MANAGEMENT AKUTES KORONARSYNDROM: RISIKOSTRATIFIZIERUNG UND THERAPIE. Peter Wenaweser Universitätsklinik für Kardiologie

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1 MANAGEMENT AKUTES KORONARSYNDROM: RISIKOSTRATIFIZIERUNG UND THERAPIE Peter Wenaweser Universitätsklinik für Kardiologie

2 Scientific Advances & Cardiovascular Mortality 1950 to 2010 Nabel EM and Braunwald E. N Engl J Med 2012;366:54-63

3 Coronary Artery Disease and Mortality Boersma E et al. Lancet 2003;361:847-58

4 Temporal Trends in the Treatment of Myocardial Infarction in Switzerland AMIS Plus Registry, Radovanovic et al, 2012

5 Universitätsklinik für Kardiologie Reduktion der Mortalität nach Myokardinfarkt % Monitoring Defibrillation OAK Thrombolyse innerhalb der ersten 30 Tage Aspirin 12 8 Primäre PCI Clopidogrel DES Prasugrel Ticagrelor Pell et al Modan et al Tonascia et al Tonascia et al Modan et al GISSI GISSI ISIS-2 Grines et al Keeley et al Grines et al CADILLAC CLARITY-TIMI28 HORIZONS AMI TRITON-TIMI 38 PLATO COMFORTABLE Fortschritte in der Behandlung des Akuten Myokardinfarktes / Thomas Pilgrim 14

6 Symptoms suggestive of ACS STEMI NSTE-ACS UA ECG Labs

7 Risk and timing of Death among Patients with Stable Coronary Artery Disease, NSTE-ACS, and STEMI Pilgrim T et al, submitted Individual patient data pooled analysis of 6740 patients from 4 all-comers trials SIRTAX, LEADERS, RESOLUTE, PRODIGY STEMI NSTE-ACS Stable CAD

8 Risk and timing of Death among Patients with Stable Coronary Artery Disease, NSTE-ACS, and STEMI Individual patient data pooled analysis of 6740 patients from 4 all-comers trials SIRTAX, LEADERS, RESOLUTE, PRODIGY STEMI versus Stable CAD 0-30 days: HR 6.85 (95% CI ) All Cause Death (Landmark at 30 days) Landmark- Analysis Pilgrim T et al, submitted STEMI STEMI versus Stable CAD days: HR 1.07 (95% CI ) NSTE-ACS 4 STEMI (%) 3 Stable CAD HR (95%CI); p-value STEMI vs Stable CAD 0-30d: 6.85 ( ); d: 1.07 ( ); NSTE-ACS vs Stable CAD 0-30d: 2.22 ( ); d: 1.41 ( ); p-interaction = Days since index procedure

9 Risk and timing of Death among Patients with Stable Coronary Artery Disease, NSTE-ACS, and STEMI Individual patient data pooled analysis of 6740 patients from 4 all-comers trials SIRTAX, LEADERS, RESOLUTE, PRODIGY NSTE-ACS versus Stable CAD 0-30 days: HR 2.22 (95% CI ) All Cause Death (Landmark at 30 days) Landmark- Analysis Pilgrim T et al, submitted NSTE-ACS NSTE-ACS versus Stable CAD days: HR 1.41 (95% CI ) NSTE-ACS 4 STEMI (%) 3 Stable CAD HR (95%CI); p-value STEMI vs Stable CAD 0-30d: 6.85 ( ); d: 1.07 ( ); NSTE-ACS vs Stable CAD 0-30d: 2.22 ( ); d: 1.41 ( ); p-interaction = Days since index procedure

10 Risk Stratification NSTE-ACS ESC Guidelines NSTE-ACS, 2011 High-Risk Criteria

11 Risk Stratification NSTE-ACS ESC Guidelines NSTE-ACS, 2011 High-Risk Criteria

12 Risk Stratification GRACE Risk Score In-hospital Mortality and Mortality at 6 Months

13 Risk Stratification High-Sensitivity Troponin Assays

14 Rates of Cardiac Death or Myocardial infarction Stratified by Baseline Cardiac Troponin Levels Apple et al. Clin Chem 2009 Even patients with small ctni elevation had a significantly increased risk of death or MI compared with patients with normal ctni concentrations

15 Risk Stratification NSTE-ACS ESC Guidelines NSTE-ACS, 2011 High-Risk Criteria

16 Stellenwert triple-roule-out CT? Diagnostic strategies in stable patients according to pretest probability of disease Stefanini G G, and Windecker S Circulation. 2015;131:

17 2011 ESC Guidelines for NSTE-ACS Hamm C et al. Eur Heart J 2011 ECG Recommendation for Risk Stratification Biomarkers Stress test Coronary CT

18 Targets for Platelet Inhibition

19 CURRENT OASIS 7 Acute Coronary Syndromes Aspirin Double Dosage Mehta SR et al. N Engl J Med 2010;363: Primary outcome: CV death, MI or stroke at 30 days Aspirin high dose ( mg) versus low dose ( mg) p = ns QuickTime are decompressor needed to and see athis picture. Major GI Bleeding: 0.4% (high dose) vs 0.2% (low dose), P=0.04

20 Clopidogrel ADP P2Y12-Inhibitoren Prasugrel Elinogrel Ticagrelor Cangrelor

21 Primary outcome PCI Population Mehta SR et al Lancet 2010;376: Definite/probable Stent Thrombosis QuickTime and a decompressor are needed to see this picture.

22 Universitätsklinik für Kardiologie Neue Thombozytenaggregationshemmer Monitoring Defibrillation OAK Thrombolyse, Aspirin Primäre PCI Clopidogrel Prasugrel Ticagrelor Pell et al Modan et al Tonascia et al Tonascia et al Modan et al GISSI GISSI ISIS-2 Grines et al Keeley et al Grines et al CADILLAC CLARITY-TIMI28 HORIZONS AMI TRITON-TIMI 38 PLATO COMFORTABLE Fortschritte in der Behandlung des Akuten Myokardinfarktes / Thomas Pilgrim 47

23 Universitätsklinik für Kardiologie Nachteile des Clopidogrels Schömig A. N Engl J Med 2009;361: Verzögerter Wirkungseintritt 2. Interindividuelle Variabilität der Thrombozytenaggregationshemmung 3. Irreversible Wirkung Fortschritte in der Behandlung des Akuten Myokardinfarktes / Thomas Pilgrim 48

24 Universitätsklinik für Kardiologie Wirkungsmechanismus Schömig A. N Engl J Med 2009;361: Fortschritte in der Behandlung des Akuten Myokardinfarktes / Thomas Pilgrim 53

25 Triton TIMI 38 Prasugrel vs. Clopidogrel Wiviott SD et al. N Engl J Med 2007;357: Primary Endpoint (%) HR 0.77 P= Primary Endpoint: CV Death, MI, Stroke HR 0.80 P= Clopidogrel Prasugrel 12.1 (781) 9.9 (643) HR 0.81 ( ) P= NNT= 46 0 ITT= 13,608 LTFU = 14 (0.1%) Days

26 Ticagrelor versus Clopidogrel in ACS Wallentin L al. N Engl J Med 2009;361: Primary Endpoint: CV Death, MI or Stroke 11.7% 9.8% p= HR 0.84 (95% CI ) RRR = 16%, ARR = 1.87%, NNT = 54

27 Antiplatelet Agents for Secondary Prevention in ACS Pilgrim T and Windecker S, Heart. 2014;100(22): Prasugrel good in diabetes, but not so good in the elderly Conservative Management - Prasugrel has similar efficacy as Clopidogrel - Ticagrelor reduces mortality as compared to Clopidogrel, but increases rates of bleeding PCI STEMI - Both Prasugrel and Ticagrelor reduce ischemic endpoints compared to Clopidogrel - Ticagrelor reduces mortality compared to Clopidogrel - Prasugrel reduces ST compared to Clopidogrel - Ticagrelor increases risk of stroke compared to clopidogrel

28 Recommendations for Antiplatelet Therapy in NSTE-ACS Antiplatelet Therapy Duration - Aspirin mg should be given to all patients without contraindications and continued daily long-term (75-100mg) - ADP P2Y12 inhibitor should be added to aspirin asap and maintained over 12 months - Withdrawal of P2Y12 inhibitors within 12 months is discouraged unless clinically indicated P2Y12 Inhibitor Selection - Ticagrelor (180mg LD, 90mg bid) for all patients with moderate-to-high risk (>troponin), regardless initial treatment strategy - Prasugrel (60mg LD, 10mg od) for P2Y12 patients with known coronary anatomy proceeding to PCI (unless high risk of life-threatening bleeding) - Clopidogrel (300mg LD, 75mg od) for patients who cannot receive ticagrelor or prasugrel I A I A I C I B I B I A

29 Antithrombin Agents in Acute Coronary Syndromes

30 Recommendations for Antithrombotic Therapy in NSTE-ACS

31 Acute Myocardial Infarction Thrombolysis vs. Primary PCI: Short-Term Results Keeley EC et al. Lancet 2003;361:13 P< lives and 44 MI`s saved and 11 strokes avoided for every 1000 pts treated with primary PCI instead of thrombolysis 43% Death, MI, Stroke 22% 57% P= P< Meta-Analysis -N=7739 patients -23 randomized trials -8x:streptokinase vs PTCA -15x: tpa vs PTCA 50% P< % P< Death Reinfarction Stroke ICH 1 PCI Thrombolysis

32 Universitätsklinik für Kardiologie Reperfusionszeit und Mortalitätsreduktion Gersh B et al. JAMA 2005;293: pro 15 Minuten 6 Leben/1000 Patienten Fortschritte in der Behandlung des Akuten Myokardinfarktes / Thomas Pilgrim 83

33 ESC STEMI Management Guidelines Steg P et al. Eur Heart J 2012

34 Risk Stratification Use of DES Acute Coronary Syndromes Antiplatelet Therapy Invasive Management Antithrombotic Therapy

35 Universitätsklinik für Kardiologie Koronarstents BMS: Bare-metal stents DES: Drug-eluting stents Early Generation DES Newer Generation DES Stefanini GG et al, N Engl J Med 2013;368: ACS, Review-Kurs 2015, Wenaweser 91

36 Universitätsklinik für Kardiologie NEW GENERATION DES VERSUS BMS IN STEMI EXAMINATION Sabaté M et al. Lancet 2012; 380: COMFORTABLE Räber L et al. JAMA 2012;308: Death, MI, any Revasc Cardiac Death, TV-MI, ci-tlr ACS, Review-Kurs 2015, Wenaweser 96

37 Universitätsklinik für Kardiologie Risiko einer Stentthrombose in Abhängigkeit der Zeit «early» «late» «very-late» Risiko BMS 0.5%/Jahr 0.5% 0.1%/Jahr Stefanini G et al. Lancet 2011;378: Wenaweser P et al. J Am Coll Cardiol 2008;52: Monat 12 Monate Zeitachse ACS, Review-Kurs 2015, Wenaweser 97

38 Take Home Message Risk Stratification NSTEMI: GRACE risk score Use of DES - Newer generation DES superior to BMS Acute Coronary Syndromes Antiplatelet Therapy - Ticagrelor - Prasugrel Invasive Management - NSTEMI: urgent, early, 72 h Antithrombotic Therapy - Fondaparinux - Bivalirudin

39 MANAGEMENT AKUTES KORONARSYNDROM: RISIKOSTRATIFIZIERUNG UND THERAPIE Danke für die Aufmerksamkeit Peter Wenaweser Universitätsklinik für Kardiologie