- Primary PCI is the preferred reperfusion strategy for STEMI when it can be performed at an experienced center within 120 minutes of first medical contact. Fibrinolysis is an alternative if PCI cannot be performed within this time window.
- Clopidogrel in combination with aspirin results in significant improvements in outcomes for STEMI patients over aspirin alone based on the CLARITY-TIMI 28 and COMMIT trials.
- Enoxaparin is superior to unfractionated heparin as an anticoagulant to support reperfusion therapy for STEMI based on the ExTRACT-TIMI 25 trial.
1. STEMI – My Approach 2010 Dr S A Merchant Interventional Cardiologist DM MD DNB FSCAI Lilavati, CritiCare, BSES, Breach Candy Hospitals
2. Clinical manifestations of arterial thrombosis UA/NQMI:Partially-occlusive thrombus (primarily platelets) ST MI:occlusive thrombus (platelets, red blood cells, and fibrin) Intra-plaque thrombus (platelet dominated) Plaque core Intra-plaque thrombus (platelet dominated) Plaque core SUDDEN DEATH Adapted from Davies MJ. Circulation. 1990; 82 (supl II): 30-46. Dr S A Merchant
4. 68% 60 40 20 18% 14% 0 <50% 50%–70% >70% % Stenosis Small, vulnerable plaques are responsible for causing MI MI Patients (%) Falk et al: Circulation 1995;92:657–671 Dr S A Merchant
5. MANAGEMENT OF Acute Myocardial Infarction THE IMPACT OF MEDICAL THERAPY % Mortality Defibrillation, Hemodynamic monitoring Beta Blockade Thrombolysis/adjuct therapy PTCA, Stent Dr S A Merchant
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7. Consider prehospital fibrinolytic if capable and EMS–to–needle within 30 minOnset of symptoms of STEMI 9-1-1 EMS dispatch EMS triage plan PCI capable GOALS 5 min 8 min EMS transport Patient EMS Prehospital fibrinolysis EMS–to–needle ≤ 30 min EMS transport EMS–to–balloon ≤ 90 min Patient self-transport Hospital door–to–balloon ≤ 90 min Dispatch 1 min Total ischemic time: within 120 min “Golden Hour” = 1st 60 min Transport of Patients With STEMI and Initial Reperfusion Treatment J Am CollCardiol. 2004;44:671; Circulation. 2004;110:588.
8. Thrombolysis Versus Primary PCI - Time Dependancy Absolute 35 day mortality reduction v treatment delay N=50246 Primary PCI Boersma et al, Lancet 1996 348:771 Dr S A Merchant
12. primary PTCA vs stent 6-month outcomes stent PTCA OR (95% CI) 3.3% 1.7% 4.9% 8.3% 13.7% 3.8% 3.0% 6.8% 18% 25.9% death reMI death/ reMI TVR death/reMI/TVR 0.85 (0.57-1.27) 0.58 (0.35-0.96) 0.72 (0.52-0.98) 0.41 (0.32-0.52) 0.45 (0.37-0.55) 0 0.5 1.5 1 2 stentbetter PTCA better Dr S A Merchant
13. Real world situation: Door to balloon times in USA N=365 N Engl J Med 2006;355 Dr S A Merchant
14. Conclusion : Every minute delay in P’PCI affects 1 year mortality. Therefore, all efforts should be made to shorten Ischemia time not only for thrombolysis but also for P’PCI.
15.
16. Assessment of time is the key point in the choice of reperfusion strategyDr S A Merchant
17. USIC 2000, French Registry Data Hospital administered ‘lysis as good as PCI Pre hospital lysis EURO-PCR Paris 2003 Dr S A Merchant
18. French USIC 2000 survey: real world USIC. Circulation 2004;110:1909-1915 Dr S A Merchant
19. Fibrinolysis vs Transfer for PCI Pre HospPrimaryIn HospLysisPCILysisCAPTIM CAPTIM DANAMI 2 DANAMI 2 Death (%) 3.8 4.8 6.6 7.6 1yr 5.4 7.3 Reinfarction (%) 3.7 1.7 1.6 6.3 Disabling CVA (%) 1.0 0.0 1.1 2.0 Any of Above (%) 8.2 6.2 8.0 13.7*(* P < 0.003) VahanianESC, 2002 Dr S A Merchant
20. Pre Hospital thrombolysisCAPTIM 1 Year Results (TNK) Sx < 2 hours Death P=0.057 Pre Hospital Lysis Primary PCI GW Symposium, AHA 2002 Dr S A Merchant
21. Blush Score : 30 D, M in AMI receiving fibrinolysis regardless of TIMI Grade flow in Epicardial Artery, Myocardial perfusion by blush score predicts mortality Failed flows Gibson : Circulation 2000; 101-125 Improved flows
22. PTCA vsFibrinolysis:Short Term Clinical Outcomes (23 RCTs) PTCA P<0.0001 Fibrinolysis P<0.0001 Frequency (%) P=0.0002 P=0.0003 P<0.0001 P=0.032 P=0.0004 P<0.0001 Death Death, no SHOCKdata ReMI Rec. Isch Total Stroke Hem. Stroke Major Bleed DeathMICVA N = 7739 Keeley E. et al., Lancet 2003; 361:13-20.
23. Is timing an issue even for Primary PCI? Dr S A Merchant
26. NRMI-2 : 27080 consecutive patients 24% % of patients 21% 20% 20 17% 15 10% 10 8% 5 0 min <60 60-90 120-150 90-120 150-180 >180 C.P. CANNON. JAMA 2000;283:2941-7 door-to-balloon times in primary PCI Dr S A Merchant
27. Mortality by time to reperfusion with Primary PCINRMI-2 Registry (27,080) C.P. CANNON. JAMA 2000;283:2941-7 Dr S A Merchant
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29.
30. Why is Primary PCI less time dependent than Lysis? Lysis is less effective at restoring infarct artery patency as the clot ages Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion Cardiac rupture is more likely to occur as the time to lysis increases Dr S A Merchant
31.
32. PCI for AMI: door-to-balloon time < 2hrs (time window up to 12 hours accepted)* operator: 75 PCI (any type) / year; center: 36 Primary PCI / year Dr S A Merchant
33. After 12 hours??? BRAVE-2 Rationale: While thrombolysis has been shown to produce no benefit after 12 hours, no similar studies have looked at primary PCI in this group. Study: 365 patients randomized to in an invasive arm or a conservative arm. The invasive group underwent angiography and then PCI if necessary, while the conservative group was treated with conventional medical therapy. The primary end point was infarct size determined by SPECT at five to 10 days. Results: Infarct size (%LV) was significantly reduced in the invasive arm (8.0 vs 13%; p=0.002). No clinical differences. Kastrati ACC 2005 Dr S A Merchant
40. Exception: in case of cardiogenic shock, systematic intervention in multiple vessels may be required to optimize reperfusion of the heart. Dr S A Merchant
43. GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization 30% Placebo GP IIb/IIIa 26.1% 20% 14.6% 11.2% 9.7% 10% 6.8% 6.0% 5.8% 4.5% 4.5% 2.0% p = 0.06 p = 0.01 p = 0.03 p = 0.03 p = 0.02 0% CADILLAC EPIC RAPPORT Neumann ADMIRAL N: 64 483 200 300 2082
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45.
46. Types of Thrombolytics A. Clot Selective / Clot-Binding / fibrin Specific B. Non clot Selective/ Non–Clot-Binding / Non Fibrin Specific Dr S A Merchant
47. Clinical Relevance of Fibrin Affinity Action of Non–Clot-Binding Agents Action of Clot-Binding Agents (Urokinase, Streptokinase) (Alteplase, Tenecteplase) Clot-BindingPlasminogenActivators Clot Blood Vessel Non–Clot-BindingPlasminogenActivators Clot Blood Vessel Dr S A Merchant
66. total 528 6.7% 11.5% 0.55 (0.30-1.01) p=0.052 rescue PCI short termoutcome: death odds ratio (95% CI) n PCI cons. 0.13 (0.01-1.40) Belenkie RESCUE PRAGUE Vermeer 28 151 200 149 6.3% 5.1% 7% 8.7% 33.3% 9.6% 14.0% 6.7% 0.51 (0.12-2.06) 0.46 (0.16-1.30) 1.24 (0.31-4.49) 0 0.5 1.5 1 2.0 Dr S A Merchant
67. Incidence of Shock P=0.09 Pre Hospital Lysis Primary PCI CAPTIM – PrehospitaltPAvs 1°PCI1 Year Results Death at 1 Year P=0.27 Primary PCI Pre Hospital Lysis Bonnefoy Lancet 2002 Dr S A Merchant
68.
69. "Streptokinase is not very cath-lab friendly, so patients were more prone to getting bleeding complications when they went to the cath lab.
70. Those previous trials were also done before we knew the benefits of preloading patients with clopidogrel and using antithrombotic therapies like GP IIb/IIIa inhibitors during the angioplasty."Dr S A Merchant
76. ExTRACT TIMI 25Net Clinical Benefit at 30 Days UFH (%) Enox (%) RRR (%) Death / Nonfatal MI / Nonfatal Disabling Stroke 10.1 18 12.3 Death / Nonfatal MI / Nonfatal Major Bleed 11.0 14 12.8 Death / Nonfatal MI / Nonfatal ICH 10.1 17 12.2 Enox Better UFH Better RR Dr S A Merchant
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78.
79.
80.
81.
82. CLARITY–TIMI 281° Endpoint:Occluded Artery (or D/MI Thru Angio/HD) 36% odds reduction Odds ratio 0.64 (95% CI, 0.53 – 0.76) P < 0.001 Occluded artery or death/MI (%) n = 1,752 n = 1,739 | | | | | | 0.4 0.6 0.8 1.0 1.2 1.6 Clopidogrel Placebo LD 300 mg MD 75 mg Clopidogrel Placebo better better Sabatine MS, N Engl J Med. 2005;352:1179-1189. Dr S A Merchant
83. 10 9 8 7 6 5 4 3 2 1 0 0 7 14 21 28 COMMIT: Effect of Clopidogrel on Death Inhospital Placebo + ASA: 1,845 deaths (8.1%) Clopidogrel + ASA: 1,726 deaths (7.5%) Proportion dead before first discharge (%) 0.6% ARD7% RRR P = 0.03 N = 45,852 No age limit; 26% age ≥ 70 years Lytic Rx 50% No LD given Time since randomization (days) Chen ZM, et al. Lancet. 2005;366:1607-1621. Dr S A Merchant
90. Clopidogrel in combination with aspirin results in significant further improvements in outcomes of patients with STEMI (CLARITY-TIMI 28/COMMIT)Dr S A Merchant
91.
92. Enoxaparin is superior to current standard of UFH as the antithrombin to support fibrinolysis (ExTARCT TIMI 25)
93. Enoxaparin has a beneficial effect in patients undergoing elective PCI,with no increase in bleeding (PCI - ExTARCT TIMI 25)
94. Fondaparinux is beneficial in STEMI without increasing the risk of bleeding or stroke (OASIS 6), but some subsets do not benefit (eg primary PCI)
96. Long term treatment involves aggressive multifactorial lifestyle modification & both antithrombotic & anti ischemic therapiesDr S A Merchant
97. PCI p lytic Pharmacoinvasive approach Partial flow Complete obstruction Partial success with pharmacologic reperfusion Rethrombosis: Prevented by antiplatelet and anticoagulant Rx Full flow Ideal goal of pharmacologic reperfusion Dr S A Merchant
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99.
100. When patients present to a primary unit withoutinterventional capabilities:Therapeutic options a) lytics b) “transfer” to a facility with acardiaccath lab (with or without adjunctive therapy – “facilitated PCI”). Any such “transfer” needs to be effected rapidly to take advantage of the early benefits of revascularization. Dr S A Merchant
101. ‘Best of both worlds’ : Local rapidThrombolysisto majority & PCI Routinely Dr S A Merchant
106. This suggests that transfer to PCI centers should be initiated immediately after fibrinolysis without waiting to see whether reperfusion is successful or not. Dr S A Merchant
108. direct stenting in acute MI 26.9% 11.7% angioendpoint slow flow (TIMI 3 2) 12.5% 2.9% direct stenting n 102 pre- dilatation n 104 p=0.01 p=0.02 26.9% 12.5% 7.6% 6.7% 3.8% 3.8% 6.7% 11.7% 2.9% 4.9% 3.9% 0.9% 2.9% 8.8% angioendpoint slowflow (TIMI 3 2) no-flow (TIMI 0-1) distal embolization clinicaloutcomes (6-m F/U) death re-MI TVR C. LOUBEYRE et al. JACC 2002;39:15-21
109. cooling n 21 control n 21 10% % LV % pts 10 10 8% 5 5 2% 0% 0 0 median infarct size MACE endovascularcooling COOL-MI n 400 pts SR DIXON. JACC 2002;40:1928-34
110. X-SIZER• ANGIOJET EXPORT CATHETER PERCU-SURGE FILTER-WIRE thrombectomy distal protection device mechanism new cathether-based techniques X-AMINE AIMI EMERALD CRTs in AMI N 200 N 500 PROMISE N 200 Dr S A Merchant
111. RECOMMENDATION Task Force ESC 2005 guideline Routine Coronary Angio & PCI, if applicable, in successful Thrombolysis: 1 A LYSE NOW, STENT LATER !! Dr S A Merchant
112. Despite the clinical superiority of PAMI, thrombolytic therapy is the default treatment in many countries due to the practical limitations of PAMI Dr S A Merchant
113.
114. PCI is superior as per data but not practical and feasible, not only in India but also all over worldDr S A Merchant
115.
116. New emerging post fibrinolysis PCI has emerged as an alternative method of treatment that appears to be safer &better as compared to PAMIDr S A Merchant
122. CAPTIM – PrehospitaltPAvs 1°PCI1 Year Results Incidence of Shock P=0.09 Pre Hospital Lysis Primary PCI Death at 1 Year P=0.27 Pre Hospital Lysis Primary PCI Bonnefoy Lancet 2002 Dr S A Merchant
123. OPEN ARTERY THEORY: Better flow in the infarct artery improves survival Mortality at 42 Days TIMI 0 Complete occlusion TIMI 1 Penetration of obstruction by contrast but no distal perfusion TIMI 2 Perfusion of entire artery but delayed flow TIMI 3 Full perfusion, normal flow P < 0.005 TIMI 1 Chesebro JH et al. Circulation 1987;76:142-54
124. Full-Dose TNK 3-12h Before PCI: GRACIA-2 Characteristic TNK+PCI PCI No. patients 103 102 TIMI flow grade 3 59%* 43% Complete STRes (6h) 61%* 43% Death, MI, RI-UR 9% 12% Major bleeding 2% 3% No differences in infarct size, LV function *p < 0.05 Aviles ESC 2003 Dr S A Merchant
125. n 3200 patients occluded IRA (TIMI 0,1) randomization PCI (3-28 days after MI) + risk factor modification no PCI ASA -blockers ACE inhibitors Occluded Artery Trial (OAT) multicenter, randomized, controled 1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years
126. Apoptotic Rate in Occluedvs Open IRA Abbate A et al. Circulation 2002
138. Intracoro NTG/NicorandilThis makes sense to everyone – patient, relations, family doctor, consultant physician, interventional cardiologist. Also, both short term & long term clinical trials show excellent result with pharmacoinvasive approach in terms of reduce mortality, re-infarction & overall preservation of LV function Dr S A Merchant
139. Rescue PCI, Cardiogenic shock PCI, Facilitated PCI, Elective PCI are special subsets where clinician discretion is required Dr S A Merchant LONG DIFFUSE STENOSIS