute CV Care
2012
80-
75-
70-
65-
60-
55-
NSTEACS STEMI
74 68
BLITZ 4
women
men
Eur Heart J Acute CV Care
2012
68 63
BLITZ 4
women
men
62 62 62
RITA III
Lancet 2002
TIMI 18
NEJM 2001
ICTUS NEJM 2005
60 59
TRITON Lancet 2009
HORIZONS NEJM 2008
PLATO Circulation
2011
59
years
SavonieoS.RevEspCardiol2014;67:564
COURAGEmeanage62SINTAXmeanage65BESTmeanage64