On admission Acute extensive anterior STEMI

Transcription

1 Mr B 52 years old male Smoker No prior known CAD Presents with 1 hour intermittent crushing retrosternal chest pain Transferred by MICU directly to CCU (ASA, Heparin)

2 On admission Intense pain, diaphoretic Pulse 90, BP 140/90 ECG- ST elevation V1-6, I, avl Dg- Acute extensive anterior STEMI Referred directly for PPCI While on the cath. Lab. the pain abates and ST elevation resolves on monitor.

3 ECG

4 On admission Intense pain, diaphoretic Pulse 90, BP 140/90 ECG- ST elevation V1-6, I, avl Dg- Acute extensive anterior STEMI (prasugrel) Referred directly for PPCI While on the cath. Lab. the pain abates and ST elevation resolves on monitor.

5 Angiogram

6 Angiogram

7 On admission Intense pain, diaphoretic Pulse 90, BP 140/90 ECG- ST elevation V1-6, I, avl Dg- Acute extensive anterior STEMI Referred directly for PPCI While on the cath. Lab. the pain abates and ST elevation resolves on monitor.

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9 Objectives How important is to achieve effective platelet PPCI? Should DAPT be given ASAP in STEMI Pt s undergoing PPCI (FMC)? If yes, What DAPT should be given? What should be done if a patient on DAPT required immediate CABG? Non urgent CABG (invasive procedure)?

10 Objectives How important is to achieve effective platelet PPCI? Should DAPT be given ASAP in STEMI Pt s undergoing PPCI (FMC)? If yes, What DAPT should be given? What should be done if a patient on DAPT required immediate CABG? Non urgent CABG (invasive procedure)?

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12 Systemic review ( 26 RC studies) Unselected STEMI pts undergoing PPCI N=8429 Clopidogrel Pre-treatment )N= 4114) No Clopidogrel Pretreatment (N= 4315) Vlaar et al circulation; 118:

13 Effect of Clopidogrel Pre-treatment on Early Reperfusion and Clinical Outcome TIMI flow 2/3 on initial CAG P< % 25.8% 2 2.4% d Mortality P< % Death and/or Re-infarction P< % 6.3% Clopidogrel pre-treatment No Clopidogrel pre-treatment

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15 SCAAR registry 1 st STEMI undergoing PPCI N=13,847 Upstream clopidogrel (prior to cath. lab.) N=9813 (71%) No upstream clopidogrel N=4034 (29%) Koul et al. Eur Heart J 2011; 32:

16 Death and\or Reinfarction Mortality Koul et al. Eur Heart J 2011; 32: Effect of Clopidogrel Up-Stream on Mortality and Re-infarction* * Propensity Score-Adjusted Incidence OR=0.82(95%CI ) OR=0.76(95%CI ) Clopidogrel upstream No clopidogrel Upstream

17 Objectives How important is to achieve effective platelet PPCI? Should DAPT be given ASAP in STEMI Pt s undergoing PPCI (FMC)? If yes, What DAPT should be given? What should be done if a patient on DAPT required immediate CABG? Non urgent CABG (invasive procedure)?

18 Inhibition of Platelet Aggregation (%) Prasugrel vs. Clopidogrel Loading Dose: Higher IPA During Loading Dose Maintenance Doses Pras 60 mg * * * * * * Clop 600 mg! Pras 10 mg * * * * * * * Clop 75 mg 40! Clop 75 mg Clop 300 mg mean ± SEM 20 μm ADP * p<0.001 vs. Clop 300 mg or 600 mg LD p<0.001 vs. Clop 300! p<0.05 vs. Clop 300 p<0.05 vs Clop 300/75 Time Hours Days

19 P< for all AZD6140 groups vs clopidogrel at 4 h IPA (%) Mean ± SEM P< for all AZD6140 groups vs clopidogrel at 4 h IPA on Day 1 Clopidogrel Naive Patients 100 Final Extent Time, h Ticagrelor 90 mg Ticagrelor 180 mg Ticagrelor 270 mg CLOP 300 mg

20 ADP-platelet aggregation at PPCI )% ( Platelet PPCI According to the Time Elapsed from Thienopyridine Loading to PPCI P= Clopidogrel Prasugrel Time from 50 thienopyridine loading to 100 PPCI (min) 150 Clopidogrel Prasugrel Clopidogrel Prasugrel Matetzky et al. ACC 2012

21 ADP Induced Aggregation (%) ADP Induced Platelet Aggregation 100 P= 0.8 P= P< Clopidogrel Prasugrel 0 Baseline Baseline PPCI PPCI 3rd Day 3rd Day Matetzky et al. ACC 2012

22 Indices of Myocardial Reperfusion in STEMI Patients Undergoing PPCI P= % P= % 71% Clopidogrel Prasugrel % TMP 2\3 Early STR Matetzky et al. ACC 2012

23 RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study Parodi G. JACC 2013 (Apr) 16 ;61(15):1601-6

24 Kinetics of Platelet Inhibition Over Time Residual platelet reactivity values assessed by platelet reactivity units VerifyNow at baseline and.2, 4, 8, and 12 h after drug loading *p < 0.01 versus Ticagrelor. p < 0.01 versus baseline, p < 0.01 versus 2 h. Parodi G. JACC 2013 (Apr) 16 ;61(15):1601-6

25 Inhibition of Platelet Aggregation by VerifyNow at 2, 4, 8, and 12 h after drug loading dose P < 0.01 Parodi G. JACC 2013 (Apr) 16 ;61(15):1601-6

26 Objectives How important is to achieve effective platelet PPCI? Should DAPT be given ASAP in STEMI Pt s undergoing PPCI (FMC)? If yes, What DAPT should be given? What should be done if a patient on DAPT required immediate CABG? Non urgent CABG (invasive procedure)?

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28 37 Price M et al. JACC 2012 June;59 :

29 Proportion of Pts Returning to Baseline Reactivity 39 Price M et al. JACC 2012 June;59 :

30 Thienopyridines bind covalently (irreversibly) to P2Y12 ADP binding site, rendering the receptors permanently inactivated Ticagrelor binds directly to P2Y 12 receptors and reversibly interacts with the receptor, to prevent platelet activation and aggregation Thienopyridines-Irreversible inhibition Ticagrelor-Reversible inhibition P Savi, et al. Proc Natl Acad Sci USA 2006; 103:

31 Vilahur et al J. Thromb. Haemostasis 2007;5:

32 Vilahur et al J. Thromb. Haemostasis 2007;5:

33 Vilahur et al J. Thromb. Haemostasis 2007;5:

34 Vilahur et al J. Thromb. Haemostasis 2007;5:

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36 51

37 Thienopyridines bind covalently (irreversibly) to P2Y12 ADP binding site, rendering the receptors permanently inactivated Ticagrelor binds directly to P2Y 12 receptors and reversibly interacts with the receptor, to prevent platelet activation and aggregation Thienopyridines-Irreversible inhibition Ticagrelor-Reversible inhibition P Savi, et al. Proc Natl Acad Sci USA 2006; 103:

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39 IPA % * * * * * * * * Ticagrelor 180mg LD / 90 mg bd (n=54) Clopidogrel 600mg LD / 75 mg od (n=50) * Gurbel PA et al. Circulation weeks Onset Maintenance Offset Time (hours)

40 What Can Be Done Within the First 120 hr?

41 Objectives How important is to achieve effective platelet PPCI? Should DAPT be given ASAP in STEMI Pt s undergoing PPCI (FMC)? If yes, What DAPT should be given? What should be done if a patient on DAPT required immediate CABG? Non urgent CABG (invasive procedure)?

42 Proportion of Pts Returning to Baseline Reactivity 8 Units of PLT Price M et al. JACC 2012 June;59 :

43 Proportion of Pts Returning to Baseline Reactivity Price M et al. JACC 2012 June;59 :

44 IPA % * * * * * * * * Ticagrelor 180mg LD / 90 mg bd (n=54) Clopidogrel 600mg LD / 75 mg od (n=50) * Gurbel PA et al. Circulation weeks Onset Maintenance Offset Time (hours)

45 Thank You

46 18,624 patients randomized CABG CABG in 1,899 patients during the course of the study CABG in 1,261 patients with last intake of study drug 7 days prior to surgery: 632 patients treated with ticagrelor 629 patients treated with clopidogrel Held et al. JACC 2011; 57(6):

47 K-M estimated rate (%) Time from study entry to first CABG surgery (total PLATO population) CABG HR: 0.96 (95% CI = ), p=0.36 Clopidogrel Ticagrelor treatment duration, days 223 (28 353) 226 (26 364) No. at risk Ticagrelor Clopidogrel Months from randomization 9,235 7,289 6,862 6,570 5,144 3,775 3,414 9,186 7,320 6,936 6,657 5,209 3,843 3,470

48 Study medication pre- and post-cabg CABG Days study drug stopped before CABG, % 1 day 2 days 3 days 4 days 5 days 6 days 7 days Ticagrelor (n=632) Clopidogrel (n=629) Patients not restarted on study drug/unknown n=234 n=238 Time study drug restarted after CABG, % (n=398) (n=391) <7 days 7 14 days >14 days Held et al. JACC 2011; 57(6):

49 Study medication pre- and post-cabg CABG Days study drug stopped before CABG, % 1 day 2 days 3 days 4 days 5 days 6 days 7 days Ticagrelor (n=632) Clopidogrel (n=629) Patients not restarted on study drug/unknown n=234 n=238 Time study drug restarted after CABG, % (n=398) (n=391) <7 days 7 14 days >14 days Held et al. JACC 2011; 57(6):

50 K-M estimated rate (%) Time from CABG to any death CABG 10 9 HR: 0.49 (95% CI ), p<0.01 Clopidogrel Ticagrelor No. at risk Ticagrelor Clopidogrel Months Held et al. JACC 2011; 57(6):

51 Smith et al. JACC 2012 (July 31);60(5):388-96

52 Smith et al. JACC 2012 (July 31);60(5):388-96

53 Smith et al. JACC 2012 (July 31);60(5):388-96

54 Prasugrel Clopidogrel 51% 57%

55 Chest Tube 12hr by Days from Last Dose of Study Drug to CABG Mean blood loss: Prasugrel Clopidogrel 655 ± 580 ml vs. 503 ± 378 ml (p=0.05) 81

56 All Cause Death Smith et al. JACC 2012 (July 31);60(5):388-96

57 Varenhost et al. JACC Oct 2012:

58 Time to Death due to Bleeding and Infection (primary cause or contributing) Varenhost et al. JACC Oct 2012:

59 Conclusion Based on the existing date and current guidelines it is recommended to initiate DAPT ASAP especially before performing PCI. Symptoms onset and identification Call EMS Pre-hospital ER Cath Lab phase Increasing Loss of Myocytes

60 The question whether further benefit can be achieved by earlier initiation of DAPT at 1 st medical contact is currently under examination by a number of prospective trials Symptoms onset and identification Call EMS Pre-hospital ER Cath Lab phase Increasing Loss of Myocytes

61 ATLANTIC: Study Design FIRST MEDICAL CONTACT CATH LAB ENTRANCE Eligible ICF Myocardial Infarction Diagnosis ECG Physical examination Physical examination ECG Angiography / PCI AMBULANCE HOSPITAL Visit 1 : Randomisation Visit 2 : Cath Lab Visit 3 : Day 1 ICU Visit 4 : Discharge ICU Visit 5 : Day 30 End of treatment Visit 6 : Day 37 Follow-up DOUBLE BLIND PERIOD ACTIVE TREATMENT PERIOD Ticagrelor 180mg Placebo Ticagrelor 90 mg x 2/day (30 days) Placebo Ticagrelor 180mg Full ICF

62 Platelet activation plays a major role in thrombus formation and pathogenesis of ACS Coronary plaque Erosion/rupture Thrombotic occlusion DAPT became a cornerstone of the treatment for ACS Davies MJ. Am J Cardiol Aug 16;88(4A):2F-9F

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64 Should DAPT be given ASAP 1 st medical contact)? How important is to achieve effective/optimal platelet inhibition before PCI?

65 TIMI-3 Flow Before PPCI for STEMI Is an Independent Determinant of Survival PAMI Trials Gregg W. Stone Circulation 2001;104:636

66 Can We do Better?