Thrombolysis is preferred mode of reperfusion during the first 2 hours CONTRA

Transkrypt

1 Thrombolysis is preferred mode of reperfusion during the first 2 hours CONTRA Dariusz Dudek Department of Interventional Cardiology, Institute of Cardiology, Krakow, Poland The European Association on Percutaneous Cardiovascular Interventions (EAPCI ESC ) Chair, The Scientific Programme Committee

2 Primary PCI vs lysis Meta-analysis of 23 randomized studies - immediate results n= p= p= p< p< p= p< p=0.032 p< PTCA (n=3872) % 15 Lysis (n=3867) death 9 5 death without shock remi 6 Recurr ischemia stroke ICH severe bleeding death, remi, stroke Keeley EC; LANCET 2003

3 30-day mortality (%) Time & Mortality Primary PCI vs. Thrombolysis Primary PCI 4 2 Thrombolysis Onset of pain to treatment (hours) 7 8 Eur Heart J 2005;26:

4 12 miesięczna śmiertelność (%) Time from Symptom Onset to Treatment Predicts 1-year Mortality after Primary PCI 12% 10% 8% EVERY MINUTE OF DELAY COUNTS 6% 4% 2% p< % czas ischemii (min) The relative risk of 1-year mortality increases by 7.5% for each 30-minute delay G. De Luca, Circulation 2004

5 Mortality Reduction, (%) Patient < 2h from symptoms onset What is the difference? Mortality Reduction (%) 100 Critical Time-dependent Period Goal: Myocardial Salvage D C Time-independent Period Goal: Open Infarct-related Artery 20 B A Extent of Salvage (% of area at risk) Time From Symptom Onset to Reperfusion Therapy (hours) Gersh BJ, et al. JAMA. 2005;293:

6 PCI as preffered reperfusion therapy. ESC Guidelines Time FMC to first balloon inflation must be shorter than 90 min in patients presenting early (<2 h after symptoms onset), with large amount of viable myocardium and low risk of bleeding

7 EUROPE LOW RATE OF NO REPERFUSION HIGH RATE OF NO REPERFUSION HIGH RATE OF P-PCI LOW RATE OF P-PCI Eur Heart J Nov 19 [epub ahead of print]

8 Comparison of mortality among STEMI patients receiving prehospital thrombolysis or primary PCI with in-hospital thrombolysis, JAMA Vol. 296 No. 14, October 11, 2006

9 Estimated cumulative mortality for patients receiving reperfusion therapy <2 hours of symptoms onset JAMA Vol. 296 No. 14, October 11, 2006

10 30-day mortality (%) Time & Mortality Primary PCI vs. Thrombolysis Trends favoring Thrombolysis * Eur Heart J. 2003;24(1): ** Circulation. 2003;108(23): *** Circulation 2006;113: <3h >3h <2h >2h <2h >2h <3h >3h PRAGUE-2* CAPTIM* VIENNA* VIENNA* PPCI TT but

11 70% of Fibrinolysis patients was finally treated with PCI Cardiogenic shock patients excluded (who potentially have large benefit of PCI over Lysis) the unspecified subgroup analysis, the use of a portion of the primary end point (30-day mortality), the small number of end points, and the borderline nominal significance test make this analysis hypothesis generating rather than hypothesis testing. Results of prehospital lysis does not translate to in-hospital lysis Patients enrollment in different era of Primary PCI

12 Vienna STEMI registry Changes in reperfusion strategies

13 D2N time what about 30 minutes? Author % of patients treated with D2N<30 minutes Lambert L et al. JAMA % Spencer FA et al. GRACE Reg EHJ % Glickman SW et al. AHJ % Vasaiwala S et al. JACC % Time delay seems to be a problem not only of Primary PCI

14 Strategy selection in STEMI < 2h PCI <90min possible Primary PCI

15 Primary PCI vs. Thrombolysis Influence of time from chest pain onset [%] FL PCI 30-days mortality 4,3% ,3% Door to needle 19 min Door to balloon 76 min PCI delay 55 min (37-74) >1-2 >2-3 >3-6 >6-12 Metaaanalysis of 23 studies, 6763 patients E. Boersma i PCAT-2 Eur Heart Journal 2006, 27; 779

16 EUROTRANSFER Registry European Registry on Patients with ST-Elevation MI Transferred for Mechanical Reperfusion (PCI) with a Special Focus on Upstream Use of Abciximab Early abciximab Late abciximab 15 STEMI hospital networks from 7 countries across Europe 1650 patients (Nov untill Jan. 2007) Median time from abciximab to balloon in Early Abciximab (n=727) and Late Abciximab group (n=359): 75.5 vs 20.5 minutes 15% 10% 5% 2.8% p=0.012 p=0.01 p= % 7.5% 5.9% 5.5% 3.9% 0% Death in-hospital Death at 30 days Death+reMI+PCI/CABG at 30 days Conclusions: First study that reports a significant association of lower in-hospital and 30- day mortality with early (in referral hospital or ambulance) start of abciximab in a real life setting of STEMI hospital networks in Europe Am Heart J. 2008;156: Principal Investigator: Dariusz Dudek; Study Coordinators: Zbigniew Siudak, Lukasz Partyka

17 Prognostic Significance and Magnetic Resonance Imaging Findings in Aborted Myocardial Infarction after Primary Angioplasty Aborted MI in 58 of 420 pts (14%) American Heart Journal. 2009;158(5):

18 Strategy selection in STEMI < 2h PCI <90min NOTpossible Lysis may be an option but

19 Contraindications to Lysis

20 Risk of ICH across the major RCTs with fibrynolytic agents The risk of ICH associated with fibrynolysis ~0,9% GUSTO III In-TIME II ASSENT 2 ASSENT 3

21 Thrombolysis is NOT: for every patients the last step of reperfusion so effective when administered in-hospital after transportation (only reasonable way is early pre-hospital administration)

22 Early (within 24 hours) or delay (>24 hours) invasive strategy after thrombolysis in STEMI? 60 P=0, MACE delayed PCI PCI <24h p=0,0008 p=0,04 p=ns p=0,001 p=0,001 0 SIAM III GRACIA I CAPITAL AMI n=197 n=500 n=170 LPLS n=164 CARESS in AMI n=600 TRANSFER AMI Death, Recurrent ischemia, TLR Death, remi, TLR Death, remi, Recurrent ischemia, TLR Death, remi, major bleedings Death, remi, Recurrent ischemia Death, remi, CHF, Recurrent ischemia, shock JACC 2003 Lancet 2004 JACC 2005 EHJ 2005 Lancet 2008 ACC 2008

23 Primary Outcome at 30 days Death, re-mi, refractory ischaemia 11.1% OR 0.34 (95%CI ) P= % FACILITATED PCI Med. Treatment/Rescue p n= 294 n= 298 Death, re-mi, refract isch (adjudicated) 12 (4.1) 33 (11.1) =0.001 Death, re-mi, refract isch (unadjudicated) 15 (5.1) 42 (14.1) <0.001 Di Mario, Dudek, Piscione, et al. Lancet 2008, 371

24 PCI at non-pci centres: immediate or rescue? CARESS-in-AMI study EDITORIAL Pending these results, organisation of networks to move patients given a thrombolytic drug to institutions with catheterisation laboratories seems a reasonable option, since primary angioplasty cannot be implemented everywhere. Nicolas Danchin, Paul W Armstrong LANCET 2008; 371:

25 Stent for Life Deliverables To increase the use of primary PCI towards >70% use among all STEMI patients To achieve primary PCI rates >600 / million per year in most European countries Empower PCI centers to offer 24/7 services for primary PCI

26 Prehospital management DRIP & SHIP FAST TRANSFER NO MORE SELF TRANSPORTATION NO MORE TRANSFERS FROM NON-PCI HOSPITALS

27 Krakow and Malopolska Networks Decentralization Networks for population with: shorter time since first medical contact to balloon time predefined patients transfer rules Consultations, quality control, training programs by University Center Targets: reduce time delay to reperfusion, increase reperfusion rate

28 Krakow & Malopolska Registry (total = 3,2 mln population) Primary PCI for STEMI/ 1 milion population in 2009 STEMI 672/milion p. olkuski 114,7 tys. Krakó w + p. STEMI 911/milion p. miech owski 51,5 tys. p. dąbro wski 58,6 p. tys. STEMI 750/milion krakow boche ski p. ński wielick p. Tarnów 998,8 i 99,7 tys. 102,5 brzesk + tys. tys. i 89,7 tys. p. limano wski 120,2 tys. STEMI 660/milion p. tarnow ski 310,5 STEMI 692/milion tys. p. gorlicki 106,4 tys. NETWORKS OF HOSPITALS FOR EARLY INVASIVE DIAGNOSIS AND TREATMENT OF ACUTE CORONARY SYNDROMES

29 Malopolska Registry of Acute Coronary Syndromes Time delays in a small network 0.5 million population Nowy Sacz p. limanowski 120,2 tys. 506 tys. Nowy Sącz + p. nowosądecki 279,4 tys. p. gorlicki 106,4 tys. FMC cathlab Cathlab balloon FMC balloon 34 ± 23 min (median = 30 min) 32 ± 9 min (mediana = 30 min) 66 ± 26 min (mediana = 60 min)

30 Malopolska Registry of Acute Coronary Syndromes Treatment strategies in small Network 0.5 million population Nowy Sacz STEMI < 12 godz. p. limanowski limanows 120,2 tys. ki 120,2 tys. 506 tys. Nowy Sącz + p. nowosądecki 279,4 tys. p. gorlicki gorlicki 106,4 tys. 106,4 tys. PRIMARY PCI THROMBOLYSIS NO REPERFUSION Dudek D. et al. Kardiol. Pol. 2008;66:

31 Organizacja interwencyjnego leczenia pacjentów z zawałem serca STEMI i NSTEMI w Polsce Ostry zespół wieńcowy Ostry Zespół Wieńcowy Uniesienie odcinka ST w EKG Ostry Zespół Wieńcowy Brak uniesienia odcinka ST w EKG Bezpośredni kontakt telefoniczny z najbliższą pracownią hemodynamiki pełniącą całodobowy dyżur zawałowy Zgoda kardiologa inwazyjnego na transport TAK Bezpośredni transport <24h! Transport do najbliższego SOR Jedno z poniższych kryteriów: Niestabilność hemodynamiczna Komorowe zaburzenia rytmu VF/VT Nawrót niedokrwienia z obniżkami ST 2mm Utrzymujący się mocny ból zawałowy wskazujący na duże niedokrwienie Podniesiony poziom troponiny, dynamiczne zmiany ST, Cukrzyca, EF<40, po PCI, po CABG, GFR <60ml/min/1.73m2, Dusznica pozawałowa, GRACE score>140 Bezpośredni transport do najbliższej pracowni hemodynamiki pełniącej całodobowy dyżur zawałowy: NIE Nieinwazyjna ocena niedokrwienia na oddziale szpitala bez pracowni hemodynamiki Planowa diagnostyka inwazyjna naczyń wieńcowych Uwaga! Gdy spodziewany długi czas opóźnienia związany z transportem rozważyć transport lotniczy Inne rozpoznanie Statement based on Malopolska Registry experience

32 Malopolska region Tarnow network Results before and after regional AMI program BEFORE AFTER Kraków + p. krakowsk i 998,8 tys. p. wielicki 102,5 tys. p. bocheńsk i 99,7 tys. p. dąbrows ki 58,6 tys. Tarnów + p. brzeski p. 89,7 tys. tarnowski 310,5 tys. STEMI p. wielicki 102,5 tys. p. bocheńsk i 99,7 tys. p. dąbrows ki 58,6 tys. Tarnów + p. tarnowski 310,5 tys. Dudek D, Janus B

33 Current ESC STEMI & PCI Guidelines vs Focused Updates of ACC/AHA STEMI Guidelines & ACC/AHA/SCAI PCI Guidelines Triage and transfer for PCI ESC STEMI 2008 (1) ACC/AHA focused updates 2009 (2) The implementation of network of hospitals connected by an efficient ambulance (helicopter) service and using a common protocol is key an optimal management of patients with STEMI. With such a network in place, target delay times should be: <10 min for ECG transmission; 5 min for tele-consultation; <30 min for ambulance arrival to start fibrynolytic therapy; and 120 min for ambulance arrival to first balloon inflation. Quality of care, appropriateness of reperfusion therapy, delay times and patients outcomes should be measured and compared at regular times and appropriate measures for improvement should be taken. (discussed but no exact recommendations) Each community should develop a STEMI system of care that follows standards at least as stringent as those developed for the AHA s national initiative, Mission: Lifeline, to include the following: ongoing multidisciplinary team meetings that include emergency medical services, non PCI-capable hospitals/stemi referral centers, and PCI-capable hospitals/stemi receiving centers to evaluate outcomes and quality improvement data; a process for prehospital identification and activation; destination protocols for STEMI receiving centers; transfer protocols for patients who arrive at STEMI referral centers who are primary PCI candidates, are ineligible for fibrinolytic drugs, and/or are in cardiogenic shock. (IC) 1 Eur Heart J. 2008;29(23): Circulation. 2009;120:

34 Conclusions Primary PCI reduces mortality in AMI patients =the best reperfusion method Network based Primary PCI program allows to increase reperfusion therapy rate High number of patients = high experience Well organized networks allows to reduce time delays =the best reperfusion method - for high number of patients in short time window When anticipated delay to Primary PCI is more than min thrombolytic therapy is an option but with immediate transfer to cath lab hospital

35 Conclusions Primary PCI is preferred method of reperfusion Prehospital lysis may be an option if PCI related delay is very large Lysis is not the last step of reperfusion (CARESS, TRANSFER AMI) Lysis has important limitations: contraindications, bleeding complications, lower success rate