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Patient Oriented Therapy for STE-MI Seçkin Pehlivanoğlu, MD Başkent University, İstanbul Hospital.

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Presentation on theme: "Patient Oriented Therapy for STE-MI Seçkin Pehlivanoğlu, MD Başkent University, İstanbul Hospital."— Presentation transcript:

1 Patient Oriented Therapy for STE-MI Seçkin Pehlivanoğlu, MD Başkent University, İstanbul Hospital

2 Patient Oriented Therapy for STE-MI Q: What are the spesific conditions that will make a difference with individual patients treatmet ? 1)Diagnostic level 2)Prognostic level (risk stratification) 3)Therapeutic level

3

4 M. Cohen et al. JACC : Patient Oriented Therapy for STE-MI

5 Choice of Reperfusion Therapy Primary PCI vs FLT Acceptable time-window for PPCI ?

6 STE-AMI : Reperfusion Therapy (2007) STEMI patients presenting to a hospital with PCI capability should be treated with Primary PCI within 90 minutes of first medical contact (FMC) I I I IIa IIb III I I I IIa IIb III I I I IIa IIb III IIa IIb III I I I IIa IIb III I I I IIa IIb III I I I IIa IIb III IIa IIb III STEMI patients presenting to a hospital without PCI capability and who cannot be transfered to a PCI center and undergo PCI within 90 minutes of FMC should be tretated with Fibrinolytic therapy (FLT) within 30 minutes of hospital presentation as a system goal unless FLT is contraindicated

7 STE-AMI : Reperfusion Therapy (2008)

8 Primary PCI vs Fibrinolysis Time dependant benefit Meta-analysis of 23 trials of 1ry PCI vs fibrinolysis relating 4-6 week death difference to PCI-related time delay. Am J Cardiol 2003; 92:824 Mortality benefit of Primary PCI may be lost if door-to-balloon time is delayed by >60 min compared with door-to-needle time

9 NRMI (National Registry of Myocardial Infarction) patient Primary PCI related delay (min) (Door-Balloon – Door- Needle) PCI better Fibrinolysis Better Odds of Death with Fibrinolysis Primary PCI vs Fibrinolysis Time dependant benefit ConclusionsAs DB-DN times increase, the mortality advantage of PPCI over fibrinolysis declines, and this advantage varies considerably depending on patient characteristics. Circulation. 2006;114:

10 Circulation. 2006;113: In hospital mortality (%) Time to Reperfusion - Mortality

11 Patients (%) What has changed with Primary PCI patients? Percent of PPCI patiens of DBT<90 min Analysis according to the transfer status What has changed with Primary PCI patients? Percent of PPCI patiens of DBT<90 min Analysis according to the transfer status %34.3 %52.6 Discharged year %3.7 %9.0 Not Transfered Transfered NRMI 2 NRMI 3 NRMI 4 NRMI 5

12 Untimely reperfusion (after hospital presentation): - Fibrinolytic therapy > 30 min (54%) - Primary PCI > 90 min (68%) JAMA 2010; 303(21):

13 Patient Oriented Therapy for STE-MI Regardless of the mode of the therapy, primary goal should be to minimize total ischemic time; time from onset of symptoms to initiation of reperfusion therapy TIMELY REPERFUSION Choice of Reperfusion Therapy Primary PCI vs FLT

14 Patient Oriented Therapy for STE-MI Fibrinolytic Therapy – Secondary PCI Triage and Transfer for PCITriage and Transfer for PCI

15 STE-AMI : Triage and Transfer for PCI

16 STE-AMI : Pharmacoinvasive strategy The high risk patients who receive FLT as a primary reperfusion therapy at a non-PCI hospital can be transfered to a PCI-hospital inorder to perform PCI as a part of pharmacoinvasive strategy

17 17 CARESS-IN-AMI primary outcome :composite of all cause mortality, reinfarction, & refractory MI within 30 days 10.7% 4.4% HR=0.40 ( ) Di Mario et al. Lancet 2008;371. High risk STEMI (<12 hours) With one or more high-risk features: –extensive ST-segment elevation –new-onset left bundle branch block –previous MI –Killip class >2, or –left ventricular ejection fraction <35% for inferior MIs; Anterior MI alone with 2 mm or more ST-elevation in 2 or more leads Non-PCI hospital: Non-PCI hospital: half-dose lytic (reteplase) + abciximab + UFH

18 17.2% 11.0% Cumulative Incidence Days p=0.004 RR= 0.64, 95 CI% ( ) ACC/2008 N Engl J Med 2009;360: primary end point: composite of death, reinfarction, recurrent ischemia, new or worsening CHF, or shock within 30 days High risk STEMI (<12 hours) ANTERIOR MI 2 mm ST-segment elevation in 2 anterior leads INFERIOR MI 1 mm ST-segment elevation in 2 inferior leads and at least one of the following: SBP < 100 HR > 100 Killip Class II-III 2mm ST-segment depression in anterior leads 1 mm ST-segment elevation in V 4 R Non-PCI hospital: TNK + ASA + Heparin / Enoxaparin + Clopidogrel

19 Benefit 0-3 h Harm >3 h Benefit 12 h Benefit 24 h Benefit Hours Risc of Death Fibrinolytic therapy Rescue PCI Faciliated PCI Systematic PCI Late PCI for occluded IRA Harvey White; Circulation 2008;118: Faciliated PCI Pharmacoinvasive strategy No Benefit STE-AMI : Triage and Transfer for PCI

20 Patient Oriented Therapy for STE-MI Fibrinolytic Therapy – Secondary PCI Clopidogrel pretreatment

21 Clopidogrel in STEMI Fibrinolytic, ASA, Heparin Clopidogrel 300 mg + 75 mg qd Coronary Angiogram (2-8 days) Primary endpoint: Occluded artery (TIMI Flow Grade 0/1) or D/MI by time of angio randomize Placebo Double-blind, randomized, placebo-controlled trial in 3491 patients, age yrs with STEMI < 12 hours Study Drug 30-day clinical follow-up Open-label clopidogrel per MD in both groups Sabatine MS et al. NEJM 2005; 352

22 PlaceboClopidogrel 36% P< % P< Sabatine MS et al. NEJM 2005; 352: 1179 days CV Death, MI, or Urg Revasc (%) Placebo Clopidogrel Odds Ratio 0.80 (95% CI ) P= %20% Clopidogrel in STEMI Coronary Angiogram (2-8 days)

23 CV Death, MI, or Stroke following PCI Days post PCI Percentage with outcome (%) No Pretreatment – 6.2% Clopidogrel – 3.6% Pretreatment 46%46% Odds Ratio 0.54 (95% CI ) P=0.008 Odds Ratio 0.54 (95% CI ) P=0.008 Sabatine MS et al. JAMA 2005;294: PCI-CLARITY Clopidogrel in STEMI

24 9% relative risk reduction (P=.002) Placebo (10.1%) Clopidogrel (9.3%) Days Death, MI, Stroke (%) Mortality (%) Days Placebo (8.1%) Clopidogrel (7.5%) 7% relative risk reduction (P=.03) COMMIT Collaborative Group. Lancet. 2005;366: ,851 Patients STEMI w/in 24 hrs; ASA; lytic therapy (~1/2) Clopidogrel in STEMI

25 Fibrinolytic Therapy – Secondary PCI Clopidogrel pretreatment

26 Patient Oriented Therapy for STE-MI Adjunctive Antiplatelet Therapy Clopidorel vs Prasugrel /Ticagrelor

27 TRITON allowed recruitment of STEMI patients undergoing primary PCI when they presented < 12 hours of symptom onset or secondary PCI when they presented late P=0.03 P=0.01 P=0.002 Wiviott et al. New Engl J Med 2007;357: HR 0.81 ( ) Days CV Death, MI, Stroke (%) NNT= 46 Prasugrel Clopidogrel P<0.001 TRITON-TIMI 38 : Main study cohort

28 Clopidogrel Under Fire: Is Prasugrel in Primary PCI or Recent MI Superior? Insights From TRITON-TIMI-38 Gilles Montalescot, Stephen D. Wiviott, Eugene Braunwald, Sabina A. Murphy, C. Michael Gibson, Carolyn H. McCabe and Elliott M. Antman, for the TRITON–TIMI 38 Investigators Montalescot et al. ESC 2008 All ACS/PCI patients N=13608 UA/NSTEMI patients N=10074 STEMI patients N=3534 Primary PCI N=2438 (69%) Secondary PCI N=1094 (31%)* ClopidogrelN=1235PrasugrelN=1203 ClopidogrelN=530PrasugrelN=564

29 Montalescot et al. ESC 2008 Time (Days) Proportion of patients (%) HR=0.79 (0.65–0.97) NNT=42 p=0.02 RRR=21% p=0.002 RRR=32% Clopidogrel Prasugrel Age-adjusted HR=0.81 ( ) TRITON-TIMI 38 : STEMI Primary EP (CV death, MI and stroke at 15 months) 30 days

30 Montalescot et al. ESC 2008 * ARC def/probable All DeathMIUTVRStent Thrombosis* CV Death/ MI CV Death/ MI/UTVR CV Death/ MI/Stroke Proportion of population (%) p= 0.04 p= 0.01 p= 0.13 p= p= p= 0.02 p= Clopidogrel Prasugrel Efficacy endpoints at 30 days TRITON-TIMI 38 : STEMI

31 Montalescot et al ESC 2008 Prasugrel was superior to standard dose clopidogrel to prevent ischaemic events Prasugrel did not have more bleeding events compared to those who were treated with clopidogrel, and this was equally true for: – Primary PCI – Secondary PCI – Major bleeding – Minor bleeding Conclusions In STEMI patients undergoing PCI TRITON-TIMI 38 : STEMI These data make prasugrel an especially attractive alternative to clopidogrel in PCI for STEMI

32 STE-AMI : Adjunctive Antiplatelet Therapy (2009) Choice of Thienopyridine for PCI in STEMI: Prasugrel is not not endorsed explicitly over Clopidogrel - Benefit is predominantly by reduction in non-fatal MI (Death & nonfatal stroke similar + increased hemorraghic risk) - Loading dose of Cloidogrel (300 mg – TRINITON TIMI 38) was lower tha currently recommended doses

33 18,758 patients enrolled in PLATO 134 patients not randomized 18,624 patients randomized NSTEMI/UA/other: 10,194 patients STEMI 8,430 pts Randomized to ticagrelor: efficacy population N= 4,201 Randomized to clopidogrel: efficacy population N= 4,229 No intake of study medication: 36 patients No intake of study medication: 48 patients Safety population N=4,165 Safety population N=4,181 PLATO STEMI

34 Primary endpoint: CV death, MI or stroke Months HR: 0.85 (95% CI = 0.74–0.97), p=0.02 No. at risk Clopidogrel Ticagrelor 4,229 4,201 3,892 3,887 3,823 3,834 3,7303,022 3,011 2,333 2,297 1,868 1,8913, Clopidogrel Ticagrelor K-M estimated rate (% per year) PLATO STEMI

35 K-M estimated rate (% per year) Months Clopidogrel Ticagrelor Primary safety event: major bleeding HR 0.96 (95% CI = 0.83–1.12), p=0.63 PLATO STEMI

36 Hierarchical testing of major efficacy endpoints Endpoint* Ticagrelor (n=4,201) Clopidog rel (n=4,229) HR for ticagrelor (95% CI) p- value Primary endpoint, % CV death + MI + stroke (0.74–0.97)0.02 Secondary endpoints, % Total death + MI + stroke CV death + MI + stroke + ischaemia + TIA + arterial thrombotic events MI CV death Stroke (0.73–0.96) 0.86 (0.76–0.96) 0.77 (0.63–0.93) 0.84 (0.69–1.03) 1.45 (0.98–2.17) All-cause mortality (0.68–0.99)0.04 PLATO STEMI

37 Conclusions Reversible, more intense P2Y 12 receptor inhibition for one year with ticagrelor in comparison with clopidogrel in patients with STEMI intended for reperfusion with primary PCI provides – Reduction in composite of CV death, MI or stroke – Reduction in MI and stent thrombosis – Reduction in total mortality – No increase in the risk of major bleeding The mortality reduction is afforded on top of modern care Ticagrelor may become a new standard of care for the management of patients with STEMI intended for primary PCI PLATO STEMI

38 Patient Oriented Therapy for STE-MI Adjunctive Antiplatelet Therapy Clopidogrel: Double dose vs Standart dose

39 25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2% ) Planned Early (<24 h) Invasive Management with intended PCI Planned Early (<24 h) Invasive Management with intended PCI Ischemic ECG Δ (80.8%) or cardiac biomarker (42%) Ischemic ECG Δ (80.8%) or cardiac biomarker (42%) 25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2% ) Planned Early (<24 h) Invasive Management with intended PCI Planned Early (<24 h) Invasive Management with intended PCI Ischemic ECG Δ (80.8%) or cardiac biomarker (42%) Ischemic ECG Δ (80.8%) or cardiac biomarker (42%) PCI 17,232 (70%) Angio 24,769 (99%) (99%) No PCI 7,855 (30%) No Sig. CAD 3,616 CABG 1,809CAD 2,430 Randomized to receive (2 X 2 factorial): CLOPIDOGREL: Double-dose (600 mg then150 mg/d x 7d then 75 mg/d) vs Standard dose (300 mg) then 75 mg/d) ASA: High Dose ( mg/d) vs Low dose ( mg/d) Efficacy Outcomes:CV Death, MI or stroke at day 30 Stent Thrombosis at day 30 Safety Outcomes:Bleeding (CURRENT defined Major/Severe and TIMI Major) Key Subgroup: PCI v No PCI Clop in 1st 7d (median) 7d 7 d 2 d 7d Complete Followup 99.8% Compliance: Clopidogrel: Double vs Standard Dose

40 StandardDoubleHR95% CIPIntn P CV Death/MI/Stroke PCI (2N=17,232) No PCI (2N=7855) Overall (2N=25,087) MI PCI (2N=17,232) No PCI (2N=7855) Overall (2N=25,087) CV Death PCI (2N=17,232) No PCI (2N=7855) Overall (2N=25,087) Stroke PCI (2N=17,232) No PCI (2N=7855) Overall (2N=25,087) Clopidogrel: Double vs Standard Dose Primary Outcome: PCI vs No-PCI

41 Days Cumulative Hazard Clopidogrel Standard Clopidogrel Double HR % CI P= % RRR CV Death, MI or Stroke Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients

42 CURRENT PCI N=17,232 TRITON N=13,608 CV Death, MI or Stroke 15% 21% (w high dose ASA) 19% Definite Stent Thrombosis 42% 51% (w high dose ASA) 58% TIMI Major BleedNo increase 32% CABG-related BleedingNo increase 4-fold Fatal bleedingNo increase 4-fold Comparison of CURRENT and TRITON

43 STE-AMI : Adjunctive Antiplatelet Therapy (2010)

44 STE-AMI : Adjunctive Antiplatelet Therapy (2011) Clopidogrel: Class I-B (PCI) 600 mg loading dose now recommended No spesific recommendation for STE-MI GP IIb/IIIa inhibitor : Class II-A May be most appropriate with large anterior MI and/or large thrombus burden IC abciximab (Class IIb-B) Precatheterization lab. GPI administration (Class III-no benefit) Antithrombin agents (UFH-Bivaluridine-Enoxaparine): No spesific recommendation for STE-MI

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