Reperfusion in STEMI. Pharmacoinvasive therapy The Krakow experience

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Reperfusion in STEMI Pharmacoinvasive therapy The Krakow experience Dariusz Dudek Jacek Legutko,, Jarosław Zalewski, Krzysztof śmudka Institute of Cardiology Jagiellonian University Medical College Krakow, Poland

Jagiellonian University Institute of Cardiology, Krakow, Poland 2 hospitals 5 cathlabs 26 Interventional Cardiologists 4000 PCIs / year 1500 PCI in STEMI / year

ESC guidelines (march 2005) STEMI (within 12 hours after onset of symptoms) Patient presenting in a hospital with PCI 3 12 h Patient presenting in a hospital without PCI <3 h Immediate transfer Thrombolysis Failed Successful PCI 24h available PCI 24h not available Predischarge ischaemia Primary PCI Rescue PCI Post thrombolysis PCI Ischaemiaguided PCI

How to Optimize Primary PCI? Improvement of myocardial reperfusion Gp IIb/IIIa proven efficacy (class IIaA) mechanical protection thrombectomy, distal and proximal protection (class IIb C). No routine use, but: Better ST resolution, MPG no MACEs improvement, no EF? Reduction of TVR during long term follow up DES

Acute MI < 12 hrs in the region of 3.2 mln inhibitants Ia Ib transfer < 90min (Ib) transfer < 30min (Ia) TELE EKG abciximab Cathlab Thrombectomy and PCI PCI and abciximab PCI

Impact of Early Abciximab Administration before Primary Percutaneous Coronary Interventions in Anterior Myocardial Infarction on Reperfusion and Left Ventricular Function (n=59 pts) BASELINE ANGIOGRAPHY 80% 60% 48% 40% 20% p=0.04 20% Early Abciximab Late Abciximab STSEGMENT RESOLUTION 60min AFTER PCI 100% 80% 60% 40% 20% 84% p=0.04 56,7% 52% p=0.04 23,3% 0% TIMI 2+3 0% STR>50% STR>70% 500 400 300 200 100 0 AUC 5938+/3949 3949 U/l x h CKMB AUC during 48h AUC 8324+/4185 4185 U/l x h p=0.04 0 4 8 12 16 20 24 30 36 42 48 CARDIAC MAGNETIC RESONANCE AT 1 YEAR 60 50 40 30 20 10 0 p=0.02 LEFT VENTRICULAR ESVI END SYSTOLIC VOLUME INDEX T.Rakowski, D. Dudek et al., AJC 2005 (TCT oral presentation)

EUROTRANSFER Registry European Registry on Patients with STElevation MI Transferred for Mechanical Reperfusion (PCI) with a Special Focus on Upstream Use of Abciximab. Principal Investigator Dariusz Dudek MD, PhD Director, Cardiac Catheterization Laboratories University Hospital, Krakow, Poland

EUROTRANSFER Registry currently participating centres Helsinki FINLAND Linkoping SWEDEN Przemysl POLAND Krakow POLAND Zabrze POLAND Rostock GERMANY Villingen Schwenningen GER Leeds ENGLAND Santiago de Compostela SPAIN Coruna SPAIN Treviso ITALY Reggio Emilia ITALY Mantova ITALY Arezzo ITALY Ljubljana SLOVENIA Nowy Sacz POLAND Tarnow POLAND Massa ITALY Brussels BELGIUM Lund SWEDEN Bad Oeynhausen GERMANY

PolishItalianHungarian Randomized ThrombEctomy Trial PIHRATE Trial PI: Dariusz Dudek

PIHRATE Trial n=200 pts STEMI <6hr ST elevation >3 mm in one lead TIMI 0 or 1 TIMI, ctfc, MBG RANDOMIZATION TIMI 0 or 1 POBA STENTING Grup I (n=100) THROMBECTOMY TIMI, ctfc, MBG TIMI 2 or 3 DIRECT STENTING TIMI, ctfc, MBG Grup II (n=100) PREDILATATION TIMI, ctfc, MBG STENT IMPLANTATION TIMI, ctfc, MBG ST SEGMENT RESOLUTION 60 MINUTES AFTER PCI CK/CKMB LEAK: every 6 hours for 24 hours ECHO: EF, ESV, EDV, WMSI predischarge and 6 month follow up CMR in the subgroup of patients EDV, ESV, mass and ejection fraction, delayedcontrastenhancement 6 months follow up MACE: 30 day and 6 month follow up

Delay >60 minutes 6090 (120) minutes >90 (120) minutes ASA / 600mg clopidogrel / UFH TIME DELAY TRANSFER WITH LYTIC / GPIIbIIIa inhibitor / COMBO THERAPY TRANSFER WITHOUT LYTIC / GPIIbIIIa inhibitor / COMBO THERAPY

Why to transfer patients after lytic therapy, when delay to PCI > 120 min? 1. No recommendation in guidelines to transfer patients without lytic with delay >120 min 2. Conservative treatment in hospitals without cath labs provides inferior results to PCI 3. When rescue PCI is necessary patient will be in high volume center (why to keep high risk patients 6090 minutes longer in local hospitals for reperfusion assessment in ecg?) 4. Post lytic PCI within 24 hours is recommended in guidelines

p. miechowski 51,5 tys. p. olkuski 114,7 tys. mortality 3.5% Kraków + p. krakowski 998,8 tys. p. proszowicki 43,6 tys. p. dąbrowski 58,6 tys. 2001 year p. oświęcimski 153,1 tys. p. chrzanowski 128,7 tys. p. wadowicki 153,4 tys. pierwotna PCI p. wielicki 102,5 tys. p. myślenicki 114,9 tys. p. suski p. limanowski 81,5 tys. 120,2 tys. p. nowotarski 179,9 tys. p. bocheński 99,7 tys. Tarnów + p. brzeski p. tarnowski 89,7 tys. 310,5 tys. Nowy Sącz + p. nowosądecki 279,4 tys. p. gorlicki 106,4 tys. 23 hospitals referring STEMI pts to Krakow Center ½ tpa +abciximab and transfer FACILITATED PCI p. tatrzański 65,3 tys.

2 years June 2001 June 2003 STEMI n=2362 (age <75 years) PRIMARY PCI vs FACILITATED PCI 30day MACE 8% 6% 4% 3,4% 3,0% NS 4,2% 3,9% 5,0% 4,8% 2% 0,8% 0,9% 0,8% 0,9% 0% Death re MI re PCI death + re MI All MAC E PRIMARY FACILITATED D. Dudek et al., AJC 2003 D. Dudek et al., AHA 2005, featured research

Primary PCI vs. ReducedDose Facilitated PCI Death Reinfarction Revascularization Bleeding P Value Facilitated Lytic Alone P Value Facilitated Lytic Alone P Value Facilitated Lytic Alone P Value Facilitated Lytic Alone Authors Titles Ross et al. PACT 3.3% 3.6% 0.81 2.6% 3% 0.80 7.2% 7.3% 0.98 13.5% 12.9% 0.84 Dudek et al. 3.5% 1.0% 1.5% 3.0% Kastrati et al. BRAVE 1.6% 1.6% NS 0% 0.8% NS 1.6% 5.6% 0.16 Maioli et al. 6.1% 6.3% 0.195 1% 0% 0.560 3% 6.2% 0.226 ADVANCE MI Inv. ADVANCE MI 0% 6.8% 0.03 2.7% 1.4% 0.33 10.8% 23% 0.05 Borden and Faxon, J Am Coll Cardiol, 2006;48:1120 8

ST,, high risk, lytic lyticeligible, < 12 12 h UFH UFH 40 40 U/kg U/kg (max (max 3000); 3000); 7 U/kg/h U/kg/h Reteplase 2 x 5 U bolus bolus (30 ) (30 ) Abciximab 0.25 0.25 mg/kg mg/kg bolus; bolus; 0.125 0.125 µg/kg/min µg/kg/min x 12 12 h (maximum 10 µg/min) (maximum 10 µg/min) IMMEDIATE PCI Immediate Transfer Transfer to to Cath CathLab for for PCI; PCI; after after PCI PCI pat. pat. remains remains in in the the hospital hospital where where PCI PCI was was performed or or is is transferred back back to to referring hospital hospital MEDICAL TREATMENT + RESCUE CCU CCU Admission; Transfer Transfer for for PCI PCI only only if if persistent ST ST elevation at at 90 90 min min (>50% (>50% basal basal ECG), ECG), chest chest pain pain or or hemodynamic compromise Primary Endpoint: Death, Reinfarction,, Refractory Ischemia at at 30 30 Days Days Di Mario, Bolognese, Maillard, Dudek et al Am Heart J, 2004

2 new centers with 24h/7days service for 0.5 mln population each p. oświęcimski 153,1 tys. p. chrzanowski 128,7 tys. p. wadowicki 153,4 tys. p. olkuski 114,7 tys. p. miechowski 51,5 tys. p. proszowicki Kraków + 43,6 tys. p. krakowski 998,8 tys. 2 287,2 tys. SMALL NETWORK for 0.5 mln inhabitatns p. bocheński 99,7 tys. p. wielicki 102,5 tys. p. brzeski 89,7 tys. app. 350 STEMI PCI/ year app. 350 NSTEMI/UA PCI/ year 45 operators p. dąbrowski 58,6 tys. Tarnów + p. tarnowski 310,5 tys. 458,8 tys. 2005 year FACILITATED PCI CARESS study p. suski 81,5 tys. p. nowotarski 179,9 tys. p. myślenicki 114,9 tys. p. tatrzański 65,3 tys. p. limanowski 120,2 tys. 506 tys. Nowy Sącz + p. nowosądecki 279,4 tys. p. gorlicki 106,4 tys. SMALL NETWORK for 0.5 mln inhabitatns app. 350 STEMI PCI/ year app. 350 NSTEMI/UA PCI/ year 45 operators

Primary PCI Clinical usefulness of different thrombectomy devices during primary PCI needs further clinical trials DES for Primary PCI need large clinical studies with long term outcome

Gp IIb/IIIa inhibitors and Primary PCI 1. In STEMI patients, pharmacologic pretreatment prior to PCI improves initial TIMI3 flow 2. It is reasonable to start GPIIb/IIIa as early as possible prior to primary angioplasty 3. Early IIb/IIIa administration could be more beneficial for higher risk AMI, early presenters and when time to PCI is longer (app. 60 minutes door to balloon time)

Fibrynolysis & PCI 1. Facilitated PCI with full dose lytic is not recommended (early routine PCI<12 hrs and immediate after lysis) 2. Pharmaco invasive therapy is permitted and recommended by ESC guidelines (PCI within 24 hrs after lysis). 3. Pharmaco invasive therapy could be recommended for STEMI < 23 hrs onset when long delay > 120 minut expected 4. High risk pts after lytic should be tranfered to PCI centers for clinical/angio evaluation (rescue PCI; PCI 24 hrs)