Data: 9 Novembre 2012 Evento: Genova Titolo: added value of GPIIb/IIIa RB in ACS Autore: Stefano...

Data: 9 Novembre 2012

Evento: Genova

Titolo: added value of GPIIb/IIIa RB in ACS

Autore: Stefano Savonitto

Il valore aggiuntodegli anti GPIIb/IIIanella terapia delle SCA

Stefano SavonittoStefano Savonitto

Divisione di CardiologiaDivisione di CardiologiaIRCCS Arcispedale S. Maria NuovaIRCCS Arcispedale S. Maria Nuova

Reggio EmiliaReggio Emilia


Evento: Genova



ACS with persistent ST-segment elevation


Evento: Genova



Time from symptom onset to reopening of the IRAand myocardial salvage


Evento: Genova



Silvain J. JACC 2011;57:1359Silvain J. JACC 2011;57:1359


Evento: Genova



Valgimigli M, et alValgimigli M, et al

Prasugrel vs Tirofiban HBD in PCI for STEMIPrasugrel vs Tirofiban HBD in PCI for STEMI

Variability of platelet inhibitory effect30’ after drug administration


Evento: Genova



All-Cause Mortality 1-Year

open label & double-blind, n = 1398

On-TIME-2

Ten Berg J. J Am Coll Cardiol. 2010;55:2446-55.Ten Berg J. J Am Coll Cardiol. 2010;55:2446-55.


Evento: Genova



A: all ptsN= 2,452A: all ptsN= 2,452

B: TRS>3N= 1,229B: TRS>3N= 1,229

C: TRS>3spoke site N= 502

C: TRS>3spoke site N= 502

D: TRS>3spoke site symptomto rand.< 4hN= 397

D: TRS>3spoke site symptomto rand.< 4hN= 397

6.6%6.6%

13.3%13.3%

16.0%16.0%

Herrmann HC. JACC Intv 2009;2:917-24Herrmann HC. JACC Intv 2009;2:917-24

Benefit of facilitated PPCI in high-risk patients presenting at non-PCI centersBenefit of facilitated PPCI in high-risk patients presenting at non-PCI centers

1-year mortality1-year mortality


Evento: Genova



Time from symptom onset to reopening of the IRAand myocardial salvage

JACC Intv 2010; 3: 1292-4JACC Intv 2010; 3: 1292-4

ON TIME 2 Ortolani FINESSE

“Educating the public to seek treatment at an early stage… is likely to reduce mortality to a greater degree than pharmacological facilitation before PCI, although translation of this goal to reality in a community setting is and will continue to be extremely difficult.”

“Educating the public to seek treatment at an early stage… is likely to reduce mortality to a greater degree than pharmacological facilitation before PCI, although translation of this goal to reality in a community setting is and will continue to be extremely difficult.”


Evento: Genova



Heestermans AACMJ Thrombosis Haemostasis

2009;7:1612 -8

Reduction of early stent thrombosis with pre-hospital high-dose tirofiban in STEMI

Reduction of early stent thrombosis with pre-hospital high-dose tirofiban in STEMI


Evento: Genova



Acute Stent Thrombosis

0.3% 0.3%

1.5% 1.5%

HR (95%CI) =HR (95%CI) =5.93 [2.06,17.04]5.93 [2.06,17.04]

P = 0.0002P = 0.0002

16111611 15831583 15801580 15781578 1577157715911591 15871587 15841584 15831583 15831583

Number at riskNumber at riskBivalirudinBivalirudin

UFH+GPIIb/IIIaUFH+GPIIb/IIIa

Def

/Pro

b S

tent

Thr

ombo

sis

(%)

Def

/Pro

b S

tent

Thr

ombo

sis

(%)

0.00.0

0.50.5

1.01.0

1.51.5

2.02.0

2.52.5

3.03.0

3.53.5

Time in HoursTime in Hours

00 66 1212 1818 24 hours24 hours

Bivalirudin monotherapyBivalirudin monotherapy

Heparin + GPIIb/IIIa inhibitorHeparin + GPIIb/IIIa inhibitor

Dangas G. ACC 2009 Scientific Sessions; March 29, 2009; Orlando, FL.


Evento: Genova



1.6%

3.4%

1.5%

1.2%

HR [95%CI] =1.30 [0.54-3.16]P = 0.56

HR [95%CI] =2.11 [1.07,4.17]P = 0.03

1013519

1009 990 969 957 943 863514 497 486 480 474 430

Number at risk600 mg300 mg

Def

/Pro

b S

ten

t T

hro

mb

osi

s (%

)

0

1

2

3

4

5

Time in Days

0 1 30 90 180 270 365

Clopidogrel Loading in Bivalirudin ptsStent Thrombosis 1-Day Landmark Analysis

600mg Clopidogrel

300mg Clopidogrel

Dangas G. ACC 2009 Scientific Sessions; March 29, 2009; Orlando, FL.


Evento: Genova



Comparison of changes in platelet aggregation induced between STEMI patients (n=9) and healthy controls (n=10) after a 600 mg clopidogrel loading dose.Comparison of changes in platelet aggregation induced between STEMI patients (n=9) and healthy controls (n=10) after a 600 mg clopidogrel loading dose.

5 mol/l ADP5 mol/l ADP 20 mol/l ADP20 mol/l ADP

Impaired bioavailability of clopidogrel in STEMI patientsHeestermans A, et al Thrombosis Research 2008;122:776-781

Impaired bioavailability of clopidogrel in STEMI patientsHeestermans A, et al Thrombosis Research 2008;122:776-781


Evento: Genova



Abciximab for primary PCI in STEMIsignificant mortality reduction

-29%

De Luca G, et al. JAMA 2005;293:1759


Evento: Genova



HORIZONS - Outcome in Patients With HORIZONS - Outcome in Patients With Symptom Onset to Hospital ER Admission Symptom Onset to Hospital ER Admission <<2.2 hrs 2.2 hrs

.

-43%

p=0.03

EMEA. Assesement Report For Angiox. Doc. Ref No.:EMEA/724835/2009. Page 10. www.emea.europa.eu

MA

CE

at

30 D

ays

(%)


Evento: Genova



Predictors of no-reflow: the ISAR database

Variable No-reflow

(n =108) Reflow

(n =1032) P value

Left ventricular ejection fraction (%) 48.0 [32.8; 56.9] 50.0 [42.0; 58.0] 0.028 Number of narrowed coronary arteries

0.57

1 39 (36.1) 364 (35.3) 2 29 (26.9) 325 (31.5) 3 40 (37.0) 343 (33.2) Pre-intervention TIMI flow grade <0.001 0 90 (83.3) 564 (54.6) 1 5 (4.6) 109 (10.6) 2 10 (9.3) 189 (18.3) 3 3 (2.8) 170 (16.5) Vessel size (mm) 3.02 [2.65; 3.34] 2.93 [2.58; 3.25] 0.28 Type of intervention 0.96 Stenting 88 (81.5) 843 (81.7) Balloon angioplasty 20 (18.5) 189 (18.3) Pre-procedural abciximab therapy 84 (77.8) 800 (77.5) 0.95

Data are median [25th; 75th %] or number of patients (%)

Ndrepepa J et al. Circ Cardiovasc Interv. 2010;3-27-33


Evento: Genova




Evento: Genova



Troponins elevated or not

ACS without persistent ST-segment elevation


Evento: Genova



Patients judged to be at high risk forPatients judged to be at high risk forprogression to MI or deathprogression to MI or death

Patients with recurrent ischemiaPatients with recurrent ischemiaRecurrent chest painRecurrent chest pain

Dynamic ST-segment changesDynamic ST-segment changes((ST-segment depression or transient ST-segment depression or transient

ST segment elevation)ST segment elevation)

Early post infarction unstable Early post infarction unstable anginaangina

Elevated troponin levelsElevated troponin levelsDiabetesDiabetes

Hemodynamic instabilityHemodynamic instabilityMajor arrhythmias Major arrhythmias (VF, VT)(VF, VT)

Patients with recurrent ischemiaPatients with recurrent ischemiaRecurrent chest painRecurrent chest pain

Dynamic ST-segment changesDynamic ST-segment changes((ST-segment depression or transient ST-segment depression or transient

ST segment elevation)ST segment elevation)

Early post infarction unstable Early post infarction unstable anginaangina

Elevated troponin levelsElevated troponin levelsDiabetesDiabetes

Hemodynamic instabilityHemodynamic instabilityMajor arrhythmias Major arrhythmias (VF, VT)(VF, VT)

Introduction ofGpIIB/IIIA blocker

andCoronary angiography

ESC NSTEACS GUIDELINES YEAR 2002ESC NSTEACS GUIDELINES YEAR 2002


Evento: Genova



GP IIb-IIIa Blockade Before and After PCI: CAPTURE, PURSUIT, PRISM-PLUS

0%

2%

4%

6%

8%

10%

PCI

N=2754 P=0.001

N=12,296P=0.001

+24 h +48 h +72 h +24 h +48 h

Boersma E, et al. Lancet. 2002;359:189-198.

4.3%

2.9%

8.0%

4.9%

Dea

th o

r M

I

Before PCI Post-PCI

Placebo

GP IIb-IIIa inhibitor

0

-33% -39%


Evento: Genova



Impact of early intervention in HR ptsWith NSTEACS: the TIMACS study

Mehta SR, NEJM 2009;360:2165-75

30% of the ptsGRS >140)

Risk of Death, MI or stroke


Evento: Genova



<24h >24-48h >48-72h >72h

% p

ts u

nder

goin

g an

giog

raph

y 100-

80-

60-

40-

20-

0-11 11 15

6260

2010 10

Hub hosp (N=165)

Spoke hosp (N=222)

Time to angiography among NSTEACS ptsIn hub and spoke hospitals of the Reggio Emilia province

Savonitto S et al. GIC 2012;13:157-68


Evento: Genova



CV

D/M

I/S

tro

ke

Time From Randomization

0.5 0.4

0%

4%

5%

24 hr 48 hr 72 hr 0-7 Days

PlaceboN=6303ClopidogrelN=6259

1%

1.11.4

0.91.2

3%

2%

2.52.1

RR=0.80p=NS

RR=0.81p=NS

RR=0.85p=NS

RR=0.82p=NS

CURE: Early Impact of Clopidogrel in UA/NSTEMI

Yusuf S. Circulation 2003;107:968


Evento: Genova



Clopidogrel Pretreatment: Events in UA/NSTEMI Before Cardiac Catheterization

n = 206 n = 68

PCI-CURE (Median time to Catheterization = 10 Days)

n = 159 n = 47

PlaceboClopidogrel

RR=0.6895% CI (0.47-0.99)

p=0.04

RR=0.76 95%CI (0.62-0.93)

p=0.008

% P

atie

nts

MI or Refractory Ischemia

MI

Mehta SR et al. Lancet 2001;358:527-533


Evento: Genova



van der Heijden et al. JACC 2004; 44:20

Clopidogrel Pre-Treatment and Myocardial Damage After Elective Stenting

3,3 3,26,3 7,4

17,220,4

43,3

51,1

0

10

20

30

40

50

60

%

CK-MB > 16 (6-8 h) CK-MB > 16 (16-24 h) Troponin>0.2 (6-8h) Troponin>0.2 (16-24h)

No Pre-TreatmentClopidogrel Pre-Treatment (3 days)

N = 203


Evento: Genova



28.1

7166.7

0

20

40

60

80

100

Pre-PCI Post-PCI

TM

PG

0/1

(%

)T

MP

G 0

/1 (

%)

6.2

35.5

20

0

10

20

30

40

50

Tissue Level Perfusion by TMPG pre and post-PCI

UpstreamUpstreamTirofibanTirofiban

HBDTirofiban

Abciximab

p=0.015

TM

PG

0/1

(%

)T

MP

G 0

/1 (

%)

UpstreamUpstreamTirofibanTirofiban

HBDHBDTirofibanTirofiban

AbciximabAbciximab

P= 0.0009

Bolognese L et. JACC 2006;47:522


Evento: Genova



Giugliano RP. N Engl J Med 2009;360:2176-90Giugliano RP. N Engl J Med 2009;360:2176-90


Evento: Genova



What Early ACS really showed?

1. The trial compared early vs delayed eptifibatide, rather

than GPIIB/IIIa and control

2. Only 59% of the pts underwent PCI, and drug therapy was

strikingly different between North America and Europe (pre-

PCI clopid 50% NA, 85% Europe)

1. The trial compared early vs delayed eptifibatide, rather

than GPIIB/IIIa and control

2. Only 59% of the pts underwent PCI, and drug therapy was

strikingly different between North America and Europe (pre-

PCI clopid 50% NA, 85% Europe)



Evento: Genova




What Early ACS really showed?

PE: D+MI+ recurrent ischemia requiring urgent revasc, or thrombotic bailout at 96 hPE: D+MI+ recurrent ischemia requiring urgent revasc, or thrombotic bailout at 96 h

SE: D+MI at 30 daysSE: D+MI at 30 days


Evento: Genova



death or MI 11.2 vs 12.3 0.89 (0.79–1.01)

0.079

Death 2.8 vs 2.6 1.10 (0.86–1.41) 0.46

Myocardial infarction 9.5 vs 10.6 0.88 (0.77–1.01)

0.073

Death, MI, RI req urg revasc 12.5 vs 13.8 0.89 (0.79–1.01)

0.065

RI req urg revasc 2.4 vs 2.9 0.80 (0.62–1.03) 0.083

death or MI 11.2 vs 12.3 0.89 (0.79–1.01)

0.079

Death 2.8 vs 2.6 1.10 (0.86–1.41) 0.46

Myocardial infarction 9.5 vs 10.6 0.88 (0.77–1.01)

0.073

Death, MI, RI req urg revasc 12.5 vs 13.8 0.89 (0.79–1.01)

0.065

RI req urg revasc 2.4 vs 2.9 0.80 (0.62–1.03) 0.083

30-day Primary Efficacy Resultsafter shrinking the power

Delayed Eptifibatide

(n=4684)

Early Eptifibatide

(n=4722)

OR (95% CI) P



Evento: Genova



30-day Death or MI

0.7 0.80.5 0.6 0.9 1 2

Overall 11.2 12.3

Men 11.4 12.0

Women 10.7 13.0

Age < 75 yr 10.2 11.6

14.0 14.6

Troponin positive 11.6 13.0

Troponin negative 8.1 8.4

Diabetes 11.7 13.8

No Diabetes 10.9 11.7

Early clopidogrel intended 10.3 12.0

No early clopidogrel intended 13.7 13.4

Baseline Characteristic

Early Eptifibatide Better Delayed Provisional Eptifibatide Better

Age > 75 yr

Odds Ratio for UpstreamEptifibatide (95% CI)

Routine Early Eptifibatide, %

Delayed Provisional

Eptifibatide, %



Evento: Genova



Medical Only (N=1706)Total Events = 71

CABG (N=251)Pre-CABG Events = 22Post CABG Events = 46

PCI (N=2723)Pre-PCI Events = 87

Post-PCI Events = 243

Medical Only (N=1784)Total Events = 71

CABG (N=268)Pre-CABG Events = 33Post-CABG Events = 52

PCI (N=2666)Pre-PCI Events = 82

Post-PCI Events = 201

Total Events on Medical Treatment = 71 + 82 +33 Total Events on Medical Treatment = 71 + 87 +

22

Group Events Risk Rate Group Events Risk Rate

Medical 186 4718 4.1% Medical 180 4680 4.0%

Post PCI 201 2584 8.0% Post PCI 243 2636 10.5%

Post CABG 52 235 23.4% Post CABG 46 229 20.6%

Medical Only N=3490 PCI N=5389

CABG N=519

Medical Only N=3490 PCI N=5389

CABG N=519

Strategy During First 96 HoursStrategy During First 96 Hours

RandomizationN=9406

Delayed Provisional Eptifibatide (N=4680)Total Events = 469

Early Eptifibatide (N=4718)Total Events = 439

-24%-24%


Evento: Genova



Impact of abciximab on top of ASA and clopidogrel

Death or MI at 30 days

Kastrati A, NEJM 2004, JAMA 2006

20-20-

18-18-

16-16-

14-14-

12-12-

10-10-

8-8-

6-6-

4-4-

2-2-

0-0-Placebo AbciximabPlacebo Abciximab Placebo AbciximabPlacebo Abciximab Placebo AbciximabPlacebo Abciximab

4.04.04.04.0 4.04.04.04.0 4.64.64.64.6 4.64.64.64.6

13.113.113.113.1

18.318.318.318.3

ISAR REACT 1ISAR REACT 1 ISAR REACT 2ISAR REACT 2TnT negativeTnT negative

ISAR REACT 2ISAR REACT 2TnT positiveTnT positive

P=0.98P=0.98P=0.91P=0.91

-28%-28%P=0.02P=0.02


Evento: Genova




Bleeding events

Early eptifibatide

N=4722

Early eptifibatide

N=4722

Delayed eptifibatide

N=4684

Delayed eptifibatide

N=4684


Evento: Genova



Contemporary recommendations on Antiplatelet therapy in NSTEACS PCI


Evento: Genova



ACC/AHA NSTEACS GuidelinesACC/AHA NSTEACS Guidelines


Evento: Genova



How would you treat this patient?


Evento: Genova



Probability of 30-D death by sum of ST depressionon the admission ECG: the GUSTO IIb ECG corelab

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0 5 10 15 20 25 30 35 40 45

sum of ST depression (mm)

Pro

bab

ilit

y o

f 30

-day

dea

th

Probability of death

95% confidence limits

Savonitto S et al: Eur Heart J 2005;26: 2106

1+2 Q(n=2493)

3 Q(n=1366)

4 Q(n=1333)

50-

40-

30-

20-

10-

0-

% 3-vessel disease

% LM disease

Incidence of 3VD and LMCA diseaseby quartiles of ST depression


Evento: Genova



The Lipsia NSTEACS randomised trial

Thiele H. Eur Heart J 2012;33:2035


Evento: Genova



ACUITY: Invasive Management

UFH/Enoxaparin + GP IIb/IIIa(N=4,603)

Bivalirudin + GP IIb/IIIa

(N=4,604)

Bivalirudin alone

(N=4,612)

Angiography 99.2% 98.8% 98.9%

Adm. to angio (h) 19.7 (7.0-29.3)† 19.5 (7.0-28.2)† 19.8 (7.3-29.0)†

Drug* to angio/interv (h) 5.6 (1.6-22.5)† 5.0 (1.4-21.4)† 5.2 (1.5-22.5)†

Actual procedure

PCI 55.6% 56.7% 56.8%

CABG 11.9% 10.8% 10.6%

Medical therapy 32.4% 32.5% 32.6%

†median (IQR)

Stone GW, Presented at 2006 ACC Meeting.Available at www.Clinicaltrialsresults.orgStone GW, Presented at 2006 ACC Meeting.Available at www.Clinicaltrialsresults.org


Evento: Genova



Berger JS. JACC 2008;52:1693

Predictors of reoperation in ACS patients undergoing CABG

Clopidogrel <5 days

4.601 1.454-14.554 0.009

Pre-op aspirin

0.616 0.109-3.483 0.584

Pre-op

GPI

1.825 0.504-6.613 0.360

Prior

CABG

5.299 1.050-26.734 0.043

Odds ratioOdds ratio 95% CI95% CI P-valueP-value


Evento: Genova



Outcome300mg Loading Dose

(n=148)>600mg Loading Dose

(n=48) P

Major bleeding, 70 (47%) 35 (73%) 0.002

Re-operation for bleeding,

7 (5%) 6 (12%) 0.09

Tamponade 4 (3%) 2 (4%) 0.64

Mean 24h Chest tube loss

391 ± 251 mL 536 ± 354 mL 0.01

Post-operative MI 8 (5%) 5 (11%) 0.31

Post-operative CVA 6 (4%) 1 (2%) 0.34

LOS in surgical intensive care, days

4.3 ± 4.1 5.0 ± 3.1 0.0001

In-hospital death 7 (5%) 1 (2%) 0.68

Clopidogrel loading dose and bleeding in NSTEACS patients undergoing urgent CABG

Cruden NL. Am Heart J 2011;161:404


Evento: Genova




Evento: Genova



Transfusions from time of CABG

Any transfusion

0.88 (0.67, 1.16)Platelets

1.03 (0.88, 1.20)PRBC or whole blood*

0.83

Transfusions within 7 days post-CABG

0.98 (0.85, 1.14)

Fresh frozen plasma 1.05 (0.84, 1.31)

0.69

0.37

0.67

Transfusions post CABG-related bleeding

1.25 (0.70, 2.23)>5 units whole blood/PRBC (2 days)

1.12 (0.83, 1.53)>4 units blood

Chest tube output >2L (24 hours)

1.24 (0.61, 2.52)

0.45

0.49

0.62

Ticagrelor better Clopidogrel better

0.5 1.0 2.00.2*Median (range) units transfused within 7 days post-CABG:

tic 3.0 (2.0–4.0) vs. clop 3.0 (2.0–4.0); p=0.86

p-valueHazard/Odds Ratio (95% CI)Ticagrelor(n=632)

Clopidogrel(n=629)

15.3 17.3

52.7 51.2

55.2 55.8

25.2 24.0

4.9 4.0

17.9 16.2

3.3 2.7

Characteristic

Held C, JACC 2011;57:672


Evento: Genova



Time from CABG to CV death

0 1 2 3 4 5 6 7 8 9 10 11 12

8

7

6

5

4

3

2

1

0

Months from CABG procedure

HR: 0.52 (95% CI = 0.32–0.85), p<0.01

7.9

4.1

Clopidogrel (n=629)

Ticagrelor (n=629)

K-M

est

imat

ed r

ate

(%)

Held C, JACC 2011;57:672


Evento: Genova



Smith PK. JACC 2012; epub ahead of print 24 May 2012

Bleeding and mortality after isolated CABGClopidogrel vs prasugrel

mean 12-h chest tube blood loss (655 + 580 ml vs. 503 + 378 ml; p 0.050)


Evento: Genova



Event rates for patient undergoing CABG in PURSUIT (< 72 h of GP IIb/IIIa discontinuation)

Marso SP et al; Circulation 2000;102:2952-8

15%15%

35%35%

00 3030 6060 9090 120120 150150 180180

days from randomizationdays from randomization

33.633.6%%

23.8%23.8%

RRR RRR 30%30%

p = p = 0.0020.002

25%25%

cum

ulat

ive

inci

denc

e (%

)cu

mul

ativ

e in

cide

nce

(%)

placeboplacebo

eptifibatideeptifibatide


Evento: Genova



Caso clinico 13 settembre 2012Caso clinico 13 settembre 2012

•Uomo di 72 anni senza precedenti cardiovascolari né rilevanti fattori di rischio.•Maratoneta amatoriale fino a un anno fa.

• Il 12 settembre esegue nel nostro Ospedale intervento di litotrissia endovescicalee vaporizzazione prostatica “green light laser” per calcolosi vescicale e IPB ostruente

• Lo stesso pomeriggio, lieve epigastralgia durata 15 minuti, a risoluzione spontanea

• Visita cardiologica (sintomatologia aspecifica) + ECG – richiesti enzimi cardiaci

• La mattina successiva, CKMB 75 ng/ml• Evoluzione ECG





• La mattina successiva, CKMB 75 ng/ml• Evoluzione ECG


Evento: Genova




Evento: Genova



Caso clinico 13 settembre 2012Caso clinico 13 settembre 2012





• La mattina successiva, CKMB 75 ng/ml• Evoluzione ECG • Flectadol 500 mg – Trasferimento in UTIC• Eseguita coronarografia: occlusione trombotica coronaria destra distale• Eseguita tromboaspirazione + POBA con ottimo risultato angiografico

• Tirofiban 24 ore post-procedura in vista di stenting 17 Settembre.





• La mattina successiva, CKMB 75 ng/ml• Evoluzione ECG • Flectadol 500 mg – Trasferimento in UTIC• Eseguita coronarografia: occlusione trombotica coronaria destra distale• Eseguita tromboaspirazione + POBA con ottimo risultato angiografico

• Tirofiban 24 ore post-procedura in vista di stenting 17 Settembre.

Data: 9 Novembre 2012 Evento: Genova Titolo: added value of GPIIb/IIIa RB in ACS Autore: Stefano...

Documents

Transcript of Data: 9 Novembre 2012 Evento: Genova Titolo: added value of GPIIb/IIIa RB in ACS Autore: Stefano...