ST ELEVATION MYOCARDIAL INFARCTION

Transcription

1 ST ELEVATION MYOCARDIAL INFARCTION Doron Zahger, MD Dept. of Cardiology, Soroka University Medical Center Faculty of Health Sciences, Ben Gurion University of the Negev

2 MAIN TOPICS Adjuncts to thrombolysis Pre hospital thrombolysis PCI for STEMI The approach to reperfusion Guidelines based pharmacotherapy

3 ADJUNCTS TO LYSIS ANTI THROMBOTIC THERAPY

4 Protocol Design STEMI < 6 h Lytic eligible ASA Lytic choice by MD (TNK, tpa, rpa, SK) Double-blind, double-dummy ENOX < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC) UFH 60 U / kg bolus (4000 U) Inf 12 U / kg / h (1000 U / h) Duration: at least 48 h Cont d at MD discretion CrCl < 30: 1.0 mg / kg q 24 h Day 30 1 Efficacy Endpoint: Death or Nonfatal MI 1 Safety Endpoint: TIMI Major Hemorrhage

5 Primary End Point (ITT) Death or Nonfatal MI Primary End Point (%) 15 UFH % 17% RRR 9 9.9% ENOX Relative Risk 0.83 (0.77 to 0.90) P< Lost to follow up = Days

6 Net Clinical Benefit at 30 Days Prespecified Definitions Death or Nonfatal MI or Nonfatal Disabl. Stroke Death or Nonfatal MI or Nonfatal Major Bleed Death or Nonfatal MI or Nonfatal ICH UFH (%) ENOX (%) RRR (%) P < P < P < ENOX Better 1 RR 1.25 UFH Better

7 Clinical Implication A strategy of ENOX is clearly preferable to the current standard of UFH as the antithrombin to support fibrinolysis, the most common form of reperfusion for STEMI used worldwide.

8 Is that clearly so? EXTRACT did not convincingly show that Enoxaparin is superior to UFH while the 2 agents are actually administered. Only 23% of patients in EXTRACT had PCI. It is unlikely that with early PCI, as currently recommended, a significant difference exists between the 2 agents.

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10 OASIS-6: Study design Patients with STEMI randomized <12 h of symptom onset N = 12,092 Stratum I: UFH not indicated (receiving thrombolytics) (n = 5658) Fondaparinux 2.5 mg qd* (n = 2823) Placebo* (n = 2835) Stratum II: UFH indicated (receiving tpa or scheduled PCI) (n = 6434) Fondaparinux 2.5 mg qd + placebo* (n = 3213) UFH 60 IU/kg IV bolus/ 12 IU/kg h infusion + placebo* (n = 3221) Primary outcome: Composite of death or reinfarction at 30 days Main safety outcome: Severe bleeding *Up to 8 days (or earlier discharge) OASIS-6 Trial Group. JAMA. 2006;295:

11 OASIS-6: Treatment effect on primary efficacy outcome at 30 days Composite of death, MI Cumulative event rate HR 0.86 ( ) P = UFH or placebo Days Fondaparinux OASIS-6 Trial Group. JAMA. 2006;295:

12 OASIS-6: Severe bleeding at 30 days Modified TIMI criterion Cumulative event rate HR 0.79 ( ) P = UFH or placebo Days Fondaparinux OASIS-6 Trial Group. JAMA. 2006;295:

13 OASIS-6: Summary Fondaparinux demonstrated a moderate reduction in mortality and reinfarction vs UFH/placebo Unlike other antithrombotic agents (eg, LMW heparin, direct thrombin inhibitors, intravenous antiplatelet agents), fondaparinux reduced deaths and reinfarction without increased bleeding or hemorrhagic stroke There appears to be little advantage in using fondaparinux as the initial treatment in patients undergoing primary PCI OASIS-6 Trial Group. JAMA. 2006;295:

14 Anticoagulants I IIa IIb III Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a minimum of 48 hours (Level of Evidence: C) and preferably for the duration of the index hospitalization, up to 8 days I IIa IIb III (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment). ((Level of Evidence: A Anticoagulant regimens with established efficacy :include UFH ((LOE: C Enoxaparin ((LOE:A Fondaparinux ((LOE:B ACC/AHA 2007 STEMI Guidelin 14

15 ADJUNCTS TO LYSIS CLOPIDOGREL

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

17 Primary Endpoint: Occluded Artery or Death/MI (%) Occluded Artery (or D/MI thru Angio/HD) 25 36% 21.7 Odds Ratio 0.64 Odds Reduction (95% CI ) 15.0 P= n=1752 n=1739 Clopidogrel Placebo Clopidogrel better 1.6 Placebo better

18 Placebo 10 20% Clopidogrel 5 Odds Ratio 0.80 (95% CI ) P= Percentage with endpoint (%) 15 CV Death, MI, RI Urg Revasc days

19 Bleeding Outcome Clopidogrel Placebo P value (%) (%) Through angiography TIMI minor (Hgb 3-5 g/dl) NS NS Intracranial hemorrhage NS NS NS NS NS TIMI major (Hgb >5 g/dl or ICH) Through 30 days TIMI major In those undergoing CABG CABG w/in 5 d of study med TIMI minor

20 COMMIT/CCS-2 (ClOpidogrel & Metoprolol in Myocardial Infarction Trial) Designed, conducted, analysed and interpreted independently by COMMIT/CCS-2 collaboration Sources of funding (US$ 3M): SanofiAventis/BMS AstraZeneca British Heart Foundation UK Medical Research Council

21 Study Design1 *Clopidogrel 75 mg once daily (n=~23,000) Patients with acute STEMI 24 hours n=~46,000 R Double-blind treatment until hospital discharge or for a maximum of 4 weeks (n=~23,000) *Placebo (X 2 factorial with metoprolol 2) All patients received a background of ASA 162 mg/day* during the study CCS-2 Collaborative Group. J Cardiovasc Risk 2000; 7:

22 COMMIT: Effect of CLOPIDOGREL on Death in hospital Placebo + ASA: 1846 deaths (8.1%) Clopidogrel +ASA: 1728 deaths (7.5%) Dead (%) 7% (SE3) relative risk reduction (2P=0.03) Days since randomisation (up to 28 days)

23 COMMIT: Major bleed in hospital Type Clopidogrel Placebo (n=22,958) (n=22,891) Cerebral Fatal Non-fatal Non-cerebral Fatal Non-fatal Any major bleed (0.58%) (0.54%)

24 Thienopyridines I IIa IIb III Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or.do not receive reperfusion therapy I IIa IIb III Treatment with clopidogrel should continue.for at least 14 days ACC/AHA 2007 STEMI Guidelin 24

25 What is the optimal drug combination to support thrombolysis? Enoxaparin for 8d is better than 2d of UFH If coronary angiography is planned within 3-24 h post lysis, probably no advantage for enoxaparin Fondaprinux better than placebo but not proved more effective or safer than UFH. Fondaparinux vs. Enoxaparin -? Clopidogrel reduces mortality

26 What is the optimal drug combination to support thrombolysis? The safety of clopidogrel + fondaprinux post lysis is uncertain (rare early use of clopidogrel in OASIS 6). Clopidogrel + enoxaparin probably reasonable (30% in CLARITY) Clopidogrel + enoxaparin is probably the best evidence-based combination when early PCI is not routinely performed.

27 Pre hospital lysis Meta analysis of large trials suggests 15-20% reduction in mortality with pre hospital (vs. hospital based) lysis Benefit is maximized during first 2 hours (44% reduction). FFT estimate: benefit declines by 1.6 deaths prevented for 1000 patients treated, for every hour of delay.

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30 CAPTIM: TIME TO TREATMENT AND MORTALITY Steg, P. G. et al. Circulation 2003;108: Copyright 2003 American Heart Association

31 CAPTIM 1 Year Results Sx > 2 hours Death Death Sx < 2 hours Death Death P=0.057 P=0.057 P=0.47 P= % 10% 5.7% 5.7% 5.9% 5.9% 5% 5% 3.7% 3.7% 2.2% 2.2% 0% 0% 0% 0% Pre Pre Hospital Hospital Lysis Lysis Primary Primary PCI PCI Pre Pre Hospital Hospital Lysis Lysis Primary Primary PCI PCI GW GW Symposium, Symposium, AHA AHA

32 One-year survival according to use and type of reperfusion therapy Lysis: 2/3 pre hospital, 70% treated <3h Danchin, N. et al. Circulation 2008;118: Copyright 2008 American Heart Association

33 N=26,205 PCI>pre hospital lysis>hospital 30d, 1 year p<0.05

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35 PCI FOR STEMI Primary PCI Vs. thrombolysis Transfer to primary PCI Facilitated primary PCI Rescue PCI for failed lysis Routine post lysis PCI Routine delayed PCI post non reperfused MI

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37 PCI VS. LYSIS: META ANALYSIS OF 23 TRIALS

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42 Adjusted analysis illustrating significant heterogeneity in the PCI-related delay (DB-DN time) for which the mortality rates with primary PCI and fibrinolysis were comparable after the study population was stratified by prehospital delay, location of infarct, and age Pinto, D. S. et al. Circulation 2006;114: Copyright 2006 American Heart Association

43 Mortality rates for low-risk patients treated with fibrinolysis (Fx) (black dashed line) or primary angioplasty (PA) (red dashed line) and high-risk patients treated with fibrinolysis ((black solid line) or primary angioplasty (red solid line Thune, J. J. et al. Circulation 2005;112: Copyright 2005 American Heart Association

44 NRMI-2: Primary PCI Distribution of Door-to-Balloon times 30 N=27,080 % of Patients Door-to-Balloon Time (minutes) >180 Cannon CP, et al JAMA: June 2000.

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46 PRAGUE 2 5 YEAR FOLLOW UP Eur Heart J 2007;28:679

47 Relationship between delay in transferring patients for primary PCI and one-year mortality Interhospital delay (mins) < >90 p (n=94) (n=188) (n=194) (n=140) 1-y mortality (%) De Luca G et al. Am J Cardiol 2005; 95:

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49 Conclusions When transport time does not exceed minutes, and a competent team is on standby at the receiving hospital, transfer to PCI is superior to local lysis. Pre-hospital lysis might be as good as primary PCI, provided rescue procedures are available.

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51 FACILITATION BY THROMBOLYSIS

52 ASSENT- 4 PCI Trial 1667 patients with STEMI, within 6 hrs; intent to perform primary PCI Randomized Mean follow-up: 6 mos (30 days reported to date) 63% of patients received clopidogrel/ticlopidine during PCI Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group Full-dose TNK + Primary PCI 70 IU/kg, no maximum dose 60 IU/kg, maximum 4000 IU n=838 n=829 GP IIb/IIIa inhibitors allowed at physician discretion GP IIb/IIIa inhibitors allowed only for bail out use Primary PCI Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days. Presented at ESC 2005

53 ASSENT- 4 PCI Trial: TIMI Flow Grade TIMI grade 3 flow prior to PCI and TIMI grade 2/3 flow post-pci (%) p= % 100% 80% 60% 97.6% p< % TIMI grade 2/3 post-pci was slightly higher in the PCI alone group (95.3% vs 97.6%) 40% 20% 15.0% 0% TFG 3 prior to PCI TNK + PCI TIMI grade 3 flow prior to PCI was present more frequently in the TNK + PCI arm (43.6% vs 15.0%) TFG 2/3 post-pci PCI alone Presented at ESC 2005

54 PRIMARY ENDPOINT: 90 d P=0.0045

55 ASSENT- 4 PCI Trial: Mortality at 30 days Analysis of mortality at 30 days (%) p = % 6% 6.0% 3.8% 4% The primary endpoint of mortality was higher in the TNK + PCI treatment group compared with the PCI alone group (6.0% vs 3.8%, p=0.04) at 30 days 2% 0% n=50 TNK + PCI n=32 PCI alone Presented at ESC 2005

56 FACILITATION BY IIb/IIIa ANTAGONISTS

57 ADMIRAL Design AMI < 12 hours randomization Abciximab + Heparin, ASA, Ticlopidine Placebo + Heparin, ASA, Ticlopidine First Coronary Angiography PTCA + Stent First Coronary Angiography PTCA + Stent Coronary Angiography at 24 h and 6 Months Coronary Angiography at 24 h and 6 Months Clinical evaluation (24 h, 30 Days and 6 Months ESC 1999, Oral Presentation

58 ADMIRAL Primary Endpoint (30 days) D e a th, R e c u rre n t M I, U rg e n t T V R 20 p = % % of Patients Placebo n = 150 Abciximab n = 150 ESC 1999, Oral Presentation

59 P P R Death/MI R Death

60 The FINESSE Trial (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events) Final 90 Day Results in Perspective Stephen Ellis, MD for the FINESSE Investigators AHA 2007 Conflicts: research grant Centocor/Lilly/Cordis

61 FINESSE: Study Design Acute ST Elevation MI (or New LBBB) within 6h pain onset Presenting at Hub or Spoke with estimated time to Cath between 1 and 4 hours Randomize 1:1:1 N=3000 Double Blind Double Dummy Placebo Placebo Placebo Abciximab 75 yr Only 5U if* *(Reteplase (5U+5U Abciximab Transfer To Cath Lab (ASA, unfractionated heparin 40U/kg (max 3000U or enoxaparin (0.5 mg/kg IV mg/kg SC) substudy only Abciximab Placebo (Primary PCI with Abciximab Infusion (12 h Follow up through 90 days and 1 year Placebo

62 TIMI Flow in IRA Pre-PCI % Subjects with TIMI 2/3 (Patency) Pre-PCI 100% 90% p< % Percentage 70% p< % 61% 50% 25% TIMI 2 36% TIMI 3 40% 25% 30% 20% 10% 0% 26% 12% 11% 13% 15% Primary PCI (in lab Abciximab) (n=790) 74min Abciximab Facilitated Reteplase/Abciximab PCI (n=809) Facilitated PCI (n=815) Ave Time from First Abciximab Bolus 76minto Angiogram In Facilitated Groups: Modified ITT Population with Index PCI: ITT, PCI and any dose of study drug (active or placebo); Investigator assessment

63 ST Segment Resolution (>70%) at Min: Core Lab % Evaluable Subjects with ST Segment Resolution Percentage 100% 80% p=0.003 p= % 40% p= % 33% p=ns p= % 44% 57% 64% 36% 23% 24% 20% 0% All (n=745) Prior to Balloon Inflation (n=525) After Balloon Inflation (n=154) Primary PCI with in lab Abciximab (n=242) Abciximab Facililated PCI (n=257) Reteplase/Abciximab Facilitated PCI (n=246) Half of subjects randomly selected for Core Lab over-read*

64 Primary Endpoint 10.7% 10.5% 9.8%

65 TIMI Major or Minor Bleeding (nonintracranial) through Discharge/Day7 TIMI Bleeding through Discharge/Day 7 30% Percentage 25% p<0.001 p=0.025 p=0.025 p=0.141 p=0.127 p=0.008 p=0.006 p= % p< % 15% 10% 5% 10.1% 9.7% 2.6% 4.1% 4.8% 4.3% 6.0% 6.9% 0% TIMI Major TIMI Minor TIMI Major or Minor Primary PCI with In Lab Abciximab (n=795) Abciximab Facililated PCI (n=805) Abciximab/Reteplase Facilitated PCI (n=814)

66 ON-TIME -2 Acute myocardial infarction diagnosed in ambulance or referral center ASA mg Clopidogrel + UFH Placebo N=984 6/ /2007 * Tirofiban Transportation Angiogram Tirofiban provisional PCI center PCI Angiogram Tirofiban cont d Bolus: 25 µg/kg & 0.15 µg/kg/min infusion*

67 On goingt irofibani nm yocardial InfarctionEvaluation Cumulative ST- Deviation over Time [mm] ± ±9.1 Placebo Tirofiban 12.1± ± ± ± ±4.3 p= ±6.3 Diagnosis pre Angio min min

68 On goingt irofibani nm yocardial InfarctionEvaluation Residual ST-Deviation and Mortality 30 day Mortality (%) 5 4 P< , ,6 ST dev <3mm ST dev >3mm

69 On goingt irofibani nm yocardial InfarctionEvaluation Summary Pre-Hospital initiation of tirofiban (HDB) improves ST resolution before and after primary PCI Combined secondary clinical endpoint reduced No increase in bleeding risk

70 Meta-analysis: Facilitated PCI vs Primary PCI Mortality Lytic alone N=2953 IIb/IIIa alone N=1148 Lytic +IIb/IIIa N=399 All (N=4500) Reinfarction ( ) ( ) 1.40 ( ) 1.03 ( ) ( ) ( ) 1.38 ( ) 0.1 Fac. PCI Better Major Bleeding 1.71 ( ) PPCI Better Keeley E, et al. Lancet.2006;367:579 Fac. PCI Better 1.51 ( ) 1 10 PPCI Better 0.1 Fac. PCI Better 1 10 PPCI Better ACC/AHA 2007 STEMI Guidelin 70

71 Conclusions Administration of lytics or GP IIb/IIIa antagonists prior to primary PCI markedly improves initial flow but has not been shown to improve outcome. Thrombolysis facilitation is probably harmful and should not be used. IIb/IIIa antagonists probably useful but facilitation may not be better than in lab administration. The use of these agents to facilitate PPCI may be justified when treatment delays are expected and bleeding risk is low. The use of abciximab with primary PCI is a class IIa recommendation in both ESC and ACC/AHA STEMI guidelines

72 Facilitated PCI I IIa IIb III I IIa IIb III A planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI is not recommended.and may be harmful Facilitated PCI using regimens other than full-dose fibrinolytic therapy might be considered as a reperfusion :strategy when all of the following are present,a. Patients are at high risk b. PCI is not immediately available within 90 minutes, and c. Bleeding risk is low (younger age, absence of poorly.(controlled hypertension, normal body weight ACC/AHA 2007 STEMI Guidelin 72

73 Harmonizing Outcomes with Revascularization and Stents in AMI pts with STEMI with symptom onset 12 hours *3400 Aspirin, thienopyridine UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) R 1:1 Bivalirudin monotherapy (provisional GP IIb/IIIa ±) Pharmacology Arm *Primary Endpoints Day 30 Intention to Treat Population All stent randomization results are still blinded *

74 (Heparin + GPIIb/IIIa inhibitor (n=1802 (Bivalirudin monotherapy (n=1800 *(%) Net adverse clinical events Primary Endpoint 30 Day Net Adverse Clinical Events 12.2% 9.3% = [HR [95%CI [0.92,0.62] 0.75 P=0.006 Time in Days Number at risk Bivalirudin Heparin + GPIIb/IIIa 1482 or major bleeding (MACE (non CABG*

75 30 Day Major Bleeding (non-cabg) Primary Endpoint (%) Major Bleeding (Heparin + GPIIb/IIIa inhibitor (n=1802 (Bivalirudin monotherapy (n= % 5.0% = [HR [95%CI [0.76,0.45] 0.59 P< Time in Days Number at risk Bivalirudin Heparin + GPIIb/IIIa

76 30 Day Major Adverse CV Events *(%) Major adverse CV events (Heparin + GPIIb/IIIa inhibitor (n=1802 (Bivalirudin monotherapy (n= % 5.5% = [HR [95%CI [1.32,0.75] 1.00 P=0.98 Time in Days Number at risk Bivalirudin Heparin + GPIIb/IIIa MACE death, reinfarction, ischemic TVR or stroke* 1590 = All cause

77 30 Day Mortality (%) Death (Heparin + GPIIb/IIIa inhibitor (n=1802 (Bivalirudin monotherapy (n= % 2.1% = [HR [95%CI [1.00,0.44] 0.66 P=0.048 Time in Days Number at risk Bivalirudin Heparin + GPIIb/IIIa

78 REACT: 6 month results 427 Acute MI patients with failed thrombolysis aspirin and thrombolytic therapy within 6 hours of chest pain onset, <50% ST resolution at 90 minutes, 42% anterior infarctions Repeat Thrombolysis Accelerated tpa or reteplase Rescue PCI Angiography with or without Revascularization n=142 n=144 Conservative Treatment IV Unfractionated Heparin for 24 hours n=141 Primary Endpoint: Composite of death, reinfarction, CVA, or severe heart failure at 6 months www. Clinical trial results.org Presented at AHA 2004

79 REACT: 6 month results Primary Composite Endpoint (Death, MI, CVA, or severe heart failure) p<0.001 p= % Repeat Thrombolysis www. Clinical trial results.org Rescue PCI Conservative Management

80 Rescue PCI I IIa IIb III A strategy of coronary angiography with intent to perform rescue PCI is reasonable for patients in whom fibrinolytic therapy has failed (ST-segment elevation < 50% resolved after 90 min following initiation of fibrinolytic therapy in the lead showing the worst initial elevation) and a moderate or large area of myocardium at risk [anterior MI, inferior MI with right ventricular involvement or precordial ST-segment depression]. ACC/AHA 2007 STEMI Guidelin 80

81 STUDIES OF ROUTINE EARLY PCI VS. DELAYED OR GUIDED PCI Death Collet et al, JACC 2006;48:1326 Death/MI

82 TRANSFER-MI Trial Design: TRANSFER-MI was a randomized study comparing pharmacoinvasive strategy (transfer to PCI center for routine early PCI within 6 hrs) with standard treatment (early transfer only for failed reperfusion) for high-risk STEMI patients receiving thrombolysis at non-pci centers (N=1,060). The primary endpoint was 30-day.composite of death, reinfarction, recurrent Ischemia, CHF, shock Day Composite (death, reinfarction, 30 (recurrent ischemia, CHF, shock OR = p = % of pts Results Early PCIwithin 6 hrs after thrombolysis was associated with a 6% absolute reduction in the primary study composite endpoint. Standard 16.6% vs Pharmacoinvasive 10.6% (OR = = [.368, 0.783]: p = ((Figure Conclusions 10 Challenges findings of older studies regarding timing of fibrinolysis and PCI Pharmacoinvasive strategy was safe and effective Findings provide important information for shaping future guidelines Standard Pharmacoinvasive Kastrani, K et al. Presented at ACC, 2008.@2008, American Heart Association. All rights reserved

83 CARESS-in-AMI Trial design: STEMI patients admitted to non-pci hospitals and initially treated with heparin, half-dose reteplase, and abciximab were randomized to immediate transfer for.(urgent PCI (n = 299) or standard therapy with rescue PCI if needed (n = 301 Results (p = 0.005) (p = 0.47) 86% of the immediate PCI group underwent PCI vs. 30% of the standard care group Death, MI, or refractory ischemia at 30 days (4.4% vs. 10.7%, p = 0.005) 10.7 % 4.4 MACE Refractory ischemia (0.3% vs. 4.0%, p = 0.003) Major bleeding Transfer for PCI Standard therapy (n = 299) (n = 301) Conclusions STEMI patients treated with half-dose lytics and abciximab did better with immediate transfer for PCI This approach reduced death, MI, or refractory ischemia at 30 days Benefit driven by reduction in refractory ischemia Di Mario C, et al. Lancet 2008;371:559-68

84 OAT Trial: Stud y De sign patients with angiography on day 3-28 post-mi revealing total occlusion 2166 of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and meeting a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both Exclusions: NYHA class III or IV heart failure, shock, serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe.ischemia on stress testing.randomized female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline 22%,Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers and lipid-lowering therapy, unless contraindicated PCI with stenting n=1082 Medical Therapy n=1084 Primary Endpoints: Death, MI, or NYHA class IV heart failure P r esented at A HA

85 OAT Trial: Prim ar y End po int P r im a r y E n d p o in t o f d e a t h, r e in f a r c t io n, N Y H A c la s s IV h e a r t ( f a ilu r e ( % p a t ie n t s 20% 15% H a z a r d R a t i o , p = % 15.6% 10% 5% 0% Weight PCI Th e prim ary e nd po int: d e ath, re infarc tio n, o r NYHA c lass IV h e art failure o c c urre d in % o f th e PCI gro up and % o f th e m e d ic al th e rapy gro up ([HR] 1.1 6,.(p=0.2 0 Medical Therapy P r esented at A HA

86 OAT Trial: Re sults P r im a r y Co m p o n e n t E n d p o in t s ( % ( p a t ie n t s PCI Medical Therapy 15 p< patients % p= p=0.0 8 p= p= Nonfatal Repeated Reinfarction Reinfarction of Cardiac Total Biomarkers Death NYHA Class IV Heart Failure To tal re infarc tio n tre nd e d h igh e r in th e PCI gro up (7.0 % vs. 5.3 %, HR1.3 6, p=0.1 3 ), as d id no nfatal re infarc tio n (6.9 %.(vs. 5.0 %, HR1.4 4, p=0.0 8 Re pe ate d e le vatio n o f c ard iac b io m arke rs w ith in 4 8 h o urs o f rand o m izatio n o c c urre d signific antly m o re fre q ue ntly in th e PCI gro up (1 0.0 % vs. 3.3 %,.(p< Th e re w as no d iffe re nc e in th e ind ivid ual e nd po ints o f d e ath (9.1 % fo r PCI vs. 9.4 % fo r m e d ic al th e rapy, p=0.8 3 ) o r NYHA c lass IVh e art failure (4.4 % vs. 4.5 %, p=0.9 2 ).b e tw e e n th e tre atm e nt gro ups

87 OAT Trial: Sum m ar y In stab le, h igh -risk patie nts w ith pe rsiste nt to tal o c c lusio n o f th e infarc t-re late d ar te r y po st-mi, c o m pare d to m axim um m e d ic al th e rapy, ro utine PCI d ays po st-mi w as no t asso c iate d w ith a d iffe re nc e in th e c o m po site o f d e ath, re infarc tio n, o r NYHA c lass IVh e ar t failure th ro ugh a m e an fo llo w -up o f 3 ye ars. De spite no re d uc tio n in th e c o m po site e nd po int, PCI w as asso c iate d w ith a tre nd to w ard h igh e r rate s o f re infarc tio n c o m pare d w ith m e d ic atio n th e rapy. Myo c ard ial infarc tio ns w e re no t o nly pro c e d ural-re late d infarc ts, b ut also ST e le vatio n MI o c c urring th ro ugh o ut fo llo w -up. P r esented at A HA

88 Coronary angiography post thrombolysis: Guidelines ACC/AHA: Class I/IIA for recurrent or provocable, ischemia, LV dysfunction, hemodynamic compromise Class IIb: Routine post thrombolysis ESC: Class I as routine post thrombolysis

89 Late PCI after Fibrinolysis or for Patients Not Undergoing Primary Reperfusion I IIa IIb III PCI of a hemodynamically significant stenosis in a patent infarct artery > 24 hours after STEMI may.be considered as part of a invasive strategy I IIa IIb III PCI of a totally occluded infarct artery > 24 hours after STEMI is not recommended in asymptomatic patients with 1- or 2-vessel disease if they are hemodynamically and electrically stable and do.not have evidence of severe ischemia ACC/AHA 2007 STEMI Guidelin 89

90 PCI FOR STEMI Primary PCI Vs. thrombolysis - yes Transfer to primary PCI - yes Facilitated primary PCI with lysis no, with Reopro - possibly Rescue PCI for failed lysis - yes Routine early post lysis PCI - yes Routine delayed PCI post non reperfused MI - no

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92 THE APPROACH TO REPERFUSION THERAPY: I Pre hospital phase Determine a community policy for STEMI transfer STEMI < 12h ASA, UFH Contact receiving hospital Decide on destination hospital

93 THE APPROACH TO REPERFUSION THERAPY: I Pre hospital phase Time to PCI center< time to non PCI center PCI center Cardiogenic shock, other very high risk Time to PCI center > time to non PCI center C/I to lysis Expected time to balloon - time to t-pa <60 min Not high risk, Expected time to balloon >> time to t-pa Non PCI center

94 THE APPROACH TO REPERFUSION THERAPY: I Pre hospital phase Going to PCI center Consider abciximab Going to non PCI center Delay<20 min Transfer Delay>20 min Consider pre hospital lysis, especially if pain <3h

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97 Primary PCI I IIa IIb III I IIa IIb III STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within.90 min of first medical contact as a systems goal STEMI patients presenting to a hospital without PCI capability, and who cannot be transferred to a PCI center and undergo PCI within 90 min of first medical contact, should be treated with fibrinolytic therapy within 30 min of hospital presentation as a systems goal, unless fibrinolytic therapy is.contraindicated ACC/AHA 2007 STEMI Guidelin 97

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99 GUIDELINES - BASED PHARMACOTHERAPY OF STEMI (1) ACC/AHA ESC Class I for all, starting on presentation, indefinitely ASA UFH With primary PCI I With t-pa & variants I With SK if ant. MI, large MI, AF I Other SK IIb No reperfusion IIa, at least 48h IIa

100 GUIDELINES - BASED PHARMACOTHERAPY OF STEMI (2) ACC/AHA LMWH With lytics I Anterior MI, large MI, AF I No reperfusion, low risk Bivalirudin IIa, at least 48h with PPCI Fonda With lytics Abciximab with PPCI Post stenting, lysis, Clopidogrel no reperfusion ESC IIa I IIa (STK) IIa I

101 GUIDELINES - BASED PHARMACOTHERAPY OF STEMI (3) ß blockers Early IV ACC/AHA ESC IIa, if hypertensive IIb I Hospital phase CCB Hospital phase with heart failure III Long term, low risk IIa I Verapamil/diltiaz em if ß blockers not tolerated IIa II With LV dysfunction III

102 GUIDELINES - BASED PHARMACOTHERAPY OF STEMI (4) ACC/AHA ACE - I STATINS ESC I 1ST 24h, low risk IIa Any LDL I LDL > 115 despite diet FIBRATE/ NIACIN WARFARIN LDL<100+ HDL <40 or TG>500 I ASA allergy, AF, LV clot With ASA if <75 I if HDL <45 + TG>200 I I IIa