Facilitated PCI & rescue PCIDolly mathew

Primary PCI is the preferred reperfusion strategy in STEMIMost patients donot arrive at the PCI center within the 90mts of FMCIf delay is expected, timely thrombolysis , followed by early transfer for PCICombined reperfusion strategies include facilitated pci, pharmacoinvasive therapy,rescue pci

Facilitated PCIStrategy of thrombolysis immediately followed by PCI with a planned door to balloon time 90- 120 mts in pts with STEMI

Reduction in ischemia time, earlier reperfusion,higher TIMI III flow in the occluded artery, with facilitation of guidewire or balloon passage, decreased clot burden, lower incidence of distal embolizationFull / half dose thrombolysis , half dose thrombolysis with GPIIb/IIIa antagonistsAddresses the value of pre treatment with thrombolytics in patients otherwise eligible for primary pci

Pharmacoinvasive therapyGiving T lysis at a non PCI center, transfer the pt to PCI center, performed within 2- 24 hrs within Tlytic therapy, regardless of whether Tlysis results in successful reperfusion

Time to PCI is longer than facilitated PCI

Routine early PCI after Tlysis in pts who are not eligible for primary PCI

Rescue PCI PCI performed urgently if Tlysis fails -Persistant hemodynamic or electrical instability -Persistant ischemic symptoms -Failure to achieve 50-70% ST resolution at 90mts after infusion started

Timing of PCI

Trials reviewed - facilitated PCI

GRACIA 2002N50030 day resultsEarly post t lysis PCIVsRoutine drug treatmentEarly intervention supr to drug treatmentCAPITAL AMI 2004 N 17030 day resultsCombined angioplasty + pharmacologic treatmentVsthrombolysis

Primary end point sig reduced in combination groupFINESSE 2004N 245290 day resultsPrimary PCIFacilitated PCI with abciximabFPCI with reteplase or abciximabNo significant difference in end pointsASSENT- 4 PCI838/829Std PCI Tenecteplase + PCIPrematurely terminatedBRAVE N 253 Half dose reteplase + abciximab / abciximab alone + PCINo diff in the post pci TIMI flowMajor bleeding more in combination group

PCI immediately after thrombolysis-GRACIA 2002 (Group analysis of a/c IHD ) lancet

500 AMI pts, 23 centers in Spain and Portugal, the 30-day results - early interventional strategy within 24 hours of thrombolysis , followed by stent implantation - post thrombolysis classical drug-based treatment

Early intervention may be superior to medical therapy in AMIReduction in inhospital ischemia driven revascularisation- 2% vs 12% ( p

Combined angioplasty & pharmacological intrvention vs thrombolysis in AMI - CAPITAL AMI ;jacc2004 trial170 high-risk MI patients within 6 hrs of symptom onsetthrombolysis alone with full-dose tenecteplase or thrombolysis with full-dose tenecteplase followed by immediate transfer for CAG and possible PCI (combination group)Pts with failed thrombolysis also referred for CAG &possible intervention

The primary end point of the study was a composite of death/MI/stroke/recurrent ischemia at 30 days, which was significantly reduced in the combination groupMajor bleeding was not significantly different between the two groups

Major efficacy results in CAPITAL-AMI LeMay M. American College of Cardiology 2004 Scientific Sessions; Mar 7-10, 2004; New Orleans, LA.

End point Thrombolysis alone Thrombolysis plus immediate transfer for angiography/PCI Significant Death/MI/stroke/recurrent ischemia (%) 21.4 9.3 Yes (p=0.034) Death (%) 3.6 2.3 No MI (%) 11.9 4.7 No Stroke (%) 1.2 1.2 No Recurrent ischemia (%) 17.9 7.0 Yes (p=0.037)

GRACIA 2 trial 2003212 pts,AMI

BRAVE trial Baverian Reperfusion Alternative Evaluation 253 pts , 12 hrs of symptom onset to facilitated PCI Half dose reteplase + abciximab or abciximab alonePrimary endpoint infarct size estimation by SPECT at 5-10 days after randomizationHigher incidence of TIMI III flow in the infarct occluded artery in the reteplase plus abciximab group than in the abciximab group alone (40% vs 18%, p

Tirofiban given in the emergency room before angioplasty( TIGER- PA) pilot study- circulation 2003100 acute MI pts, within 12 hrs of symptom onsetTirofiban in the emergency dept / cath labEarly administration asso with improvement in the initial TIMI flow gradeEarly administration of of tirofiban is feasible & safe , it improved the angiographic outcome in in pts with AMI undergoing PCI30 day incidence of MACE suggested by early administration of tirofiban beneficial

Ongoing tirofiban in myocardial infarction evaluation trial( On- TIME)507 pts with AMI , transferred to pci center, randomized to early prehospital initiation or late cath lab initiaition of tirofibanPrimary end point, TIMI iii flow at initial angio did not differ significantly between the 2 groups ( 19 vs 15%, p0.22)Thrombus or fresh occlusion 60%vs 73% , p0.00230 day death 3.7% vs 0.8%1yr mortality 4.5vs 3.7%, p 0.66Despite lower prevalence of thrombus or fresh occlusion, early initiation of tiro was not asso with beneficial effects in the post pci angiographic or 1yr clinical outcome

Facilitated intervention with enhanced reperfusion to stop events FINESSE trial Am heart j 2004(-ve results)2452 pts, 3 arm study, double blind , 6hrs of pain onset , estimated time to cathlab 1-4 hrs, door to balloon 132mts -Primary PCI - Facilitated PCI with abciximab alone - Facilitated PCI with reteplase/abciximabPrimary endpoint:Composite at 90 days of all-cause mortality/re hospitalization for CCF, resuscitated VF more than 48 hours after randomization & cardiogenic shockSecondary endpoints:Complications of MI through 90 daysRe hospitalization for congestive heart failureResuscitated ventricular fibrillationCardiogenic shock

FINESSE Conclusions

No significant improvement in the 1 endpoint in pts treated with either abciximab-facilitated PCI or reteplase/abciximab-facilitated PCI compared with primary PCI with administration of abciximab in the cath labReteplase/abciximab administered early was associated with an increase in pre-PCI TIMI 3 flow and > 70% ST-segment resolution at 60-90 minutesPost-PCI TIMI 3 flow and ST resolution at 180-240 minutes was similar in all 3 treatment groups

FINESSE ConclusionsSignificant increase in major and minor bleeding complications in the facilitated PCI groupsNo increase in total stroke rateAn increase in the rate of intracranial hemorrhage in the reteplase / abciximab group

Therefore, primary PCI with in-lab abciximab administration provides better benefit/risk profile than the 2 facilitated strategies in patients with STEMI who can undergo PCI within 4 hours of first medical contact

FINESSE before pciAfter pci

FINESSE subgroup analysis60% pts entered in pci hospitalsAnalysis of pts with TIMI score 3, within 4hrs of symptom onset had a reduction in ischemic events with facilitated strategyThus, for pts seen 2-3 hrs of symptom onset, immediate thrombolysis recommended , if PCI likely to be delayed

Assessment of safety & efficacy of a new treatment strategy for AMI -4 (ASSENT-4)trial lancet2006(-ve results in facilitated PCI)Randomized trial , 6 hrs of symptom onset, who were scheduled to undergo pci after a delay of 1-3 hrs, who were assigned to std pci(n- 838), pci preceded by full dose tenecteplase(n 829) ; door- balloon- 110mtsPremature termination higher inhospital mortality in facilitated pci group1 end point achieved in 19% in facilitated 13% in the std pci group(RR=1.39,95% CI:1.11-1.74;P.0045)Inhospital stroke 1.8 vs 0%,p

ASSENT-4Strategy of facilitated pci consisting of full dose thrombolysis plus anti thrombotic co therapy & preceding pci by 1-3 hrs was associated with worse clinical outcome than primary pci alone & cannot be recommended - Absence of heparin infusion, clopidogrel loading, prohibition of routine use of GP IIbIIIa antagonists - Delay in thrombolytic therapy

Subgroup analysis -ASSENT 445% pts enrolled in the PCI hospitals with a minimal pci related delay timeThese pts had a worst outcome with facilitated strategyIn contrast, pts who had a short time pain onset to thrombolysis(2-3hrs), who were given prehospital thrombolysis, had a trend towards better outcome with facilitated pci

Meta analysis by Keeley & coworkers , 17 trials , lancet 2006Facilitated pci (n- 2237) was associated with significantly worse short term outcomes( upto 42 days) than primary pci (n- 2267)aloneDeath 5% vs 3%Nonfatal MI 3% vs 2%Urgent target vessel revas 4% vs 1%Major bleeding 7% vs 1%Total stroke 1.1% vs 0.3%Increased rates of adverse events observed mainly when thrombolytic therapy was used to facilitate pci

Pharmacoinvasive trials

CARESS IN AMI297/300Facilitated pciVsMedical/ rescueCombined end point lower in facilitated pciWEST 304Early fibrinolyticsWith or withoutRoutine rescue/ early invasivevs primary pci Similar end pointsTRANSFER AMI1059TNK immediate pciTNK rescue pciCardiovascular events lower in the pharmacoinvasive group compared with std care & rescue pci

The Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) pharmacoinvasive compared a strategy of early transfer of patients to a PCI center after thrombolysis vs medical treatment continued in the admitting hospital and transfer for rescue PCI only if there was evidence of lack of reperfusion Patients less than 12 hours from symptom onset and with STEMI were randomized to either -- Facilitated PCI (lytics and transfer to the nearest PCI center) -- Medical treatment/rescue (lytics and transfer for rescue PCI if persistent ST elevation)

600 patients were randomized to facilitated PCI (n = 297) or to the medical/rescue (n = 300) arms of the study time from pain onset to reteplase treatment was 169-171 minutes time from reteplase administration to PCI was 136 mts in the facilitated arm vs 212 mts in the rescue armThe combined endpoint of death/reinfarction/refractory ischemia at 30 days was significantly lower in the facilitated arm compared with the medical/rescue-treated patients (4.1% vs 11.1%, respectively;P= .001)

Outcome Immediate PCI (%) Rescue PCI (%) pDeath, re-MI, refractory ischemia at 30 days* 4.4 10.7 0.004Major bleed3.4 2.3 0.47 Stroke 0.7 1.3 0.50

The WEST (Which Early ST-Elevation Myocardial Infarction Therapy) trial304 patients -- fibrinolytic therapy at the earliest contact (prehospital or in referral hospital, with clopidogrel and enoxaparin) with/without routine rescue or early invasive therapy -- primary PCITenecteplase and enoxaparin followed by routine early invasive therapy had similar death and MI rates to primary PCI This supports the need for further trials to assess the role of optimal early fibrinolytic therapy (including prehospital) and antithrombotic therapy versus primary PCI in settings where very rapid PCI is not available

Routine angioplasty after thrombolysis for AMI: TRANSFER-AMI nejm20091059 pts with high risk STEMI, at non PCI centerFull dose tenecteplase immediate transfer for PCI tenecteplase transfer for rescue PCIMedian time for PCI 3.9 hrs(2-6hrs)

Inclusion Criteria TRANSFER AMIWithin 12 hrs of symptom onset 2 mm ST-segment elevation in 2 anterior leads OR 1 mm ST-segment elevation in 2 inferior leads and at least one of the following:SBP < 100HR > 100Killip Class II-III 2mm ST-segment depression in anterior leads 1 mm ST-segment elevation in V4R

Selected Exclusion CriteriaCardiogenic ShockPCI within 1 monthPrevious CABGPrimary PCI available with DTB < 60 minutesUse of Enoxaparin in last 12 hours in patient > 75 years of ageConsent not obtained within 30 minutes of TNK

ProceduresCardiac Cath performed (%) Time- TNK to Cath (hrs)PCI performed (%) Stent used (% of PCI cases) Time- TNK to PCI (hrs) PCI within 6 hrs of TNK (%) PCI within 12 hrs of TNK (%) GP IIb/IIIa inhibitor use (%) Time- TNK to GP IIb/IIIa inhib. (hrs) IABP use (%)CABG performed (%)Standard Treatment(n=508)8227 (4, 69)629818 (4, 73)38475311 (4, 63)68PharmacoinvasiveStrategy(n=522)973 (2, 4)84984 (3, 5)8997734 (3, 5)76

02468101214161805101520253010.616.6Days from Randomization% of Patientsn=496n=508422468415466415463414461414460412457Primary Endpoint: 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia, Shock OR=0.537 (0.368, 0.783); p=0.0013

Components of Primary Endpoint

DeathReinfarctionRecurrent IschemiaDeath/MI/IschemiaNew / worsening CHFCardiogenic ShockStandard Treatment(n=498)3.66.02.211.75.22.6PharmacoinvasiveStrategy(n=512)3.73.30.26.52.94.5

P-Value

0.940.0440.0190.0040.0690.11

SummaryCompared with Standard Treatment, a Pharmacoinvasive Strategy of routine early PCI within 6 hrs after thrombolysis is associated with a 6% absolute (46% relative) reduction in the composite of death, reinfarction, recurrent ischemia, heart failure and shockThe pharmacoinvasive strategy is not associated with any increase in transfusions, severe bleeding or intracranial hemorrhage despite high use of GP IIb/IIIa inhibitors during PCIIn contrast to older trials, routine early PCI after thrombolysis using stents and contemporary pharmacotherapy is safe and effective

ConclusionsFor high-risk STEMI patients receiving thrombolysis at non-PCI centres, urgent transfer and PCI within 6 hours is associated with significantly less ischemic complications and no excess in bleedingTransfers to PCI centres should be initiated immediately after thrombolysis without waiting to see whether reperfusion is successful

Rescue trials

trialcomparisonPatient groupMERLIN 2004N 153/15430 day follow upCAG rescue pciVsConserv mgtSTEMI , failed tlysis

REACT 2005N 144/1416months follow upRescue pciVs Rpt t lysis orConserv mgtSTEMI , failed reperfn, within 90mts after lytic treatment

STOPAMI 2004N 90/ 91SI 7-10 days apart1yr follow upStenting VsBalloon angioplastySTEMI ,failed thrombolysisTIMI flow grade 2 at CAG

Middlesbrough early revascularization to limit infarction MERLIN trial JACC 2004307 patientsDidnt improve survival at 30 daysImproved event free survivalMore strokes, more bleeding complicationsDidnt result in preservation of LV systolic function at 30 days

MERLIN TRIAL end points

Rescue angioplasty vs conservative treatment or repeat thrombolysis REACT trial, nejm2005427 patientsPrimary end points significantly reduced in rescue group

Coronary stenting vs balloon angioplasty as a rescue intervention after failed thrombolysis in pts with AMI STOPAMI 4 trial JACC 2004181 patients,after failed thrombolysis, within 24 hrs(TIMI flow 2during CAG )Coronary stenting 90 patientsBalloon angioplasty in 91 patientsSalvage index ( proportion of initial perfusion defect salvaged by rescue intervention) obtained by paired scintigraphic studies performed 7-10 days apart was the primary end point

Myocardial salvage index was significantly greater in the stent group (.35 vs .25,p .005) than in angioplasty groupNo difference in the major bleeding1yr mortality was 8% vs 12%Pts with AMI, failed thrombolysis benefit from rescue mechanical reperfusion in terms of myocardial salvageStenting asso with greater myocardial salvage than balloon angioplasty group

Meta analysis of rescue PCI trials Reduction in heart failure, reinfarction & a trend towards lower mortality rate with rescue PCI

Another meta analysis of 5 randomized trials- -36% reduction in risk of death, 28% reduction in the risk of heart failure, compared with the conservative group

Reperfusion strategy

For patients presenting with high risk STEMI, who cannot undergo timely primary PCI , best approach would be pre hospital thrombolysis, or local thrombolysis at non PCI hospitals, followed by transferring the patient for PCI

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