Koronária intervenciók és antitrombotikus kezelés újdonságai. Dr. Becker Dávid Semmelweis Egyetem Szív- és Érgyógyászati Klinika

Koronária intervenciók és antitrombotikus kezelés újdonságai Dr. Becker Dávid Semmelweis Egyetem Szív- és Érgyógyászati Klinika Székesfehérvár 2019

Antithromboticus kezelés PCI során MIT CSINÁLUNK? MITŐL FÉLÜNK? Stentthrombosis Vérzés Előkezelés TAG ACS + PCI esetén Speciális helyzetek Utókezelés PCI után meddig? DES után meddig? Ha anticoagulatio is szükséges

Antithromboticus kezelés PCI során MIT CSINÁLUNK? MITŐL FÉLÜNK? Stentthrombosis Vérzés Előkezelés Utókezelés PCI után meddig? DES után meddig? Ha anticoagulatio is szükséges

STENTTHROMBOSIS!!!! 100 % INFARCTUS 50 %-os mortalitás! Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse SHAHROKH FALATI, PETER GROSS, GLENN MERRILL-SKOLOFF, BARBARA C. FURIE & BRUCE FURIE Center for Hemostasis and Thrombosis Research, Beth Israel

Early Stent Thrombosis is Associated with Impaired Response to Antiplatelet Therap Bare Metal Stents Wenaweser et al. JACC 2005 Drug-Eluting Stents Sibbing et al. JACC 2009 Multiple Electrode Platelet Aggregometry -1608 patients between 02/2007 and 04/2008 P<0.0001 P=0.13 P<0.0001 % ASA ASA and Clopidogrel

2006 DES BOMBA Késői inkomplett endothelisatio első generációs! DES esetében (TAXUS, CYPHER) = élethosszig kettős TAG 9

A túlélés és a vérzés közötti összefüggés PCI esetén: 30 napos eredmények 1 0.95 0.9 0.9 PURSUIT és PARAGON B (n=15,858) Nincs Enyhe Mérsékelt 0.85 0.85 0.8 0.75 0.7 0.7 0 5 10 15 20 25 30 Days to Death Log rank p-érték mind a négy kategóriában < 0,0001 Log-rank p-érték a nincs vérzés vs. enyhe vérzés között = 0,02 Log-rank p-érték az enyhe vs. mérsékelt vérzés között < 0,0001 Log-rank p-value a mérsékelt vs. súlyos vérzés között < 0,001 Napok None Mild Moderate Severe Súlyos Rao J. Am Coll Cardiol. 2005:96;1200-1206

Vérzés: Transfusio és prognózis ACS-ben

Restrictiv transfusios stratégia hatása a prognózisra

ISTH Major or CRNM Bleeding Xa. gátlók ACS-ben ASA+clopidogrel mellé: APPRAISE-1: apixaban ISTH Major or CRNM Bleeding HR 2.45 95% CI 1.31 to 4.61 p = 0.005 Apix 10 mg QD Apix 2.5 mg BID HR 1.78 95% CI 0.91 to 3.48 p = 0.09 Placebo Weeks

ATLAS TIMI 51

VORAPAXAR PAR-1 (proteáz-aktivált receptor gátlók) hármas antithromboticus kezelés egy kicsit máshogy

VORAPAXAR vissza a thrombocyta receptor gátlókhoz hármas antithromboticus kezelés egy kicsit máshogy

TAGG kezelés, előkezelés Általában a kettős TAGG-ról Évek óta tudjuk, hogy egyedül nem megy (PCI után!) Kezdetek: aspirin + semmi vagy ticlopidine

Clopidogrel Reduces Major Adverse Cardiac Events after Stenting 1 Odds ratios and 95% CI Odds ratios p value Death 0.44 0.001 MI 0.50 0.001 TVR 0.68 0.035 SAT 0.81 0.30 MACE 0.51 0.001 0.1 1.0 10.0 Clopidogrel better Ticlopidine better The odds ratio plots with 95% confidence intervals (CIs) for the rates of the individual components of the composite end point. MI (myocardial infarction); TVR (target vessel revascularization); SAT (subacute stent thrombosis); MACE (major adverse cardiac events). 1. Bhatt DL et al. J Am Coll Cardiol 2002; 39: 9 14.

Patients with events (%) CLASSICS: Superior Safety Profile of Clopidogrel at 28 Days 1 10 9 8 7 6 5 4 3 2 1 0 9.12% Primary Endpoint * 4.56% p = 0.005 Ticlopidine (n = 340) *Major bleeding complications, neutropenia, thrombocytopenia or early discontinuation of the study drug for non-cardiac adverse events (%) Combined groups 1. Bertrand NE et al. Circulation 2000; 102: 624 9. Clopidogrel (n = 680)

TAGG előkezelés De mi a helyzet az előkezeléssel? Stabil angina pectoris ACS

HEART TEAM!

% 2 1 0 0,8 0,8 www.cardiosource.c 3 2 1 0 3,5 PRAGUE-8 Trial Design: PRAGUE-8 was a randomized trial of clopidogrel administration >6 hours prior to elective angiography (600 mg; n = 513) or delayed clopidogrel administration in the catheterization lab if needed for PCI (600 mg; n = 515) in patients undergoing elective coronary angiography for stable angina. Primary endpoint was death, periprocedural MI, stroke, TIA, or reintervention within 7 days. Death, Periprocedural MI, Stroke, TIA, or 5 Reintervention by 7 Days (p = NS) 4 Clopidogrel Load >6 hours Bleeding (p = 0.02) A. femoralis használata! 1,2 Selective Clopidogrel Only for PCI Results At time of angiography, PCI performed in 29% of patients No difference in primary endpoint of between treatment groups whether evaluating all patients (Figure) or only patients who went on for PCI (2.2% in selective clopidogrel group vs. 1.3% in early, nonselective clopidogrel group) Bleeding events in early, nonselective clopidogrel group vs. selective clopidogrel group overall (Figure) and in PCI cohort (7.2% vs. 0.7%, p = 0.006) Conclusions Among patients undergoing elective coronary angiography for stable angina, early, routine use of clopidogrel loading >6 hours prior to angiography was not associated with difference in death, MI, stroke, TIA, or reintervention within 7 days compared with selective use of clopidogrel during angiography if PCI is required, but was associated with a significant increase in bleeding Even among patients who did undergo PCI (~300 patients), there was no evidence of benefit with early loading dose administration, but bleeding complications increased Presented at ESC 2007

Placebo Arm Clopidogrel Arm Overall Study Design PCI* 28 Days 12 Months Pre-treatment 3-24 h before PCI Clopidogrel 300 mg + ASA (325 mg) Clopidogrel 75 mg QD + ASA 325 mg QD Clopidogrel 75 mg QD + ASA (81-325 mg) QD R Placebo + ASA (325 mg) Clopidogrel 75 mg QD + ASA 325 mg QD Placebo QD + ASA (81-325 mg) QD Plus other standard therapies * Both groups received clopidogrel 75 mg + ASA 325 mg at time of procedure Steinhubl S, Berger P, Tift Mann III J et al. JAMA. 2002;Vol 288,No 19:2411-2420.

Combined Endpoint Occurrence (%) Long-Term (1 Year) Benefits of Clopidogrel in PCI Patients MI, Stroke, or Death ITT Population 15 10 Placebo* Clopidogrel* 11.5% 8.5% 27% RRR P=0.02 5 0 0 3 6 9 12 Months From Randomization * Plus ASA and other standard therapies Steinhubl S, Berger P, Tift Mann III J et al. JAMA. 2002;Vol 288,No 19:2411-2420.

Effect of Timing of Loading Dose: 28 Day Endpoint - Death, MI, UTVR Events (%) PT-Clopidogrel* No-PT* N PT-Clopidogrel Better No-PT Better 3 to <6 hrs 7.9 7.0 893 6 to 24 hr 5.8 9.4 851 RRR -13.4 P=NS RRR 38.6 P=0.05 Overall CREDO Results RRR 18.5 P=0.23 PT= Pre-treatment * Plus ASA and other standard therapies Steinhubl S, Berger P, Tift Mann III J et al. JAMA. 2002;Vol 288,No 19:2411-2420. 0.4 0.6 0.8 1.0 1.2 Hazard ratio (95% CI)

From: Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis JAMA. 2012;308(23):2507-2516. doi:10.1001/jama.2012.50788 Date of download: 5/10/2014 Copyright 2014 American Medical Association. All rights reserved.

From: Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis JAMA. 2012;308(23):2507-2516. doi:10.1001/jama.2012.50788 Clopidogrel előkezelés nem káros!!! Date of download: 5/10/2014 Copyright 2014 American Medical Association. All rights reserved.

TAGG előkezelés De mi a helyzet az előkezeléssel? Stabil angina pectoris ACS

Synergistic Mode of Action with Clopidogrel and ASA 1 CLOPIDOGREL C ADP ADP GPllb/llla (Fibrinogen receptor) Activation Collagen thrombin TXA 2 ASA COX TXA 2 COX (cyclo-oxygenase) ADP (adenosine diphosphate) TXA 2 (thromboxane A 2 ) 1. Schafer AI. Am J Med 1996; 101: 199 209.

CLOPIDOGREL ACS-ben - dózis OASIS-7 36

CLOPIDOGREL ACS-ben - dózis OASIS-7 37 clopidogrel ACS-ben PCI esetén: Telítő dózis 600 mg Fenntartó dózis: min. egy hétig 150 mg

Farmakokinetika a háttér 85%: Inaktiv Metabolit Esterase hce1 (főleg hepatikus) hce1 Clopidogrel Prodrug HEPATIKUS CYPs (2C19, 1A2, 2B6) Közbülső (inaktív) metabolit HEPATIKUS CYP: (3A, 2B6, 2C19, 2C9) Aktiv metabolit Kurihara A et al. Drug Metab Rev 2005;37(S2):99 Tang M et.al. J Pharmacol Exp Ther 2006;319:1467-1476 Farid NA et al. Drug Metab Dispos 2007;35:1096-1104 Rehmel JLF et al. Drug Metab Dispos 2006;34:600-607 Williams ET et al. Drug Metab Dispos 2008;36:1227-1232

Farmakokinetika a háttér 85%: Inaktiv Metabolit Esterase hce1 (főleg hepatikus) hce1 Clopidogrel (2.gen) Prodrug HEPATIKUS CYPs (2C19, 1A2, 2B6) Prasugrel (3.gen) Prodrug Esterase hce2 (főleg INTESTINALIS) Közbülső (inaktív) metabolit Közbülső (inaktív) metabolit HEPATIKUS CYP: (3A, 2B6, 2C19, 2C9) INTESTINALIS CYP (3A, 2C9, 2C19) HEPATIKUS CYP: (3A, 2B6, 2C9, 2C19) Aktiv metabolit Kurihara A et al. Drug Metab Rev 2005;37(S2):99 Tang M et.al. J Pharmacol Exp Ther 2006;319:1467-1476 Aktiv metabolit Farid NA et al. Drug Metab Dispos 2007;35:1096-1104 Rehmel JLF et al. Drug Metab Dispos 2006;34:600-607 Williams ET et al. Drug Metab Dispos 2008;36:1227-1232

TAGG % (20 mm ADP) Thrombocyta aggregáció gátlás egészséges önkénteseken (F.I) Telítő dózis Fenntartó dózis Idő 100 90 80 70 60 50 40 30 20 10 0-10 * * * * * * * 0.25 0.5 1 2 4 6 * * * * * * * p<0.001 Prasugrel vs Clopidogrel p<0.05 Clopidogrel 600 mg vs 300 mg p<0.001 Clopidogrel 600 mg vs 300 mg Pre-dose IPA 2 3 4 5 6 7 8 9 1 nap, órák Napok Clopidogrel 600 mg/75 mg Clopidogrel 300 mg/75 mg Prasugrel 60 mg/10 mg TAGG =Thrombocyta aggregáció gátlás; ADP=Adenemsine diphosphate Payne CD et al. J Cardiovasc Pharmacol 2007;50(5):555-562

CV halál, MI, Stroke (%) TRITON-TIMI 38 primer végpont 15 P=0.002 Clopidogrel 12.1 10 5 Prasugrel P=0.03 P<0.001 P=0.01 HR 0.81 (0.73-0.90) NNT= 46 9.9 0 0 30 60 90 180 270 360 450 Wiviott et al. New Engl J Med 2007;357:2001-2015 Napok

TRITON-TIMI 38: Primer végpont: az IDŐPONT! CV halál/mi/stroke (%) 8 6.9 6 Clopidogrel 5.6 Clopidogrel 5.6 4 Prasugrel 4.7 Prasugrel 2 0 HR 0.82 (0.71-0.96) P=0.01 RRR 18% ARR 0.9% 0 1 2 3 3 30 90 180 270 360 450 Napok ARR=Absolute Risk Reduction; CV=Cardiovascular; HR=Hazard Ratio; MI=Myocardial Infarction; RRR=Relative Risk Reduction HR 0.80 (0.70-0.93) P=0.003 RRR 20% ARR 1.3% Wiviott SD et al. New Engl J Med 2007;357:2001-2015

Stent Thrombosis (%) TRITON-TIMI 38: STENTTHROMBOSIS 3 2 Stent szám/ Index PCI n=12,844 Clopidogrel 2.35 1 Prasugrel 1.13 HR 0.48 (0.36-0.64) P<0.0001 RRR 52% 0 NNT=77 ARR 1.22% 0 30 60 90 180 270 360 450 Napok ARC=Academic Research Consortium; ARR=Absolute Risk Reduction; HR=Hazard Ratio; NNT=Number Needed to Treat; PCI=Percutaneous Coronary Intervention; RRR=Relative Risk Reduction Wiviott SD et al. Lancet 2008;371:1353-1363

% betegek TRITON-TIMI 38: STENTTHROMBOSIS 2.5 2 1.5 1 0.5 KORAI Stent Thrombosis Pras N=6,422; Clop N=6,422 Clopidogrel Prasugrel 1.56% HR 0.41 (0.29-0.59) p<0.0001 RRR 59% 0.64% KÉSŐI Stent Thrombosis Pras N=6,271; Clop N=6,250 Clopidogrel Prasugrel HR 0.60 (0.37-0.97) p=0.03 RRR 40% 0.82% 0.49% 0 0 5 10 15 20 25 30 30 90 150 210 270 330 390 450 Napok ARC=Academic Research Consortium; HR=Hazard ratio; RRR=Relative risk reduction Wiviott SD et al. Lancet 2008;371:1353-1363

K-M estimated rate (% per year) All cause mortality STEMI 7 6 Clopidogrel 6.0 5 4 Ticagrelor 4.9 3 2 1 HR 0.82 (95% CI = 0.68 0.99), p=0.04 No. at risk Ticagrelor Clopidogrel 0 01 2 3 4 5 6 7 8 9 10 11 12 Months 4,2014,005 3,962 3,876 3,150 2,413 1,993 4,2294,029 3,989 3,912 3,195 2,471 1,980

Stent thrombosis (as per ARC definitions)* STEMI Ticagrelor (n=4,201) Clopidogrel (n=4,229) HR for ticagrelor (95% CI) p- value Definite Probable or definite Possible, probable, or definite 1.6 2.5 3.2 2.5 3.6 4.4 0.61 (0.42 0.87) 0.69 (0.52 0.92) 0.73 (0.56 0.94) 0.01 0.01 0.02 Time-at-risk is calculated from the date of first stent insertion in the study or date of randomization *Cutlip et. al., Circulation. 2007;115:2344 2351 By univariate Cox model

K-M estimated rate (% per year) Primary safety event: major bleeding STEMI 10 8 6 Clopidogrel Ticagrelor 9.3 9.0 4 2 0 HR 0.96 (95% CI = 0.83 1.12), p=0.63 No. at risk Ticagrelor Clopidogrel 01 2 3 4 5 6 7 8 9 10 11 12 Months 4,1653,431 3,254 3,137 2,440 1,786 1,640 4,1813,430 3,297 3,159 2,441 1,804 1,635

(%) TRITON-TIMI 38: Egyéb vérzés (15 hónap) (n=6,716) (n=6,741) Odds Ratio 4.73 P<0.001 13.4% 24/179 P=0.002 5.0% 3.8% n=303 n=231 P<0.001 3.0% n=182 4.0% n=244 3.2% 6/189 TIMI Major és Minor Transfusiot igénylő CABG-hez kapcsolódó Major vérzés ACS=Acute Coronary Syndrome; CABG=Coronary Artery Bypass Graft surgery; HR=Hazard Ratio; TIMI=Thrombolysis In Myocardial Infarction Wiviott SD et al. New Engl J Med 2007;357:2001-2015

ACCOAST design NSTEMI + Troponin 1.5 times ULN local lab value Clopidogrel naive or on long term clopidogrel 75 mg Randomize 1:1 Double-blind n~4100 (event driven) Prasugrel 30 mg Placebo CABG or Medical Management (no more prasugrel) Coronary Angiography Prasugrel 30 mg Coronary Angiography Prasugrel 60 mg CABG or Medical Management (no prasugrel) PCI PCI Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days 1 Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa bailout, at 7 days Montalescot G et al. Am Heart J 2011;161:650-656

Endpoint (%) 1 Efficacy End Point @ 7 + 30 days (All Patients) 15 Pre-treatment 10.0 CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout Pre-treatment 10.8 10 No Pre-treatment 9.8 No Pre-treatment 10.8 5 Hazard Ratio, 1.02 (95% 0.84, 1.25) P=0.81 Hazard Ratio, 0.997 (95% 0.83, 1.20) P=0.98 No. at Risk, Primary Efficacy End Point: No pre-treatment Pre-treatment 0 0 5 10 15 20 25 30 1996 2037 1788 1821 Days From First Dose 1775 1809 1769 1802 1762 1797 1752 1791 1621 1616

Endpoint (%) All TIMI (CABG or non-cabg) Major Bleeding (All Treated patients) 5 4 Hazard Ratio, 1.90 (95% 1.19, 3.02) P=0.006 Hazard Ratio, 1.97 (95% 1.26, 3.08) P=0.002 3 Pre-treatment 2.6 Pre-treatment 2.9 2 All TIMI Major Bleeding 1 0 No Pre-treatment 1.4 No Pre-treatment 1.5 No. at Risk, All TIMI Major Bleeding: No pre-treatment Pre-treatment 0 5 10 15 20 25 30 1996 2037 1947 1972 Days From First Dose 1328 1339 1297 1310 1288 1299 1284 1297 1263 1280

Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery G. Montalescot, A.W. van t Hof, F. Lapostolle, J Silvain, J.F. Lassen, L. Bolognese, W.J. Cantor, A. Cequier, M. Chettibi, S.G. Goodman, C.J. Hammett, K. Huber, M. Janzon, B. Merkely, R.F. Storey, U. Zeymer, O. Stibbe, P. Ecollan, W.M.J.M. Heutz, E. Swahn, J.P. Collet, F.F. Willems, C. Baradat, M. Licour, A. Tsatsaris, E. Vicaut, C.W. Hamm, for the ATLANTIC investigators G. Montalescot, COI are available at www.action-coeur.org

Study population and design

Pre-specified clinical 2 endpoints Composite of death, MI, stent thrombosis, stroke or urgent revascularization at 30 days Definite stent thrombosis at 30 days Thrombotic bailout with GPIIb/IIIa inhibitors

1 st Co-primary endpoint No ST-segment resolution ( 70%)

2 nd Co-primary endpoint No TIMI 3 flow in infarct-related artery

Definite stent thrombosis up to 10 days

Definite stent thrombosis up to 30 days

Clinical endpoints at 30 days Values are % Odds ratio (95% CI) p-value Death (all-cause) MI Stroke TIA Urgent coronary revascularization Bail-out GP IIb/IIIa inhibitors 1.68 (0.94, 3.01) 0.08 0.73 (0.28, 1.94) 0.53 2.11 (0.39, 11.53) 0.39 Not estimable 0.66 (0.21, 2.01) 0.46 0.80 (0.59, 1.10) 0.17

Kettős TAGG meddig? Alap: 1 év, de alacsony vérzéses és magas ischaemias rizikó esetén egy éven túl is érdemes ticagrelor-lal (2x60 mg) 60

Individualizing Treatment Duration of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: An Analysis from the DAPT Study Robert W. Yeh, Eric A. Secemsky, Dean J. Kereiakes, Sharon-Lise T. Normand, Anthony H. Gershlick, David J. Cohen, John A. Spertus, P. Gabriel Steg, Donald E. Cutlip, Michael J. Rinaldi, Edoardo Camenzind, William Wijns, Patricia K. Apruzzese, Yang Song, Joseph M. Massaro, and Laura Mauri, for the Dual Antiplatelet Therapy (DAPT) Study Investigators

Design Randomiza on Primary Analysis Period Study Drug Treatment Ends 12-Month Observa onal Period: Open-Label Thienopyridine + Aspirin Required Thienopyridine + Aspirin Placebo + Aspirin 3-Month Observa onal Period: Off Thienopyridine, On Aspirin 0 (mos) 12 30 33 Inclusion: FDA-approved DES or BMS, candidates for thienopyridine Excluded: Oral anticoagulant therapy; life expectancy < 3y Randomized: Free from MI, stroke, repeat revascularization, moderate/severe bleeding, and adherent with therapy at 12 months Mauri, Kereiakes et al. AHJ. 2010;160(6): 1035-41. ClinicalTrials.gov number NCT00977938 62

ESC 2015 NSTE-ACS Guideline Kettős TAGG meddig www.daptstudy.org 63

Cumulative Incidence of GUSTO Moderate/ Severe Bleed Cumulative Incidence of ST/MI Cumulative Incidence of MACCE Continued Thienopyridine vs. Placebo DAPT Score <2 (Low); N=5731 Myocardial Infarction or Stent Thrombosis 10% 8% Continued Thienopyridine Placebo Death, MI, or Stroke (MACCE) 10% 8% Continued Thienopyridine Placebo 6% 6% 4% 1.7% vs. 2.3% P=0.07 4% 3.7% vs. 3.8% P=0.73 2% 2% 0% 12 15 18 21 24 27 30 GUSTO Moderate/ Severe Bleeding Months After Enrollment 10% 8% 6% 4% 2% 3.0% vs. 1.4% P<0.001 0% Continued Thienopyridine Placebo 12 15 18 21 24 27 30 Months After Enrollment 0% 12 15 18 21 24 27 30 Months After Enrollment 64

Cumulative Incidence of GUSTO Moderate/ Severe Bleed Cumulative Incidence of ST/MI Cumulative Incidence of MACCE Continued Thienopyridine vs. Placebo DAPT Score 2 (High); N=5917 Myocardial Infarction or Stent Thrombosis 10% 8% Continued Thienopyridine Placebo Death, MI or Stroke (MACCE) 10% 8% Continued Thienopyridine Placebo 6% 4% 2.7% vs. 5.7% P<0.001 6% 4% 4.9% vs. 7.6% P<0.001 2% 2% 0% 12 15 18 21 24 27 30 GUSTO Moderate/ Severe Bleeding Months After Enrollment 10% 8% 6% 4% 2% 1.8% vs. 1.4% P=0.26 0% Continued Thienopyridine Placebo 12 15 18 21 24 27 30 Months After Enrollment 0% 12 15 18 21 24 27 30 Months After Enrollment 65

De meddig?? Kettős TAGG kezelés felfüggesztése ACS-ben végzett PCI után 30 napon belül 30 nap 6 hónap 6 hónap egy év egy év után

Kettős TAGG kezelés felfüggesztése ACS-ben végzett PCI után 30 napon belül KATASZTRÓFA!!!! Stent-thrombosis valószínűsége 30X (=AMI) Magas thromboticus Stabil rizikó AP NSTE-ACS esetén rövid felezési STEMI idejű GPIIb/IIIa BMS bl. (tirofiban, 0-0,5 % eptifibatide) 1,4-1,6 % a műtétig 2,9 % (ACBG) DES 0,3-0,4 % 1,2-1,9 % 3,1 % (ha nem életveszélyes vérzés miatt kell felfüggeszteni) Cook, Windecker. Circulation 2009;119:657-9

Kettős TAGG kezelés elhagyása DES esetében 6 hónapos kezelés utáni elhagyás esetében 1. generációs DES-ek!

Kettős TAGG kezelés elhagyása DES esetében Új generációs DES-ek!!!!

Kettős TAGG kezelés elhagyása DES esetében PRODIGY 6 hónap elég????

Kettős TAGG kezelés elhagyása DES esetében 12 hónap elég????

DAPT SPECIÁLIS HELYZETEKBEN 73

DAPT SPECIÁLIS HELYZETEKBEN 74

TAGG MÉRÉS? 75

TAGG MÉRÉS? 76

TAGG MÉRÉS? 77

DAPT + AC kezelés Hármas kezelés időtartamát minimalizálni kell a vérzéses rizikó csökkentése érdekében (WOEST study!)

WOEST STUDY 573 beteg OAC indikált (PF vagy MB) 1:1 randomizáció: PCI, majd OAC + clopidogrel OAC + ASA + clopidogrel Primer végpont: TIMI major vérzés Szekunder végpont: Halál + célér revasc. + AMI + stent thrombosis primer + szekunder végpont

WOEST STUDY Cumulative incidence of bleeding Primary Endpoint: Total number of TIMI bleeding events 50 % Triple therapy group Double therapy group 44.9% 40 % 30 % 20 % 19.5% 10 % 0 % p<0.001 HR=0.36 95%CI[0.26-0.50] 0 30 60 90 120 180 270 365 Days n at risk: 284 210 194 186 181 173 159 140 279 253 244 241 241 236 226 208

WOEST STUDY Cumulative incidence Secondary Endpoint (Death, MI,TVR, Stroke, ST) 20 % Triple therapy group Double therapy group 17.7% 15 % 11.3% 10 % 5 % 0 % p=0.025 HR=0.60 95%CI[0.38-0.94] 0 30 60 90 120 180 270 365 Days n at risk: 284 272 270 266 261 252 242 223 279 276 273 270 266 263 258 234

WOEST STUDY Cumulative incidence of death 7.5 % All-Cause Mortality Triple therapy group Double therapy group 6.4% 5 % HR=0.39 95%CI[0.16-0.93] p=0.027 2.5 % 2.6% 0 % 0 30 60 90 120 180 270 365 Days n at risk: 284 281 280 280 279 277 270 252 279 278 276 276 276 275 274 256

PF + PCI: NOAC + TAGG monoth. vs. triple th. PIONEER apixaban REDUAL dabigatran 110 (!!) /150 mg AUGUSTUS ENTRUST-AF-PCI 86

Megválaszolatlan kérdések: Prehospitalis prasugrel kezelés STEMI-ben (lsd. ATLANTIC ticagrelor ) Ticagrelor előkezelés NSTE-ACS-ben Stabil coronaria betegség és PCI esetén potens DAPT telítés (Ticagrelor verus clopidogrel ( ALPHEUS) és a SASSICAIA Rövid távú DAPT és hosszú ticagrelor monoterápia - GLOBAL LEADERS (biolimus-eluting stent) és a TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) 87

ÖSSZEFOGLALÁS Előkezelés: SCAD: lehet ACS: kell ASA + clopidogrel Kettős TAGG PCI után (DES) Min. 3 hó de opt. 6 hó ACS: 12 hónap Prasugrel vagy Ticagrelor Hármas kezelés: Ischaemias és vérzéses rizikótól függ VKA/NOAC+ASA+clopidogrel Amikor ketten maradnak (AC+TAG): Ha dabigatran, 2x150 mg+ clopidogrel 88