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