Francesco Chiarella Ospedale S.Corona Pietra Ligure STEMI PREPARAZIONE ALLA ANGIOPLASTICA NEGLI...

Francesco ChiarellaOspedale S.Corona

Pietra Ligure

STEMIPREPARAZIONE ALLA ANGIOPLASTICANEGLI OSPEDALISENZA EMODINAMICA

La preparazione alla PTCA nelle SCA

PREPARAZIONE FARMACOLOGICA ALLA PTCA:DALLE LINEE GUIDA AI DATI DEGLI STUDI E DEI REGISTRI

PAF 2010

CENSIMENTO 2005

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

PVA

LBZ TN

V FLG ER

Nord TO

UMR LZ A

Centr

o MO CM PGB

CL SI SA Sud

Italia

1 UTIC / 136.500 ab. 1 letto UTIC / 21.816 ab.

5° Censimento Federativo Strutture Cardiologiche

HUB 177

4

15,2

2,3

2

2,3

4,9

5,9

63

0 20 40 60 80 100

118

Altro Ospedale

Altro Reparto

Rep. Chirurgico

Rianimazione

Rep.Medico

Cardiologia

PS/DEA

BLITZ-3: provenienza ricoveri UTIC

PREPARAZIONE FARMACOLOGICA A PTCA OSPEDALI SENZA EMODINAMICA:DALLE LINEE GUIDA AI DATI DEGLI STUDI E DEI REGISTRILinee Guida: rielaborazioni annuali su STEMI e PCI da Comitati Congiunti di 5 Società Scientifiche

IMPRESCINDIBILITA’ DI PROTOCOLLI CONDIVISI

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

UPDATE

2009

Ogni comunità deve sviluppare un protocollo (“sistema di cure”) per lo STEMI

Team multidisciplinare• Sistema Emergenza Territoriale• Ospedale/i no Cath-Lab (“Spoke”)• Ospedale/i con Cath Lab (“Hub”)

ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update

A ciascun Pz il suo percorsoA ciascun Pz il suo trattamento

QUALE FARMACO?


Pathway: Triage and Transfer for PCI (in STEMI)

2009 STEMI Focused Update. Appendix 5

STEMI patient who is acandidate for reperfusion

Initially seen at a PCIcapable facility

Initially seen at a non-PCIcapable facility

Send to Cath Lab for primary PCI(Class I, LOE:A)

Transfer for primary PCI(Class I, LOE:A)

Initial Treatmentwith fibrinolytictherapy (Class 1, LOE:A)

Prep antithrombotic (anticoagulantplus antiplatelet) regimen

Diagnostic angio

Medicaltherapy only

PCI CABG

NOT HIGH RISK

Transfer to a PCI facility may be considered (Class IIb, LOE:C), especially if ischemic symptoms persist and failure to reperfuse is suspected

HIGH RISKTransfer to a PCI facility is reasonable for early diagnostic angio & possible PCI or CABG (Class IIa, LOE:B),

High-risk patients as defined by 2007 STEMI Focused Update should undergo cath (Class 1: LOE B)

Tempo da angor > 3 h Tempo al pallone < 1 h

Alto score di rischio / rischio emorragico

Tempo da angor < 3 h Tempo al pallone > 1 h

Basso score rischio / no rischio emorr.

A tutti prima possibile:

Update 2009

8

La dose di carico di tienopididine è raccomandata per tutti

STEMIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIClopidogrel almeno 300 – 600 mg appena possibile a tutti i pazienti avviati a PCI primaria o non primaria.


Studi di dose finding hanno dimostrato che aumentando il dosaggio si inibiscono PTL più rapidamente, 300600900, ma la sicurezza e l’efficacia clinica non sono ancora rigorosamente stabilite,

Limitazioni: età > 75 storia di TIA o stroke, “active bleeding” urgente BPAC anticoagulanti peso < 60 Kg

STEMI PCI primaria

Prasugrel 60 mg should be given

as soon as possible for

primary PCI.

MODIFIED Recommendation


STEMI: PREPARAZIONE ALLA ANGIOPLASTICANEGLI OSPEDALISENZA EMODINAMICA

entra

PRASUGREL

10

TRITON-TIMI 38

Double-blind

ACS (STEMI 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= 13,600

Wiviott SD et al AHJ 152: 627,2006Adapted with permission from E.Antman

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)P=0.0004

Prasugrel

Clopidogrel

Days

En

dp

oin

t (%

)

12.1

9.9

HR 1.32(1.03-1.68)P=0.03

Prasugrel

Clopidogrel1.82.4

138 events

35 events

Balance of Balance of Efficacy and SafetyEfficacy and Safety

CV Death / MI / Stroke

TIMI Major NonCABG Bleeds

NNT = 46

NNH = 167Adapted with permission from Wiviott SD et al

NEJM 357:2007

TRITON: Results

The number of subjects who would need to be treated to result in one excess major bleed (NNH) was 167

Trattare 46 x prevenire un evento

Trattare 167 x causare un bleeding

12

0

5

10

15

0 30 60 90 180 270 360 450

Per

cen

t (%

)

Days From Randomization

9.5%

6.5%

HR 0.68(0.54-0.87)

P=0.002

12.4%

10.0%

HR 0.79(0.65-0.97)

P=0.02

Clopidogrel

Prasugrel

NNT = 42

CV Death / MI / Stroke

TIMI Major NonCABG Bleeds

Clopidogrel

Prasugrel 2.4

2.1

STEMI CohortSTEMI CohortN=3534N=3534

Montalescot et al Lancet 2008.Adapted with permission from Antman EM.

TRITON TIMI-38

13

0

2

4

6

8

0 1 2 3

1

0

3060 90 180 270 360 450

HR 0.82P=0.01

HR 0.80P=0.003

5.6

4.7

6.9

5.6

Days

Pri

ma

ry E

nd

po

int

(%)

Prasugrel

Clopidogrel

Prasugrel

Clopidogrel

Loading Dose Maintenance Dose

Timing of BenefitTiming of Benefit(Landmark Analysis - 3 days)(Landmark Analysis - 3 days)

Adapted with permission from Antman EM JACC 2008.

TRITON TIMI-38

For STEMI undergoing non-primary PCI carico prasugrel dopo coronarografia pre-PTCA

( entro 1 h)

14

the following regimens are recommended:

If the patient did not receive fibrinolytic therapy…c. …eithereither a loading dose of 300-600 mg of

clopidogrel should be given or,

once the coronary anatomy is known and PCI is planned, a loading dose of 60 mg of prasugrel should be given promptly and no later than 1 hour after the PCI.


MODIFIED

Rec


Ticagrelor !

PLATO: 18.624 STEMI e NSTEMI random ticagrelor vs clopidogrel (180-mg loading dose, 90 mg twice daily thereafter) (300-to-600-mg loading dose, 75 mg daily thereafter). NEJM, 361:1045-1057 2009

antagonist of recettore adenosinico P2Y12

PCI “facilitata” e “rescue”: termini obsoleti (molto attuali)

• I termini “facilitated PCI” e “rescue PCI” non dovrebbero più essere usati

• “ Contemporary therapeutic choices leading to reperfusion for pts with STEMI can be described without these potentially misleading labels”

Cambio concettuale: la riperfusione è l’obiettivo, non si parlerà più di “facilitazione” e di “rescue”, termini giudicati confondenti e obsoletiche siamo invitati a mandare in cantina


CARESS Transfer-

AMI

FINESSE

per testare fibrinolisi+PCI subito vs fibrinolisi + PCI rescue

Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in nAMI (TRANSFER-AMI)

Combined Abciximab REteplase Stent Study in AMI

per testare ½ fibrinolisi +

ABCX + PCI

>

>

STEMI alto rischio

CARESS-IN-AMI: DISEGNATO ALLA RICERCA DEL MIGLIORE TRATTAMENTO

PER I PZ CON STEMI NEGLI OSPEDALI NO CATH-LAB

• 600 STEMI – <75 years old – > 1 high risk feature – RETEPLASE ½ dose, ABCX, heparin,

ASA

• Randomizzazaione a trasferimento immediato x pci o trasferimento x rescue o differito

“Not a trial of facilitated angioplasty opposed to primary angioplasty”

CARESS-IN-AMI: Primary OutcomeSTEMI con immediata PCI: minor numero di eventi avversi a 30 gg Non differenze significative di sanguinamenti

10.7%

4.4%

Di Mario et al. Lancet 2008;371.

CARESS: legittima reteplase metà dose, ABCX, eparina, ASA e poi trasferire

RETEPLASE ½ dose,ABCX, heparin, ASA

TRANSFER-AMIStudio di strategia farmacoinvasiva in 1059 STEMI alto rischiogiunti entro 12 ore da esordio ad ospedale senza cathlab

A tutti: - TNK standard-dose, ASA, UFH or enoxaparin - Clopidogrel loading 300 mg for pts < 75 age 75 mg for pts >75 age Giunti nel Centro con CathLab:- GP IIb/IIIa receptor antagonists according to institutions’ standard practice

Cantor et al. N Eng J Med 2009;360:26.

DISEGNO: TNK STANDARD E PCI ENTRO 24 H VERSUS

TTNK STANDARD E PCI DIFFERITA > 24 H

2.8 hrs

32 hrs

PCI RISULTERA’

TRANSFER-AMI: CONCLUSIONI

In STEMI ad alto rischio che si presentano a Ospedale Spoke:

- fibrinolisi con TNK dose standard , clopidogrel - trasferimento a Hub per eseguire subito angiografia

e PCI “without waiting to determine whether reperfusion has

occurred”

. Cantor et al. N Eng J M 2009;360:26.

23

Recommendations for the Use of Glycoprotein IIb/IIIa Receptor Antagonists in

STEMI

E’ RAGIONEVOLE INIZIARE IL TRATTAMENTO CON ANTI IIb/IIIa AL MOMENTO DI ANGIOPLASTICA (CON O SENZA STENTING)

abciximab

tirofiban, eptifibatide

Use of Glycoprotein IIb/IIIa Receptor Antagonists in STEMI



Modified Recommendation

Use of Glycoprotein IIb/IIIa Receptor Antagonists in STEMI

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII L’UTILITA’ DI ANTI IIb/IIIa COME

STRATEGIA FARMACOLOGICA DI

PREPARAZIONE ALLA

ANGIOPLASTICA prior to arrival

in the cardiac catheterization

laboratory for angiography and

PCI is uncertain.


I risultati del FINESSE pubblicati dopo le Linee Guida riaccendono la disputa

pre-PCI ½ -dose lytic + ABCXpre-PCI ABCX alone ABCX at time of PCI

FINESSE: Study design

Ellis et al. N Eng J Med. 2008;358:2205-2217.

TreatmentPre-PCI treatment with ½ -dose lytic plus abciximab, pre-PCI abciximab alone, and abciximab at time of PCI

InclusionSuspected acute MI (ST change or LBBB) within 6 h of symptom onset

ExclusionLow risk (<60 yo, localized inferior infarct) high risk for bleeding

1° OUTCOMES Death, VF after 48 hours, shock, CHF within 90 days

Considerando solo “alto rischio, tempo

< 4 ore”

N = 2452

N = 397

Meno morti a 1 anno !

29

Recommendations for

Use of Parenteral Anticoagulants in Patients

with STEMI

Use of Parenteral Anticoagulants in STEMI


a. UN BOLO AGGIUNTIVO DI EPARINA NON FRAZIONATA PER I PZ CHE GIA’ LA ASSUMEVANO per mantenere un adeguato regime di scoagulazione (misurare ACT)

IL TRATTAMENTO ANTICOAGULANTE RACCOMANDATO

NEGLI STEMI PTCA PRIMARIA

INCLUDE:III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

b. BIVALIRUDINA , CON O SENZA PRECEDENTE EPARINAIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Enoxaparin and fondaparinux unchanged from 2007 STEMI Focused Update

31

HORIZONS-AMI: Design

Stone et al. N Eng J Med. 2008;358:2218-30.

3602 patients with STEMI & symptom onset ≤ 12 hours

randomized

1800 received bivalirudin alone*1802 received heparin +

GP IIb/IIIa inhibitor

Principal management strategyPrimary PCI, 1678 (93.2%)

Deferred PCI, 5 (0.3%)CABG, 23 (1.3%)

Medical management, 94 (5.2%)

Principal Management Strategy Primary PCI, 1662 (92.2%)

Deferred PCI, 3 (0.2%)CABG, 40 (2.2%)

Medical Management, 97 (5.4%)

Emergency angiography Emergency angiography

Endpoints: Composite of net adverse clinical events (NACE)

Included major bleeding plus MACE (a composite of CVD death, reinfarction, target-

vessel revascularization for ischemia, and stroke within 30 days)•

HORIZONS-AMI: Time-to-Event Curves through 30 days: Net Adverse Clinical

Events

Meno eventi avversi a 30 gg con bivalirudina da solapiuttosto che con eparina non frazionata + anti IIb/IIIa


HR=0.75, (0.62-0.92); p=0.006]

QS STUDIO MOTIVA INDICAZIONE CLASSE I

3602 patients with STEMI & symptom onset ≤ 12 hours randomized

1802

1800

HORIZONS-AMI: Time-to-Event Curves through 30 days: Major Bleeding

HR=0.59 (0.45-0.76) p<0.0001


Meno sanguinamenti a 30 gg con bivalirudina da solapiuttosto che con eparina non frazionata + anti IIb/IIIa

HORIZONS-AMI: Results (cont.)

• Treatment with bivalirudin compared with UFH plus GP IIb/IIa inhibitors resulted in significantly lower: – 30-day death rates from cardiac causes (1.8% vs. 2.9%;

RR 0.62; 95% CI 0.40 to 0.95; p=.03), &– 30-day death from all causes (2.1% vs. 3.1%; RR 0.66;

95% CI 0.44 to 1.00; p=0.047)

• At one year, MACE rates were identical, but there was a decrease in all-cause mortality

with bivalirudin (3.4% versus 4.8%, p=0.03).

Use of Parenteral Anticoagulants in STEMI


IL TRATTAMENTO ANTICOAGULANTE RACCOMANDATO NEGLI STEMI PTCA PRIMARIA INCLUDE:

b. BIVALIRUDINAIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Enoxaparin and fondaparinux unchanged from 2007 STEMI Focused Update

• Unfractionated heparin (UFH) administration guided

by:

– Therapeutic activated clotting time (ACT) levels

– Prior administration of GP IIb/IIIa receptor antagonists

Enoxaparin and fondaparinux unchanged from 2007

Enoxaparin, if the last subcutaneous dose was administered at least 8 to 12 hours earlier, an IV (intravenous) dose of 0.3 mg/kg of enoxaparin should be given; if the last subcutaneous dose was administered within the prior 8 hours, no additional enoxaparin should be given. (Level of Evidence: B) Fondaparinux, administer additional intravenous treatment with an anticoagulant possessing anti-IIa activity, taking into account whether GP IIb/IIIa receptor antagonists have been administered. (Level of

Evidence: C)

STEMI PREPARAZIONE ALLA ANGIOPLASTICA NEGLI OSPEDALI SENZA EMODINAMICA

TIENOPIRIDINE (Clopid. 300, Pras 60)

TNK + EPARINA + IIbIIIa in sala

RETEPLASE ½ + ABCX

RETEPLASE ½ + ABCX o solo ABCX o ABCX in cathLab

BIVALIRUDINA

TRITRON TIMI 38

TRANSFER-AMI

CARESS

FINESSE

HORIZONS AMI

Francesco Chiarella Ospedale S.Corona Pietra Ligure STEMI PREPARAZIONE ALLA ANGIOPLASTICA NEGLI...

Documents

Transcript of Francesco Chiarella Ospedale S.Corona Pietra Ligure STEMI PREPARAZIONE ALLA ANGIOPLASTICA NEGLI...