ST

YKSELMEL MYOKARD
NFARKTSNDE KORONER
TROMBSLE MCADELE
Do.Dr.Erturul Okuyan

28 yanda, Bayan Hasta

Akut nferior MI tansyla ve 4 saatlik ar
yaknmasyla bavurdu
Youn sigara iicisi
Hiperlipidemisi mevcut
Aile yks poziHf

 PPKG srasnda distal embolizasyon %15 orannda

gzlenebilmektedir ve ileme bal komplikasyonlarn sk bir
nedenidir.
Distal embolizasyon oluanlarda 5 yllk mortalite %44 iken
olumayanlarda %9dur
Distal embolizasyondan birincil olarak sorumlu trombs
younluudur

Burzotta F et al. Eur Heart J 2009;30:2193-2203

DSTAL EMBOL
Mekanik olarak mikrovaskler yata Ikayarak
miyokardn devam eden iskemik nekrozuna yol
aar.
Lokal olarak in-situ platelet adhezyonunu ve
trombosisi uyararak doku perfzyonunun
bozulmasna ve no-reow fenomenine yol
aabilir.
Mikrovaskler spazm ve lokal enamatuar sreci
uyararak daha fazla miyokard nekrozuna sebep
olabilir

Mikrovaskler obstrksiyon

SubopHmal reperfzyon
Artm enfarkt alan
Azalm ventrikl fonksiyonu
5-yllk mortalitede 5 kat arI

Akut reperfzyon parametreleri

Thrombolysis in myocardial infarcHon(TIMI)
ow
Myocardial Blush Grade(MBG)
lem sonras EKG de ST segment rezolsyonu
LER TETKKLER
-Myocardial contrast echo
-Cardiovascular MRI(Gadolinium)

STENT TROMBOZU
Angiographic Stent Thrombosis A[er RouHne Use of Drug-EluHng Stents in
ST-Segment ElevaHon Myocardial InfarcHon: The Importance of Thrombus
Burden
Georgios Sianos, MD, PhD, , Michail I. Papafaklis, MD, Joost Daemen, MD,
Soa Vaina, MD, Carlos A. van Mieghem, MD, Ron T. van Domburg, PhD,
Lampros K. Michalis, MD, MRCP, Patrick W. Serruys, MD, PhD, FACC
Show more
doi:10.1016/j.jacc.2007.04.059
Journal of the American College of Cardiology

Fazla trombs yk olan damarlarda primer PCI

sonras stent trombozu oranlar anlaml olarak
artmaktadr( 8.2% vs 1.3% p<0.001)

TIMI TROMBS SINIFLAMASI

TIMI
TROMBS 0

TROMBS YOK

TIMI
TROMBS OLMA HTMAL VAR
TROMBS 1
TIMI
TROMBS VAR EN BYK UZUNLUU
TROMBS 2 DAMAR APININ <1/2
TIMI
TROMBS VAR EN BYK UZUNLUU
TROMBS 3 DAMAR APININ >1/2 FAKAT <2
TIMI
TROMBS VAR EN BYK UZUNLUU
TROMBS 4 DAMAR APININ >2
TIMI
TOTAL TIKALI
TROMBS 5

Glimm et al. Circulation 2001;21:2550

Primer PCIda Koroner trombsn

distal embolizasyonunu nleme
stratejileri
1-Trombs rezolsyonu iin Farmakolojik
yaklamlar
2-AdjuncHve mekanik cihazlar(Trombs
aspiarasyonu ve Embolik proteksiyon cihazlar)

Gp2b/3a RESEPTR ANTAGONSTLER

Abciximab

Eftifibatide

Tirofiban

Hzl affinite
Yava ayrlm
Yarmasz
inhibisyon

Yava affinite
Hzl ayrlm
Yarmal
inhibisyon

Yava affinite
Hzl ayrlm
Yarmal
inhibisyon

Etkinliin balangc 10-26 dakika

90-150 dakika

90-150 dakika

Vcttan atlm

12-24 saat

2-4 saat

2-4 saat

Atlm yolu

Plasma
proteazlar

Bbrek

Bbrek(%30-60)
Karacier (%40-70)

Dier

-3 integrin
(vitronectin),
MAC-1 reseptr
inhibisyonu

Reseptr affinitesi

RANDOMIZED STUDIES
1590 paXents
PopulaXon
Access
IC
Site

Study

GPI

ICE, 2010

E[ibaHde

ACS
(26%STEMI)

CICERO, 2010

Abciximab

STEMI

Iverson et al ,2011

Abciximab

STEMI

Dominguez et al,
2009

Abciximab

STEMI

Wu et al, 2008

Tiroban

ACS
(63%STEMI)

Thiele et al, 2008

Abciximab

Yang et al, 2007

Femoral

IV

IC bolus/18-h IV inf.

IV bolus/18-h IV inf.

IC bolus a[er
thrombectomy

IV bolus a[er
thrombectomy

IC bolus/12-h IV inf.

IV bolus/12-h IV inf.

IC bolus a[er
thrombectomy/12-h IV
inf.

IV bolus a[er
thrombectomy/12-h IV inf.

IC bolus/36-h IV inf.

IV bolus/36-h IV inf.

STEMI

IC bolus /12-h IV inf.

IV bolus/12-h IV inf.

Tiroban

STEMI

IC bolus/36-h IV inf.

IV bolus/36-h IV inf.

Bellandi et al, 2004

Abciximab

STEMI

IC bolus/12-h IV inf.

IV bolus/12-h IV inf.

LIPSIA-STEMI 2010

Abciximab

STEMI

IC bolus/12-h IV inf

IV bolus/12-h IV inf

EASY-MI, 2010

Abciximab

STEMI

Transradial

IC bolus/12-h IV inf

IV bolus/12-h IV inf

Galache Osuna et al,

2006

Abciximab

ACS
(41%STEMI)

Radial or femoral

IC bolus/12-h IV inf

IV bolus/12-h IV inf

Femoral

Femoral

Friedland S et al. Am J Cardiol 2011;108:1244-1251

 What is The Reason to Prefer Local

Coronary Infusion of IIb/IIIa
Inhibitors ??

 Her bir trombosit yzeyinde 60 000 to 80 000 GP IIb/IIIa receptr

bulunmaktadr. Tedavi, bu reseptrlerin en az %80ini bloke etmeyi
amalamaktadr.
IC GP IIbIIIa receptor inhibitor uygulanmas ile daha fazla lokal
konsantrasyon salanmakta ve platelet GP IIb/IIIa receptor
occupancy artmaktadr.
Ayrca yksek lokal konsantrasyonlar, trombs disagregasyonu
salayabilmektedir.

 Abciximab, yksek lokal konsantrasyonlarda potent anH-

enamatuar etki gsterir. Bu etki i.v. Uygulamada
gsterilememiHr.
IC uygulama ile , post-PCI i.v. Uygulama gereksinimi ortadan
kalkabilir ve bylece sistemik ila konsantrasyonlar minimize
edilerek kanama olaylar azalabilir.
Abciximab bolus uygulamas, total dozun 75% ine karlk gelir..
Pharmacological data , single bolus (0.25 mg/kg) abciximab ile
>80% of platelet aggregaHon inhibisyonu salanabildii ve bu
etkinin saatlerce srdn gstermiHr.
Domiguez A et al. Atherosclerosis 2009;206:523-27

GPIIb/IIIa IC versus IV
TIMI 3 FLOW AFTER PCI
Study

RR
(95% CI)

% Weight

ICE

1.07 (0.89-1.28)

8.66

CICERO

1.03 (0.97-1.10)

34.90

Iversen

1.10(0.96-1.24)

17.43

Dominquez-Rodriquez

1.29 (0.96-1.76)

3.27

Wu

1.22 (1.01-1.48)

7.96

Thiele

0.98(0.86-1.12)

14.25

Yang

1.27(0.98-1.64)

4.60

EASY-AMI

1.15 (0.96-1.37)

8.92

Overall (I-squared=20.1%,p=0.270)

1.08 (1.02-1.15)

100.0

0.5

IV better

1.5

IC better

Friedland S et al. Am J Cardiol 2011;108:1244-1251

GPIIb/IIIa IC versus IV
SHORT-TERM TVR
Study

RR
(95% CI)

% Weight

CICERO

0.87 (0.36-2.12)

32.91

Iversen

0.40(0.17-0.95)

54.08

Wu

0.33 (0.01-7.86)

4.91

0.20(0.01-4.10)

8.11

0.54 (0.30-0.96)

100.0

Thiele

Overall (I-squared=0.0%,p=0.552)

0.5

IC better

1.5

IV better

Friedland S et al. Am J Cardiol 2011;108:1244-1251

GPIIb/IIIa IC versus IV
30 DAY MORTALITY
Study

RR
(95% CI)

% Weight

CICERO

0.69 (0.22-2.16)

28.34

Iversen

0.20 (0.04-0.93)

37.42

Wu

0.49(0.05-5.27)

8.05

Thiele

0.67(0.11-3.98)

11.97

Yang

0.19 (0.01-3.71)

10.33

Bellandi

1.05(0.07-15.70)

3.90

Overall( I-squared=0.0%,p=0.777)

0.45 (0.23-0.90)

100.0

0.5

IC better

1.5

IV better

Friedland S et al. Am J Cardiol 2011;108:1244-1251

GPIIb/IIIa IC versus IV
SHORT-TERM BLEDNG EVENTS
Study

RR
(95% CI)

% Weight

CICERO

1.11 (0.68-1.81)

35.69

Iversen

0.69 (0.41-1.17)

38.01

Dominguez-Rodriquez

0.67(0.12-3.65)

3.91

Wu

0.76(0.31-1.91)

11.82

Thiele

0.80(0.22-2.87)

6.51

Yang

2.17(0.63-7.51)

4.05

Overall( I-squared=0.0%,p=0.562)

0.92(0.68-0.1.24)

100.0

0.5

IC better

1.5

IV better

Friedland S et al. Am J Cardiol 2011;108:1244-1251

Intracoronary Versus Intravenous Administration of

Abciximab in Patients With ST-Segment Elevation
Myocardial Infarction Undergoing Primary
Percutaneous Coronary Intervention With Thrombus
Aspiration
The Comparison of Intracoronary Versus Intravenous Abciximab
Administration During Emergency Reperfusion of ST- Segment
Elevation Myocardial Infarction
(CICERO) trial

ENZYMATIC INFARCT SIZE

Intracoronary
(n=126)

Intravenous
(n=122)

Peak CK, U/L

1214

1746

0.008

Peak CK-MB, U/L

154

232

0.003

Peak cTnT, g/L

3.03

4.36

0.008

30 % Smaller in the IC group

Gu Y L et al. Circulation 2010;122:2709-2717

Clinical Outcome at 30 Days

Intracoronary
(n=271), n(%)

Intravenous
(n=263)

Mortality

5 (1.8)

7 (2.7)

0.524

Cardiac mortality

4 (1.5)

6 (2.3)

0.492

TVR

9 (3.3)

10 (3.8)

0.764

ReinfarcXon

3 (1.1)

4 (1.5)

0.721

In-stent thrombosis

1 (0.4)

3 (1.1)

0.366

MACEs

15 (5.5)

16 (6.1)

0.786

Gu Y L et al. Circulation 2010;122:2709-2717

Intracoronary Compared with Intravenous Bolus

Abciximab Application
During Primary
Percutaneous Coronary Intervention
The Abciximab Intracoronary versus intravenously Drug
Application in ST-Elevation Myocardial Infarction
(AIDA STEMI) trial
Holger Thiele, MD;
Jochen Whrle, MD; Rainer Hambrecht, MD; Harald Rittger, MD; Ralf Birkemeyer, MD;
Bernward Lauer, MD; Petra Neuhaus, PhD; Oana Brosteanu, PhD; Peter Sick, MD; Marcus Wiemer, MD;
Sebastian Kerber, MD; Ingo Eitel, MD; Klaus Kleinertz, MD; Gerhard Schuler, MD
on behalf of the AIDA STEMI Investigators

ST-Segment-Resolution

Frequency

IV Abciximab

p=0.37
IC Abciximab

Early ST-Segment Resolution (%)

Conclusions
This randomized, multi-center, large-scale trial involving
more than 2000 STEMI patients undergoing primary PCI
showed that IC abciximab bolus administration is safe.
The IC bolus administration of abciximab does not add a
benefit in comparison to the standard IV bolus with respect
to the combined primary study endpoint consisting of death,
reinfarction, or new congestive heart failure within 90 days.
The IC route might be related to reduced rates of new
congestive heart failure.

IC bolus doses of GPIIb/IIIa inhibitors

Bolus Dose

Infusion dose

Abciximab

0.25mg/kg

0.125g/kg/min

E[ibaHde

180 g/kg

2g/kg/min

Tiroban

10 g/kg

0.15g/kg/min

Guiding catheters without side holes must be prefer to

administer i.c. GPIIb/IIIa inhibitors

Friedland S et al. Am J Cardiol 2011;108:1244-1251

MORE BENEFIT FROM IC GpIIb/IIIa

High thrombus burden; aspiraHon
thrombectomy (-)
Symptom duraHon is long (>4 hour)
High risk paHents (type B2/C lesions,
dissecHon,no-reow)

TROMBEKTOM LE BRLKTE
YAPILIRSA ?

ATTEMPT VER TABANI

Burzotta F et al. Eur Heart J 2009;30:2193-2203

INFUSE AMI TRIAL

INFUSE AMI TRIAL: Intracoronary bolus dose
of abciximab delivered with a dedicated
infusion catheter (Clear-Way) versus no bolus
with or without thrombus aspiraHon in
paHents treated with bivalirudin

INFUSE-AMI is tesHng the hypothesis that the intracoronary administraHon of an abciximab

bolus with or without thrombus aspiraHon before stent implantaHon compared to no
infusion with or without thrombus aspiraHon reduces infarct size among paHents undergoing
primary PCI for anterior STEMI who are treated with bivalirudin.

From: Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial
Infarction: The INFUSE-AMI Randomized Trial
JAMA. 2012;307(17):1817-1826. doi:10.1001/jama.2012.421

Figure Legend:
More than 1 reason for study exclusion were present in some patients who were not eligible for randomization. Cardiac magnetic
resonance imaging (cMRI) at 30 days was not performed in 70 enrolled patients for the following reasons: patient refusal or
withdrawn consent for cMRI (n=27); patient inability to complete the cMRI (most commonly for claustrophobia) (n=15); death
before the 30-day cMRI (n=13); too ill (n=4); patient forgot (n=4); contrast contraindication (n=2); other (n=5). In addition,
despite being performed, the cMRI study was
not evaluable
for the primary
point of infarct size in 29 patients because of
Copyright
2014 American
Medical end
Association.
Date
of
download:
12/8/2014
technical issues in image acquisition, including incorrectAll
image
inadequate inversion recovery time, excessive
rightssequencing,
reserved.
breathing artifact, and missing slices. CABG denotes coronary artery bypass graft; GPI, glycoprotein IIb/IIIa inhibitor; IC,

INFUSE AMI -SONU

In paHents with large anterior STEMI
presenHng early a[er symptom onset and
undergoing primary PCI with bivalirudin
anHcoagulaHon, infarct size at 30 days was
signicantly reduced by bolus intracoronary
abciximab delivered to the infarct lesion site
but not by manual aspiraHon thrombectomy.


STEMI IV Antiplatelet
Therapy:
Recommendations

I IIa IIb III

In patients undergoing primary PCI treated with UFH, it is
a GP IIb/IIIa inhibitor (abciximab, doublereasonable to administer
bolus eptifibatide, or high-bolus dose tirofiban), whether or not
patients were pretreated with clopidogrel. (For GP IIb/IIIa inhibitor
administration in patients not pretreated with clopidogrel, Level of
Evidence: A; for GP IIb/IIIa inhibitor administration in patients
pretreated with clopidogrel, Level of Evidence: C)

I IIa IIb III

In patients undergoing primary PCI with abciximab, it may be
reasonable to administer intracoronary abciximab.(Level of
Evidence: B)

These agents might provide more benefit in selective use, such as in patients with large anterior MI and/or
large thrombus burden (TIMI thrombus grade >3)
Levine et al. J Am Coll Cardiol 2011;58:917-24

Primer PKG'de adjuvant

mekanik yntemler (Manuel Mekanik Aspirasyon, DistalProksimal Proteksiyon):
Kime, nasl?

Primer PKG'de adjuvant mekanik

yntemler ne salyor??
Trombs younluunu azaltarak;
-Distal embolizasyonu azaltyor,
-Direkt stentlemeyi salyor,
- Vazokonstriksyonu azaltyor,
-Damar apnn daha iyi belirlenmesini salayp
malappozisyon gelimesini engelliyor,
-Gerek aterosklerotik darln gzkmesini salayarak
bu darln medikal tedavi ile stabilize olup
olamayacan gsterebiliyor

De Luca G et al. Int J of Cardiol BASKIDA

PPKG SIRASINDA KULLANILAN ADJUVANT MEKANK

YNTEMLER

Manuel Aspirasyon
Mekanik Aspirasyon
Distal-Proksimal Proteksiyon

Distal embolizasyon zaman

Napadono ,2005

ASPRASYON CHAZLARI
MANUEL

MEKANK

EXPORT

ANGIOJET

DIVER CE

X-SIZER

PRONTO

THROMCAT

QUICKCAT

RINSPIRATOR

THROMBUSTER
RESCUE
TVAC

PROTEKSYON CHAZLARI
DSTAL
FLTRE

BALON TIKAYICI

Angioguard

Guardwire

Filterwire

TriActive

Cardioshield
(Emboshield)

Theron

Spider RX

MoMa

Interceptor

Arteria

PROKSMAL
PROKSS
KERBEROS RINSPIRATOR
PARODI

MANUEL ASPRASYON-30 GN LM
alma

RR
(95% CI)

De Luca ve ark.

0.19(0.01-4.08)

6.59

EXPIRE

0.33 (0.01-8.11)

4.01

EXPORT

0.35(0.01-8.93)

3.78

EXPORT ALIMASI

0.64 (0.15-2.72)

12.55

PIHRATE

0.94 (0.18-4.77)

8.02

REMEDIA

1.00(0.19-5.22)

7.51

VAMPIRE

0.97(0.06-15.66)

2.69

TAPAS

0.52(0.25-1.08)

54.82

TOPLAM(%95 CI)

0.58 (0.34-0.98)

100.0

P=0.04

0.1

0.5

Manual trombektomi
iyi

10

Kontrol iyi
De Luca G et al. Eur Heart J 2008;29:3002-3010

MANUEL ASPRASYON-TIMI 3 AKIM

alma

RR
(95% CI)

DEAR MI

2.28(0.91-5.71)

5.49

De Luca ve ark.

1.73 (0.61-4.88)

4.79

EXPIRE

2.03(1.00-4.11)

9.60

EXPORT

5.49(0.59-50.79)

0.73

EXPORT ALIMASI

1.93 (0.70-5.32)

4.95

PIHRATE

1.42(0.73-3.60)

8.33

VAMPIRE

1.70(0.94-3.05)

15.20

TAPAS

1.29(0.92-1.82)

50.91

TOPLAM(%95 CI)

1.59 (1.26-2.00)

100.0

P<0.0001

0.1

0.5

Kontrol iyi

10

Manual trombektomi
iyi

De Luca G et al. Eur Heart J 2008;29:3002-3010

MANUEL ASPRASYON-MBG 3
alma

RR
(95% CI)

DEAR MI

9.48(4.11-21.85)

2.54

De Luca ve ark.

3.85 (1.22-12.14)

2.06

EXPIRE

5.91(3.08-11.35)

4.84

EXPORT

2.27(0.73-7.07)

2.58

EXPORT ALIMASI

1.63 (0.92-2.90)

11.86

PIHRATE

2.33(1.21-4.48)

7.68

VAMPIRE

3.32(2.07-5.33)

12.55

TAPAS

1.77(1.36-2.29)

55.99

TOPLAM(%95 CI)

2.44(2.04-2.92)

100.0

P<0.00001

0.1

0.5

Kontrol iyi

10

Manual trombektomi
iyi

De Luca G et al. Eur Heart J 2008;29:3002-3010

Trombektomi ve Emboli Koruma Cihazlarnn AM deki

Rol: Randomize almalarn Metaanalizi
Bavry et al. Eur Heart J 2008
30 randomize alma: n=6415
13 manuel aspirasyon %47
5 mekanik aspirasyon %38
12 emboli koruma cihaz %15
<12 st STEMI, TIMI 0/1, grnr trombs
Ortalama izlem 6 ay

ST YKSELMEL M 30 ALIMA 6 AY MORTALTE

6

P=0.05

5.3

2.8

Adjuvant cihaz
Sadece PKG

P=0.018

2.7

4.4

P=0.69

3.1

3.4

0
Manuel Aspirasyon

Mekanik Aspirasyon

Proteksiyon cihaz

Bavry A A et al. Eur Heart J 2008;29:2989-3001

STEMI de Trombektominin Klinik

Etkisi :ATTEMPT

11 alma ,n=2686, izlem median 1 yl, PSN total mortalite

PKG yaplan STEMI hastalarnda trombektomi (zellikle manuel trombektomi) klinik
sonular olumlu etkiler, GpIIbIIIa inh ek yarar salayabilir.

Metaanaliz: de Luca et al.

30 gnlk Mortalite

SONU
PPKG'de adjuvant mekanik yntemler
Manuel aspirasyon cihazlar ile mortalitede bir
azalma,
Mekanik aspirasyon cihazlar ile mortalitede bir
art saptanrken,
Emboli proteksiyon cihazlar ile mortalitede bir
fark saptanmamtr

Trombektominin PPKG sonularna etkisi: Metaanaliz

Mongeon FP, CirculaHon Cardiovascular IntervenHons 2010

21 alma, 4299 hasta (16 alma 3365 hasta manuel trombektomi)

Sonu: Trombektomi reperfzyonu olumlu etkiliyor ama 1 aylk

klinik sonulara etkisiz

Thrombus Aspiration during Primary

Percutaneous Coronary Intervention
TAPAS Trial
Tone Svilaas, M.D., Pieter J. Vlaar, M.Sc., Iwan C. van der Horst, M.D., Ph.D., Gilles
F.H. Diercks, M.D., Ph.D., Bart J.G.L. de Smet, M.D., Ph.D., Ad F.M. van den Heuvel,
M.D., Ph.D., Rutger L. Anthonio, M.D., Ph.D., Gillian A. Jessurun, M.D., Ph.D., EngShiong Tan, M.D., Albert J.H. Suurmeijer, M.D., Ph.D., and Felix Zijlstra, M.D., Ph.D.

N Engl J Med 358(6):557-567

February 7, 2008

TAPAS TRIAL
Manuel Aspirasyon
N=1071, tek merkez, randomize,6F Export
Aspirasyon+ direkt stent vs stent
MBG 0-1 %17,1 vs %26.3 ,P<0.00
Tam ST segment dzelmesi %56.6 vs 44.2, p<0.01
lm insidansnda azalma %2.1 vs %4, RR 0.52
%95CI 0,26- 1.07;p=0.07
Svilaas TL, N Eng J Med 2008

STEMI de trombs aspirasyonu bazal klinik ve anjiyograk zelliklerden

bamsz olarak konvansiyonel PKG ye gre daha iyi reperfzyon ve klinik
sonu salar.

One year follow up

All cause mortality: 38% reduction

Cardiac death: 46% reduction
Cardiac death/MI: 43% reduction

Vlaar et al. Lancet 2008;371:1915-20..

PIHRATE: PPKG de Trombs Aspirasyonu +Direkt Stent

Dudek et al. Am Heart J 2010;160:966-72

EXPIRA
Erken sonu:

2 yllk sonular:

Sardella G. American Heart AssociaXon 2009 ScienXc Sessions; November 14, 2009;
Orlando, FL.

Kime yapalm? Erken gelen vs ge gelen?

Hangi hastada yararl?

Thrombus AspiraXon in ST- ElevaXon

myocardial infarcXon
in Scandinavia (TASTE trial)


Main results at 30 days
Ole Frbert, MD, PhD - on behalf of the TASTE invesHgators
Departement of Cardiology
rebro University Hospital
Sweden

TASTE ALIMASI
TASTE (Thrombus aspiraHon during ST-
segment elevaHon myocardial
infarcHon) almas, STEMIde trombs
aspirasyonu ile ilgili en nemli almadr .
TASTE almasna 7244 hasta alnm, 3621i
trombs aspirasyonu koluna, 3623 kontrol
grubuna randomize edilmiHr.

TASTE and previous studies

TASTE
TASTE
TAPAS
JETSTENT
AIMI
INFUSE-AMI
VAMPIRE
PREPARE
Chevalier
Kalto[
MUSTELA
X AMINE ST
PIHRATE
EXPIRA
DEAR-MI
Liistro
0

1000

2000

3000

4000
Number of paXents

5000

6000

7000

8000

TASTE -30. GN SONULAR

30. gn sonunda lm oranlar asndan 2
grup arasnda fark yok.

All-cause mortality at 30 days

HR 0.94 (0.72 - 1.22), P=0.63

Per protocol analysis based on

actual treatment:
HR 0.88 (0.66 - 1.17), P=0.38

ReinfarcXon at 30 days

HR 0.61 (0.34 - 1.07), P=0.09

Per protocol analysis based on

actual treatment:
HR 0.67 (0.36 - 1.20), P=0.19

TASTE-1.YIL SONULARI
Lagerqvist B1, Frbert O, Olivecrona GK, Gudnason T,
Maeng M, Alstrm P, Andersson J, Calais F, Carlsson
J, Collste O, Gtberg M, Hrdhammar P, Ioanes D,
Kallryd A, Linder R, Lundin A, Odenstedt J, Omerovic
E, Puskar V, Tdt T, Zelleroth E, stlund O, James SK.
Outcomes 1 year a[er thrombus aspiraHon for
myocardial infarcHon. N Engl J Med. 2014 Sep
18;371(12):1111-20. doi: 10.1056/NEJMoa1405707.

TASTE- 1. YIL
Bir yllk takipte primer sonlanm olan tm
nedenli lmler aspirasyon yaplanlarda %5.3,
yaplmayanlarda %5.6 olarak bulunuyor
(p=0.57). Miyokart infarktsyle tekrar
hastaneye yaI ve stent trombozu da iki
grupta benzer kyor.

Mekanik Trombektomi
AIMI (Ali A et al ,JACC 2006;48:244-252)
ReoliHk trombektomi+PKG vs PKG
nfarkt alan (12.5 vs 9.8, p0.03) ve mortalite (%4.6 vs 0.8, p
0.02) daha yksek

JETSTENT (Migliorini et al, JACC 2010; 56:1298-1306)
Stent ncesi RT vs stent
6 ay MACE dk %11.2 vs %19.4, p 0.011
1 yl olaysz sakalm yksek%85 vs %75, p 0.009

Comparison Of Manual AspiraXon With RheolyXc

Thrombectomy In Acute Myocardial InfarcXon: The Final 6-
Month Results Of The SMART Primary PCI Trial

Comparison Of Manual AspiraHon With RheolyHc

Thrombectomy In Acute Myocardial InfarcHon: The
Final 6-Month Results Of The SMART Primary PCI Trial
Guido Parod, Renato ValenH, Angela Migliorini1,
Nazario Carrabba1,Akiko Maehara, Ruben
Vergara,Benedea Bellandi1, Gary Mintz3, David
Antoniucci,
MAT or RT allow only incomplete removal of thrombus
in the seng of AMI. RT as compared to MAT is more
eecHve in thrombus removal and is associated with a
beer myocardial reperfusion.

ASPRASYON KATETERLER KULLANILIRKEN

DKKAT EDLMES GEREKEN HUSULAR
lemden nce
TIMI trombs snflamas (0-5)

lem Srasnda
Hava Embolisi
-Aspirasyon kateteri kartlrken hava
klavuz kateterde haps olabilir

Damar Anatomisi

Disseksiyon/perforasyon

-Tortyoz

-zellikle distal ve kk damarlarda

-Kalsifikasyon
-Kk damar <2.5 mm
Klavuz kateter destei

Klavuz katetere bal disseksiyon

-Sk bir lezyondan aspirasyon kateteri hzl
bir ekilde ekilirse

Lezyonun yeri (Proksimal-Distal)

Trombs srkleyip brakabilir ; drag and

drop effect
Distal embolizasyon
Distalden aspirasyona balanlrsa
Trombosit aktivasyonuna yol aabilir

Drag and drop effect

Aspirasyon kateteri klavuz kateterden kana
kadar negatif basnta kartlmaldr
Klavuz kateter ile aspirasyon kateteri co-axial
olmaldr. Olmaz ise klavuz kateterin ucunda
taklarak trombsn dmesine sebep olabilir
Aspirasyon kateteri kartldktan sonra klavuz
kateter mutlaka aspire edilmelidir

%10 ASPRASYON BAARISIZ

Belirgin proksimal tortyozite (> 2 kvrm)

Kalsifik lezyon
Bifrkasyon lezyonu
Cx arter

Vink MA et al. J Am Coll Cardiol Intv 2011;4:634-642

PRMER PKG TROMBOASPRASYON

Klavuz tel ile sorumlu lezyon geildikten sonra
AKIM

TIMI 0-1

TIMI 2-3 IC TROFBAN

TROMBOASPRASYON/ANJYOJET
TROMBUS YOUNLUU
AZ
OK
(TIMI TROMBUS <3)
(TIMI TROMBUS 3)
TIMI 0-1 IC TROFBAN TIMI 2-3 IC TROFBAN

DREKT STENT

KK BR BALON LE PREDLATASYON SONRASI TEKRAR

TROMBOASPRASYON/ ANJYOJET
DREKT STENTLEME

TROMBOASPRASYON/
ANJYOJET

GREG W STONE ACC 2012

I IIa IIb III

I IIa IIb III

STYM-Primer PKG
2009
Primer PKG srasnda aspirasyon trombektomi
yaplmas nerilir

STYM-Primer PKG
2011
Primer PKG srasnda aspirasyon trombektomi
yaplmas nerilir

PPKG Manuel
PPKG
manuel trombektomi
trombektomi


IIa
IIa

EXPRA
TAPAS
Metaanaliz Bavry et al

Metaanaliz de Luca et al
Meta analiz Bavry et al
Burzoa F
TAPAS

ESC/EACT 2010 Klavuzu IIA (A)

YEN ORAL ANT-TROMBOST

AJANLAR

Neden yeni anXtrombositer ila?????

.Klopidogrelin akHf metaboliHne dnmesinin
yava olmas, geri dnsz balanmas ve
etkisinin hastalar arasnda deikenlik
gstermesi(geneHk polimorzm) gibi snrllklar
var

.Klopidogrelle ilikili olarak iskemik olay
sklnn ykseldiine iaret eden kantlar
artmaktadr.

ONSET almas
Faz II, ok merkezli, randomize, ift kr, paralel gruplu alma1
Hasta Poplasyonu
Randomizasyon

123 hasta
18 yanda
Belgelenmi stabil KAH
Devam eden ASA tedavisi
(75-100 mg/gn)

Tikagrelor
90 mg, 6 hafta sreyle gnde iki kez
180 mg ykleme dozu ile
Klopidogrel 75 mg, 6 hafta sreyle gnde bir
600 mg ykleme dozu ile

Plasebo (n=11)*
* Tm hastalara ASA verildi.

Balang
(1. gn)
Ykleme dozu

1. Gurbel PA, et al. Circulation 2009;120:2577-85.

Tedaviye Devam
(6 hafta)

Sonlanm
(10. gn)
Son doz

Conclusions
First study to comprehensively characterize onset and offset of the
antiplatelet effect of ticagrelor compared with clopidogrel in stable
CAD patients.
3 Major Findings:
- Ticagrelor onset is very rapid and markedly greater than high loading
dose clopidogrel
- Greater inhibitory eect of Hcagrelor is sustained during
maintenance
- Ticagrelor oset as determined by IPA slope was signicantly faster
than clopidogrel
These eects may explain the lower occurrence of the primary
endpoint with Hcagrelor therapy as compared to clopidogrel therapy
in PLATO whereas numerically less CABG-related bleeding occurred
in the Hcagrelor group despite greater platelet inhibiHon.

Tikagrelor 30 dakikada %41lik IPA deerine ulamtr.1

Ykleme Dozu Sonras 30. Dakika IPA Oranlar1

Tikagrelor 180 mg
ykleme dozu
(n=54)

Klopidogrel 600 mg
ykleme dozu
(n=50)

%41 IPA

%8
IPA

1. Gurbel PA, et al. CirculaHon 2009;120:2577-85.

Tikagrelor 2. saatte %88lik IPA deerine ulayor.1

Ykleme Dozu Sonras 2. Saat IPA Oranlar1

Tikagrelor 180 mg
ykleme dozu
(n=54)

Klopidogrel 600 mg
ykleme dozu
(n=50)

1. Gurbel PA, et al. CirculaHon 2009;120:2577-85.

%88 IPA

%38 IPA

PLATO almas Tasarm1,2

Tikagrelor (n=9,333)

N=18,624
AKSli hastalar
(UA, NSTEM
ya da STEM)

180-mg ykleme dozu

90 mg 2x1 + ASA idame dozu

300-mg ykleme dozu

75 mg 1x1 + ASA idame dozu

Klopidogrel (n=9,291)

Primer etkililik
sonlanm:
Kardiyovaskler
lm, M ve
inme bileimi
Primer
gvenlilik
sonlanm:
Toplam PLATO
majr kanama

Randomizasyon

Tarama

Vizit 2

Vizit 3

Vizit 4

Vizit 5

Vizit 6

<24 saat 1. Ay

3. Ay

6. Ay

9. Ay

12. Ay

Daha nce klopidogrel ile tedavi edilmemi olan hastalarda 300 mg ykleme dozunda klopidogrel verilmesine gz yumuldu,
buna ek olarak aratrmacnn kararna gre ek 300 mg daha verilmesine izin verildi.

1. James S, et al. Am Heart J 2009;157:599-605. 2. Wallentin L, et al. N Engl J Med 2009;361:1045-57.

TU-47-272-Ekim-2013

PLATO almasnn Tasarm1,2

PLATO almas: zet

zet

Toplam 18,624 AKSli hasta, hastaneye bavurmalarndan ksa bir

sre sonra - semptomlarn balamasndan sonraki 24 saat iinde ve
genellikle anjiyografi yaplmadan nce - randomize edildi.1,2
PLATO almas klinik uygulamay yanstacak biimde tasarland.1-3
Daha nce klopidogrel kullanlm olan hastalar da almaya alnd.
almaya hem invazif tedavi (%72) hem de medikal tedavi (%28) gruplar
dahil edildi.
PKG ncesi 600 mga dek ykleme dozu uygulanabildi.

AKSli geni bir hasta grubu alnd (UA, NSTEM ya da STEM).1,2

1. James S, et al. Am Heart J 2009;157:599-605. 2. Wallentin L, et al. N Engl J Med 2009;361:1045-57. 3. 3. Cannon CP, et al. Lancet
2010;375:283-93.

TU-47-272-Ekim-2013

PLATO, tikagrelor ile gnmzdeki standart tedavide kullanlan

klopidogreli karlatran bir klinik almayd.1,2

Tikagrelor, 1. aydaki KV lm, M ve inme bileik sonlanmn

klopidogrele gre anlaml oranda azaltmtr.1
1. Ayda Bileik Sonlanm Riski

%0.6
%12
RRR

%5.4
%4.8
HR
0.88

%95 GA
0.77-1.00

P deeri
0.045

Her iki grupta da ASA kullanld.

ARR: Mutlak risk azalmas, RRR: Rlatif risk azalmas
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.

Tikagrelor (n=9333)
Klopidogrel (n=9291)

TU-47-272-Ekim-2013

ARR

Tikagrelor ile klopidogrele gre erken dnemde salanan

mutlak risk azalmas 1 yllk tedavi sresince devam etmi.1
1. Ylda Primer Bileik Sonlanm Noktas
%11.7

%1.9
ARR

%16
HR
0.84

%95 GA
0.77-0.92

P deeri
<0.001

Tikagrelor (n=9333)

RRR

Klopidogrel (n=9291)

NNT=54

Her iki grupta da ASA kullanld. nme asndan tedavi gruplar arasnda fark yoktur.
ARR: Mutlak risk azalmas, RRR: Rlatif risk azalmas; NNT: Tedavi edilmesi gereken hasta says
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.

TU-47-272-Ekim-2013

%9.8

Tikagrelor, dk doz ASA alanlarda 1. yldaki KV

lm klopidogrele gre %29 azaltmtr.1,2

%29
RRR

HR
0.71

%95 GA P deeri
0.60-0.84 <0.0001

Tikagrelor (n=8025)
Klopidogrel (n=8034)

* 75-150 mg
1. Gemeinsamer Bundesausschuss (2011) TicagrelorDossier zur Nutzenbewertung. http://www.g-ba.de (son eriim tarihi: 01.08.13)
2. Theidel U, et alClin Res Cardiol 2013;102:447-58.

TU-47-272-Ekim-2013

Dk Doz ASA* Alanlarda 1. Ylda KV lm Riski1

PLATO STE-ACS:
Primer ve sekonder sonlanm
noktalar
Olay
KV lm, MI ve inme

Tikagrelor,% Klopidogrel, %
(n=3752)
(n=3792)

HR (95% CI)

p deeri

9.4

10.8

0.07

9.8

11.3

0.05

13.3

15.0

0.03

MI

4.7

5.8

0.03

KV lm

4.5

5.5

0.07

Inme

1.7

1.0

0.02

Tm nedenlere bal
lm

5.0

6.1

0.05

Total lm, MI ve
inme
KV lm, MI, inme,
iskemi, TIA, arteriyal
thromboz

0.5

1.0
Tikagrelor iyi

ACS, akut koroner sendrom; CI, gven aral ; CV, kardiyovaskler; HR, hazard raHo; MI, miyokart enfarkts;
STE, ST-segment ykselmesi; TIA, geici iskemik atak.
Steg PG, et al. CirculaCon 2010;122:21312141.

2.0
Klopidogrel iyi

STE-ACS hastalarnda Ticagrelora bal primer sonlanm

noktasnda azalma PLATO genel sonular ile uyumludur
PLATO STE-ACS: Primer Birleik sonlanm noktas1
12

KV lm, MI veya nme (%)

10.8%
10

9.4%

8
6

STE-ACS
BRILINTA (n=3752)
Klopidogrel (n=3792)

HR (95% CI) = 0.87 (0.751.01)

P=0.07

2
0
0

10

12

Randomizasyon sonras aylar

PLATO almas genel primer sonlanm noktas: HR: 0.84; 95% CI: 0.770.92; P<0.0012
1. Steg PG et al. CirculaHon 2010;122:21312141; 2. WallenHn L et al. N Engl J Med 2009;361:10451057

92

TRITON-TIMI 38: Hasta alm emas

UA/NSTEMI semptom
balangc sonras
72 saat ve TRS 3

STEMI semptom
balangcndan 12 saat -
14 gn sonra (Post-
STEMI)

STEMI semptom
balangc sonras
12saat
(Primer PKG)

DiyagnosXk Kateterizasyon
PKG plan
Medikal
tedavi veya
CABG plan

Randomize etme

Randomizasyon
alma lac Ykleme Dozu

PKG*
* Elik eden tedavi ve cihaz
seimi hekim insiyatifinde

Gnlk dame Tedavisi & Uzun Dnem Takip

Wiviott SD et al. Am Heart J 2006;152:627-635

TRITON-TIMI 38 almas 12.ay verilerine gre:

Majr kanama oranlar klopidogrelden farkszdr
Tm Kohort

Wilcox R et al. Current Medical Research & Opinion 2014; 1-13

10 mg Endike Kohort Grubu

TRITON-TIMI 38:

Primer sonlanm noktasnda %19 azalma

15

Sonlanm noktas (%)

Klopidogrel
KV lm, MI, nme

10

%19
RRR

Prasugrel
5

Non-CABG
TIMI majr kanamalar

30 60 90 120

180

Prasugrel

270

360

Randomizasyon sonra geen sre (gn)

Wivio SD et al. New Engl J Med 2007;357:2001-2015

9.9 (643)
p<0.001
138 olay
p=0.03
35 olay

Klopidogrel
0

12.1 (781)

2.4 (146)
1.8 (111)
450

TRITON-TIMI 38
prasugrel Ykleme Dozu

Wiviott SD et al. Am Heart J 2006;152:627-635

Prasugrel ykleme dozu:

Mmkn olduunca erken veya PKG srasnda

AHA/ACC STEMI Klavuzu, 2013

TRITON-TIMI 38

<75 Ya, 60 kg ve inme/GA yks olmayan hastalarda

Primer sonlanm noktasnda %26 azalma
1 6

KV lm / lmcl olmayan MI /
lmcl olmayan inme

Son nokta (%)

1 4
1 2

Klopidogrel 11%

Risk oran, 0.74

(%95 CI, 0.66-0.84)
P<0.0001

1 0

% 26
RRR

NNT
37

Prasugrel

8.3%

6
4

Risk oran, 1.24

(%95 CI, 0.91-1.69)
P=0.17

2
0

Bypass a bal olmayan

TIMI Majr Kanama

Prasugrel 1.95%
Klopidogrel 1.50%

30

NNT: number needed to treat

90

180

270

Sre (Gn)

Wivio SD et al. Am J Cardiol 2011;108(7):905-11

360

450

STEMI Kohort (N = 3534)

Hasta (%)

Prasugrel STEMI hastalarnda 30.gnde KV lm ve

tm nedenli lmleri anlaml olarak azaltmr.

Montalescot G. et al. Lancet 2009; 373: 723-31

TRIPLET almas: 60 mg prasugrel ykleme dozu AKS-PKG

hastalarnda klopidogrel 600 mg + prasugrel 60 mg ykleme dozu ile
benzer trombosit inhibisyonu salamr

DiodaX, et al. Circ Cardiovasc Interv 2013;6:567-74.

SWAP almas:
Klopidogrel idame tedavisinden prasugrele hem yklemeli hem
yklemesiz gei, anXagregan etkinlii arrr.

Placebo LD/Clopidogrel 75 mg MD (N=33)
Placebo LD/Prasugrel 10 mg MD (N=36)
Prasugrel 60 mg LD/10 mg MD (N=31)

VN-P2Y12 PRU

200

150

100

50

*
0

0 2

*
12

24

saat
*p<0.0001 vs. klopidogrel 75 mg MD; p<0.0001 vs. prasugrel 10 mg MD
LD=Ykleme Dozu; MD=dame Dozu; PRU=P2Y12 ReakHvite nitesi
Angiolillo DJ et al. JACC 2010; 56(13):1017-23.

10 12 14
gn

The DAPT Study was designed in response to a request from the FDA to
evaluate the eect of dual anXplatelet therapy beyond one year in subjects

treated with coronary stents

DAPT-CONCLUSIONS
Following drug-eluHng stent treatment, conHnuaHon of
thienopyridine plus aspirin beyond one year reduces the risk of
stent thrombosis and MACCE compared with aspirin alone.

RelaHve reducHons of 71% for ST, 29% for MACCE and 53% for M
Myocardial infarcHon reduced both in the stent and in other locaHons
Treatment benet on ST and MI consistent across drugs, for newer
and older stents, and across subjects with higher or lower risk of
events

The benet of extended thienopyridine treatment was tempered

by an increase in bleeding events (relaHve increase, 61%). Severe
and/or fatal bleeding was uncommon.

ESC Miyokardiyal Revasklarizasyon Klavuzu

ESC Miyokardiyal Revasklarizasyon Klavuzu

2014 AHA/ACC NSTE-ACS Klavuzu

Tikagrelor

Tikagrelor ile nerilen idame ASA dozu 81 mgdir.

1. 10. 2013 ACCF/AHA Guideline for the Management of ST-ElevaHon Myocardial InfarcHon. CirculaHon 2013;127:00-00.
DOI: 10.1161/CIR.0b013e3182742c84

TU-47-272-Ekim-2013

Tikagrelor

EVE GTRLECEK MESAJLAR

Distal embolizasyon primer PCI da sklkla
karmza kabilir ve azalm miyokardiyal
perfzyon ve kt klinik sonularla ilikilidir.
GPI ile farmakolojik stratejilerin ilem baars
zerine olumlu etkileri zellikle yksek riskli
hastalarda belirgindir. IC. Kullanm etkinlii
arrabilir
Manual aspirasyon cihazlar basit, hzl kullanm
olup, 1 yllk klinik sonular olumlu etkileyebilir

EVE GTRLECEK MESAJLAR

Yeni anHtromboHk ajanlar Primer PKG da ilk
seenek olmal