STEMI – My Approach 2010
- 1. STEMI – My Approach2010Dr S A MerchantInterventional CardiologistDM MD DNB FSCAI Lilavati, CritiCare, BSES, Breach Candy Hospitals
- 2. Clinical manifestations of arterial thrombosisUA/NQMI:Partially-occlusive thrombus (primarily platelets)ST MI:occlusive thrombus (platelets, red blood cells, and fibrin)Intra-plaque thrombus (platelet dominated)Plaque coreIntra-plaque thrombus (platelet dominated)Plaque coreSUDDEN DEATHAdapted from Davies MJ. Circulation. 1990; 82 (supl II): 30-46.Dr S A Merchant
- 3. Initial Diagnosis of STEMIDr S A Merchant
- 4. 68%60402018%14%0<50%50%–70%>70%% StenosisSmall, vulnerable plaques are responsible for causing MIMI Patients (%)Falk et al: Circulation 1995;92:657–671Dr S A Merchant
- 5. MANAGEMENT OF Acute Myocardial InfarctionTHE IMPACT OF MEDICAL THERAPY% MortalityDefibrillation,Hemodynamic monitoringBeta BlockadeThrombolysis/adjuct therapyPTCA, StentDr S A Merchant
- 6. Hospital fibrinolysis: Door–to–needle ≤ 30 minNot PCIcapableCall 9-1-1Call fastInter-hospitaltransferEMS on sceneEncourage 12-lead ECGs
- 7. Consider prehospital fibrinolytic if capable and EMS–to–needle within 30 minOnset of symptoms of STEMI9-1-1EMSdispatchEMS triage planPCIcapableGOALS5 min8 minEMS transportPatientEMSPrehospital fibrinolysisEMS–to–needle≤ 30 minEMS transportEMS–to–balloon ≤ 90 minPatient self-transport Hospital door–to–balloon ≤ 90 minDispatch1 minTotal ischemic time: within 120 min“Golden Hour” = 1st 60 minTransport of Patients With STEMI and Initial Reperfusion TreatmentJ Am CollCardiol. 2004;44:671; Circulation. 2004;110:588.
- 8. Thrombolysis Versus Primary PCI - Time DependancyAbsolute 35 day mortality reduction v treatment delayN=50246Primary PCIBoersma et al, Lancet 1996 348:771Dr S A Merchant
- 9. Primary PCIangioplasty vsthrombolysisDr S A Merchant
- 10. PerCutaneous Interventions following AMI : A variety !!Dr S A Merchant
- 11. Primary PCIPOBA vs StentDr S A Merchant
- 12. primary PTCA vs stent6-month outcomesstentPTCAOR (95% CI)3.3%1.7%4.9%8.3%13.7%3.8%3.0%6.8%18%25.9%deathreMIdeath/ reMITVRdeath/reMI/TVR0.85 (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)00.51.512stentbetterPTCA betterDr S A Merchant
- 13. Real world situation: Door to balloon times in USAN=365N Engl J Med 2006;355Dr 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. Door to Balloon minus Door to Needle time Anticipated delay between door to balloon minus door to needle time if more than one hour , then thrombolysis is a better strategy.
- 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 PCIPre hospital lysisEURO-PCR Paris 2003Dr S A Merchant
- 18. French USIC 2000 survey: real worldUSIC. Circulation 2004;110:1909-1915Dr S A Merchant
- 19. Fibrinolysis vs Transfer for PCIPre HospPrimaryIn HospLysisPCILysisCAPTIM CAPTIM DANAMI 2 DANAMI 2Death (%) 3.8 4.8 6.6 7.61yr 5.4 7.3Reinfarction (%) 3.7 1.7 1.6 6.3Disabling CVA (%) 1.0 0.0 1.1 2.0Any of Above (%) 8.2 6.2 8.0 13.7*(* P < 0.003)VahanianESC, 2002Dr S A Merchant
- 20. Pre Hospital thrombolysisCAPTIM 1 Year Results (TNK)Sx < 2 hoursDeathP=0.057Pre HospitalLysisPrimaryPCIGW Symposium, AHA 2002Dr 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 flowsGibson : Circulation 2000;101-125Improved flows
- 22. PTCA vsFibrinolysis:Short Term Clinical Outcomes (23 RCTs)PTCA P<0.0001Fibrinolysis P<0.0001Frequency (%)P=0.0002P=0.0003P<0.0001P=0.032P=0.0004P<0.0001DeathDeath, no SHOCKdataReMIRec. IschTotal StrokeHem. StrokeMajor BleedDeathMICVAN = 7739Keeley E. et al., Lancet 2003; 361:13-20.
- 23. Is timing an issue even for Primary PCI?Dr S A Merchant
- 24. Survival Benefit by Time to Treatment with LyticsDr S A Merchant
- 25. Dr S A Merchant
- 26. NRMI-2 : 27080 consecutive patients24%% of patients 21%20%2017%1510%108%50min<6060-90120-15090-120150-180>180C.P. CANNON. JAMA 2000;283:2941-7door-to-balloon times in primary PCIDr S A Merchant
- 27. Mortality by time to reperfusion with Primary PCINRMI-2 Registry (27,080)C.P. CANNON. JAMA 2000;283:2941-7Dr S A Merchant
- 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 reperfusionCardiac rupture is more likely to occur as the time to lysis increasesDr S A Merchant
- 31. RecommendationsWhen performed by experienced* operators/centers, PCI is the reperfusion strategy of choice for patients with AMI
- 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 / yearDr S A Merchant
- 33. After 12 hours???BRAVE-2Rationale: 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 2005Dr S A Merchant
- 34. Role of PCI in the management of STEMIagenda primary PCI
- 35. primary PCI - angioplasty vsthrombolysis- added benefit of stent placementtiming- culprit vessel vs all vessel interventionrole of 2b/3a inhibitors
- 36. transfer, rescue and facilitated PCI
- 37. the challengeshow to achieve optimal reperfusionwhat to do with the occluded IRAreplacing the function of death cellsDr S A Merchant
- 38. Dr S A Merchant
- 39. culprit vessel vs all vessel interventionThe ACC/AHA guidelines on PCI give elective PCI of a non-infarct related artery at the time of AMI a class III recommendation with a C level of evidence.
- 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
- 41. Role of GP 2b/3a inhibitorsDr S A Merchant
- 43. GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization30%PlaceboGP IIb/IIIa26.1%20%14.6%11.2%9.7%10%6.8%6.0%5.8%4.5%4.5%2.0%p = 0.06p = 0.01p = 0.03p = 0.03p = 0.020%CADILLACEPICRAPPORTNeumannADMIRAL N: 64 483 200 300 2082
- 46. Types of ThrombolyticsA. Clot Selective / Clot-Binding / fibrin SpecificB. Non clot Selective/ Non–Clot-Binding / Non Fibrin SpecificDr S A Merchant
- 47. Clinical Relevance of Fibrin AffinityAction of Non–Clot-Binding AgentsAction of Clot-Binding Agents(Urokinase, Streptokinase)(Alteplase, Tenecteplase)Clot-BindingPlasminogenActivatorsClotBlood VesselNon–Clot-BindingPlasminogenActivatorsClotBlood VesselDr S A Merchant
- 49. Streptokinase
- 50. AnisoylatedPlasminogen Streptokinase Activator Complex
- 51. Fibrin-Specific
- 52. Recombinant tissue plasminogen activator (rt-PA)
- 53. Mutants and Variants of Tissue-type Plasminogen Activator
- 54. TNK-rt-PA
- 55. Reteplase
- 56. Lanetoplase
- 57. Single-chain Urokinase-type Plasminogen Activator
- 59. StaphylokinaseDr S A Merchant
- 62. Comparison with StreptokinaseDr S A Merchant
- 63. Dr S A Merchant
- 64. Dr S A Merchant
- 65. Dr S A Merchant
- 66. total5286.7%11.5%0.55 (0.30-1.01)p=0.052rescue PCIshort termoutcome: deathodds ratio (95% CI)n PCI cons.0.13 (0.01-1.40)BelenkieRESCUEPRAGUEVermeer281512001496.3%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)00.51.512.0Dr S A Merchant
- 67. Incidence of ShockP=0.09Pre HospitalLysisPrimaryPCICAPTIM – PrehospitaltPAvs 1°PCI1 Year ResultsDeath at 1 YearP=0.27PrimaryPCIPre HospitalLysisBonnefoy Lancet 2002Dr S A Merchant
- 68. Tenecteplase is the lytic of choiceCantor also emphasized that previous trials have used different lytics and no clopidogrel preloading.
- 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
- 71. Dr S A Merchant
- 76. ExTRACT TIMI 25Net Clinical Benefit at 30 DaysUFH (%)Enox (%)RRR (%)Death / Nonfatal MI / Nonfatal Disabling Stroke 10.11812.3Death / Nonfatal MI / Nonfatal Major Bleed 11.01412.8Death / Nonfatal MI / Nonfatal ICH 10.11712.2Enox BetterUFH BetterRRDr S A Merchant
- 82. CLARITY–TIMI 281° Endpoint:Occluded Artery (or D/MI Thru Angio/HD)36% odds reductionOdds ratio 0.64(95% CI, 0.53 – 0.76)P < 0.001Occluded artery or death/MI (%) n = 1,752 n = 1,739 | | | | | | 0.4 0.6 0.8 1.0 1.2 1.6Clopidogrel Placebo LD 300 mg MD 75 mgClopidogrel Placebo better betterSabatine MS, N Engl J Med. 2005;352:1179-1189.Dr S A Merchant
- 83. 1098765432100 7 14 21 28COMMIT: Effect of Clopidogrel on Death InhospitalPlacebo + 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 givenTime since randomization (days)Chen ZM, et al. Lancet. 2005;366:1607-1621.Dr S A Merchant
- 84. SummaryAcute therapy in STEMI focuses on reperfusion & antithrombotic therapy
- 85. Reasonable options for hospitals without onsite PCI capability
- 86. Fibrinolytic Therapy (goal : door to needle time ≤ 30 minutes)
- 87. Transfer for Primary PCI (goal: door to balloon time ≤ 90 minutes)
- 88. Transfer for Rescue PCI if reperfusion with lytic fails
- 89. Facilitated PCI : no clinical benefit seen to date
- 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. Summary (cont.)Current ACC/AHA STEMI guidelines recommend IV UFH as ancillary therapy to reperfusion therapy
- 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)
- 95. Fondaparinux was not superior to UFH is Stratum 2 of OASIS 6 for STEMI
- 96. Long term treatment involves aggressive multifactorial lifestyle modification & both antithrombotic & anti ischemic therapiesDr S A Merchant
- 97. PCI p lyticPharmacoinvasive approachPartial flowComplete obstructionPartial success withpharmacologicreperfusionRethrombosis:Prevented by antiplatelet and anticoagulant RxFull flowIdeal goal ofpharmacologicreperfusionDr S A Merchant
- 98. ACC/AHA Guidelines for Management of Patients With STEMI, 2004 Reperfusion Options for STEMI PatientsIf presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy.Fibrinolysis generally preferred Early presentation ( ≤ 3 hours from symptom onset and delay to invasive strategy)Invasive strategy not an option Cath lab occupied or not available Vascular access difficulties No access to skilled PCI labDelay to invasive strategy Prolonged transport Door-to-balloon more than 90 minutes > 1 hour vsfibrinolysis (fibrin-specific agent) nowACC/AHA Guidelines for Management of Patients With STEMI,Journal of the American College of Cardiology 2004Dr S A Merchant
- 99. Emerging ModalitiesPharmacoinvasive Management (PCI following TNK) is a better , safer option than PAMI as proved recently . It widens the time window for PCIThis seems to combine the benefits of Mechanical and pharmacological strategies in reperfusionJACC Sept 2007Dr S A Merchant
- 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 RoutinelyDr S A Merchant
- 103. Standard treatment after fibrinolysis (rescue PCI for failed reperfusion, with elective PCI encouraged for successfully reperfused patients after 24 hours)Pharmacoinvasive strategy (transfer for PCI within six hours of fibrinolysis).Both groups received TenecteplaseDr S A Merchant
- 104. TRANSFER-AMI:30-Day Primary End Point and ComponentsDr S A Merchant
- 105. TRANSFER-AMI:STEMI to centers without timely access to a catheterization labpharmacoinvasiveapproach consisting of full-dose thrombolytics, followed by emergent transfer for cardiac catheterization within 6 hours, is safe and efficacious compared to treatment with thrombolytics and transfer for rescue PCI only.
- 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
- 107. TRANSFER-AMI:30-Day Bleeding End PointsDr S A Merchant
- 108. direct stenting in acute MI26.9%11.7%angioendpointslow flow (TIMI 3 2)12.5%2.9%directstentingn 102pre-dilatationn 104p=0.01p=0.0226.9%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%angioendpointslowflow (TIMI 3 2) no-flow (TIMI 0-1) distal embolizationclinicaloutcomes (6-m F/U)death re-MI TVRC. LOUBEYRE et al. JACC 2002;39:15-21
- 109. cooling n 21 control n 2110%% LV% pts10108%552%0%00median infarct sizeMACEendovascularcoolingCOOL-MI n 400 ptsSR DIXON. JACC 2002;40:1928-34
- 110. X-SIZER•ANGIOJETEXPORT CATHETERPERCU-SURGEFILTER-WIREthrombectomydistal protectiondevicemechanismnew cathether-based techniquesX-AMINEAIMIEMERALDCRTs in AMIN 200N 500PROMISEN 200Dr S A Merchant
- 111. RECOMMENDATIONTask Force ESC 2005 guidelineRoutine Coronary Angio & PCI, if applicable, in successful Thrombolysis: 1 ALYSE 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 PAMIDr S A Merchant
- 113. ConclusionIn Indian context – Thrombolysis is the commonly accepted method of treatment in STEMI
- 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. New TNK is an ideal , novel thrombolytic agent, IV bolus reduces door to needle time and higher TIMI III and II flow( 86%)
- 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
- 117. API GuidelinesIndications for thrombolytic therapyEarly presentation (3 h or less from symptom onset and delay to invasive strategy)
- 118. Invasive strategy is not an option- Catheterization laboratory not available / occupied.- Financial reasons- Lack of access to a skilled PCI laboratory- Vascular access difficultiesDelay to invasive strategyProlonged transport (Door-to-Balloon)- (Door-to-Needle) time > 1 hour.Medical contact-to-balloon or door-to-balloon time > 90 minutesDr S A Merchant
- 119. ELAXIM INDIAN REGISTRYDr S A Merchant
- 120. ELAXIM INDIAN REGISTRY* ICH = Intracranial hemorrhageDr S A Merchant
- 122. CAPTIM – PrehospitaltPAvs 1°PCI1 Year ResultsIncidence of ShockP=0.09Pre HospitalLysisPrimaryPCIDeath at 1 YearP=0.27Pre HospitalLysisPrimaryPCIBonnefoy Lancet 2002Dr S A Merchant
- 123. OPEN ARTERY THEORY:Better flow in the infarct artery improves survivalMortality at 42 DaysTIMI 0 Complete occlusionTIMI 1 Penetration of obstruction by contrast but no distal perfusionTIMI 2 Perfusion of entire artery but delayed flowTIMI 3 Full perfusion, normal flowP < 0.005TIMI 1Chesebro JH et al. Circulation 1987;76:142-54
- 124. Full-Dose TNK 3-12h Before PCI: GRACIA-2Characteristic TNK+PCI PCINo. patients 103 102TIMI 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 < 0.05Aviles ESC 2003Dr S A Merchant
- 125. n 3200 patientsoccluded IRA (TIMI 0,1)randomizationPCI (3-28 days after MI) + risk factor modificationno PCIASA-blockersACE inhibitorsOccluded Artery Trial (OAT)multicenter, randomized, controled1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years
- 126. Apoptotic Rate in Occluedvs Open IRA Abbate A et al. Circulation 2002
- 127. open questions on infarct/necrotic tissuehazards of stem cell manipulation
- 128. arrhythmogenic potential of implanted cells
- 129. economic issues
- 130. the capacity of the stem cells to find their optimal myocardial ‘niche’
- 131. long-term fate of transplanted cells in the recipient heart
- 132. optimal timing for transplantationDr S A Merchant
- 133. Take Home Message:Optimum management of STEMI – A PharmacoInvasive ApproachInitial Fibrinolysiswith t-PA within 30-60 mins of chest pain in ambulance, nursing home, non-PCI hospital
- 134. Endovascular cooling: Aspirin, loading dose clopidogril/prasugrel, InjEnoxyparin, GpIIb/IIIa Inhibitor, nitrates, Ace-Inhibitors, beta blocker, diltiazem, high dose statins, trimatazione, sedationDr S A Merchant
- 135. Transfer patient within 6 hours to PCI centre forCor angiography
- 136. Thrombectomy: Suction by Export Cath, AngioJet
- 137. Direct stenting
- 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 MerchantLONG DIFFUSE STENOSIS
- 140. HOW FAST SHOULD WE GO ? QUICKER IS BETTER THANK YOU