Facilitated PCI & rescue PCI

Dolly mathew

• Primary PCI is the preferred reperfusion strategy in STEMI

• Most patients donot arrive at the PCI center within the 90mts of FMC

• If delay is expected, timely thrombolysis , followed by early transfer for PCI

• Combined reperfusion strategies include facilitated pci, pharmacoinvasive therapy,rescue pci

Facilitated PCI

• Strategy 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 embolization

• Full / half dose thrombolysis , half dose thrombolysis with GPIIb/IIIa antagonists

• Addresses the value of pre treatment with thrombolytics in patients otherwise eligible for primary pci

Pharmacoinvasive therapy

• Giving 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 results

Early post t lysis PCIVsRoutine drug treatment

Early intervention supr to drug treatment

CAPITAL AMI 2004 N 17030 day results

Combined angioplasty + pharmacologic treatmentVsthrombolysis

Primary end point sig reduced in combination group

FINESSE 2004N 245290 day results

Primary PCIFacilitated PCI with abciximabFPCI with reteplase or abciximab

No significant difference in end points

ASSENT- 4 PCI838/829

Std PCI Tenecteplase + PCI

Prematurely terminated

BRAVE N 253

Half dose reteplase + abciximab / abciximab alone + PCI

No 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 AMI• Reduction in inhospital ischemia driven revascularisation- 2% vs 12%

( p<o.oo1)

• A combined therapy of stenting within 24 hours of thrombolysis results in shorter hospital stays and a lower risk of adverse events after discharge, compared with conventional drug therapy

Combined angioplasty & pharmacological intrvention vs thrombolysis in AMI - CAPITAL

AMI ;jacc2004 trial

• 170 high-risk MI patients within 6 hrs of symptom onset• thrombolysis 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 group

• Major bleeding was not significantly different between the two groups

Major efficacy results in CAPITAL-AMI 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)

LeMay M. American College of Cardiology 2004 Scientific Sessions; Mar 7-10, 2004; New Orleans, LA.

GRACIA 2 trial 2003

• 212 pts,AMI <12hrs -Primary PCI with abciximab -tenecteplase + enoxaparin followed by

CAG within 2-12 hrs & interventions if indicated

• No difference in the infarct size or LV function at 6 wks

• No difference in the major bleeding

BRAVE trial – Baverian Reperfusion Alternative Evaluation

• 253 pts , 12 hrs of symptom onset to facilitated PCI • Half dose reteplase + abciximab or abciximab alone• Primary endpoint – infarct size estimation by SPECT at 5-10 days after

randomization• Higher 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<0.001)

• No difference in the post PCI TIMI III flow (87.2% vs 86.7%, p 0.91) or infarct size (13% vs 11.5%)

• Major bleeding 5.6% (reteplase +abciximab) vs 1.6% (abciximab) , p o.16

• Within 6 months after randomization, the composite end point of death, recurrent MI, or stroke occurred in 6.4% pts vs 4.7%

Tirofiban given in the emergency room before angioplasty( TIGER- PA) pilot study- circulation 2003

• 100 acute MI pts, within 12 hrs of symptom onset• Tirofiban in the emergency dept / cath lab• Early administration asso with improvement in the

initial TIMI flow grade• Early administration of of tirofiban is feasible & safe ,

it improved the angiographic outcome in in pts with AMI undergoing PCI

• 30 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 tirofiban

• Primary 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% , p0.002• 30 day death 3.7% vs 0.8%• 1yr mortality 4.5vs 3.7%, p 0.66• Despite 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/abciximab• Primary endpoint: Composite at 90 days of all-cause

mortality/re hospitalization for CCF, resuscitated VF more than 48 hours after randomization & cardiogenic shock

• Secondary endpoints:• Complications of MI through 90 days

– Re hospitalization for congestive heart failure– Resuscitated ventricular fibrillation– Cardiogenic 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 lab

• Reteplase/abciximab administered early was associated with an increase in pre-PCI TIMI 3 flow and > 70% ST-segment resolution at 60-90 minutes

• Post-PCI TIMI 3 flow and ST resolution at 180-240 minutes was similar in all 3 treatment groups

FINESSE Conclusions

• Significant increase in major and minor bleeding complications in the facilitated PCI groups

• No increase in total stroke rate• An 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 pci

After pci

FINESSE subgroup analysis

• 60% pts entered in pci hospitals• Analysis of pts with TIMI score ≥3, within 4hrs

of symptom onset had a reduction in ischemic events with facilitated strategy

• Thus, 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- 110mts

• Premature termination – higher inhospital mortality in facilitated pci group

• 1° 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 <0.001• Higher incidence of re infarction(6 %vs 4% 0.0279), target

vessel revascularization (7% vs 3% p .0041)

ASSENT-4

• Strategy 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 4

• 45% pts enrolled in the PCI hospitals with a minimal pci related delay time

• These pts had a worst outcome with facilitated strategy

• In 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 2006

• Facilitated pci (n- 2237) was associated with significantly worse short term outcomes( upto 42 days) than primary pci (n- 2267)alone

• Death 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 AMI297/300

Facilitated pciVsMedical/ rescue

Combined end point lower in facilitated pci

WEST 304

Early fibrinolyticsWith or withoutRoutine rescue/ early invasivevs primary pci

Similar end points

TRANSFER AMI1059

TNK immediate pciTNK rescue pci

Cardiovascular 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 arm

• The 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 (%) p Death, re-MI, refractory ischemia at 30 days* 4.4 10.7 0.004Major bleed 3.4 2.3 0.47

Stroke 0.7 1.3 0.50

The WEST (Which Early ST-Elevation Myocardial Infarction Therapy) trial

• 304 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 PCI• Tenecteplase 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 –nejm2009

• 1059 pts with high risk STEMI, at non PCI center

• Full dose tenecteplase immediate transfer for PCI

• tenecteplase transfer for rescue PCI• Median time for PCI 3.9 hrs(2-6hrs)

Inclusion Criteria –TRANSFER AMI

• Within 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 < 100– HR > 100– Killip Class II-III– ≥ 2mm ST-segment depression in anterior leads– ≥ 1 mm ST-segment elevation in V4R

Selected Exclusion Criteria

• Cardiogenic Shock• PCI within 1 month• Previous CABG• Primary PCI available with DTB < 60 minutes• Use of Enoxaparin in last 12 hours in patient > 75 years of age• Consent not obtained within 30 minutes of TNK

Procedures

Cardiac 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)82

27 (4, 69)

62

98

18 (4, 73)

38

47

53

11 (4, 63)

6

8

Pharmacoinvasive

Strategy

(n=522)97

3 (2, 4)

84

98

4 (3, 5)

89

97

73

4 (3, 5)

7

6

0

2

4

6

8

10

12

14

16

18

0 5 10 15 20 25 30

10.6

16.6

Days from Randomization

% of Patients

Standard PCI > 24 hrs (n=496)Invasive < 6 hrs (n=508)

n=496n=508

422468

415466

415463

414461

414460

412457

Primary 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

Death

Reinfarction

Recurrent Ischemia

Death/MI/Ischemia

New / worsening CHF

Cardiogenic Shock

Standard

Treatment

(n=498)

3.6

6.0

2.2

11.7

5.2

2.6

Pharmacoinvasive

Strategy

(n=512)

3.7

3.3

0.2

6.5

2.9

4.5

P-Value

0.94

0.044

0.019

0.004

0.069

0.11

Summary

• Compared 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 shock

• The pharmacoinvasive strategy is not associated with any increase in transfusions, severe bleeding or intracranial hemorrhage despite high use of GP IIb/IIIa inhibitors during PCI

• In contrast to older trials, routine early PCI after thrombolysis using stents and contemporary pharmacotherapy is safe and effective

Conclusions

• For 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 bleeding

• Transfers to PCI centres should be initiated immediately after thrombolysis without waiting to see whether reperfusion is successful

Rescue trials

trial comparison Patient group

MERLIN 2004N 153/15430 day follow up

CAG± rescue pciVsConserv mgt

STEMI , failed tlysis

REACT 2005N 144/1416months follow up

Rescue pciVs Rpt t lysis orConserv mgt

STEMI , failed reperfn, within 90mts after lytic treatment

STOPAMI 2004N 90/ 91SI 7-10 days apart1yr follow up

Stenting VsBalloon angioplasty

STEMI ,failed thrombolysisTIMI flow grade ≤2 at CAG

Middlesbrough early revascularization to limit infarction – MERLIN trial JACC 2004

• 307 patients• Didn’t improve survival at 30 days• Improved event free survival• More strokes, more bleeding complications• Didn’t result in preservation of LV systolic function at 30 days

MERLIN TRIAL – end points

Rescue angioplasty vs conservative treatment or repeat thrombolysis – REACT trial, nejm2005

• 427 patients• Primary 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

2004

• 181 patients,after failed thrombolysis, within 24 hrs(TIMI flow ≤ 2during CAG )• Coronary stenting 90 patients• Balloon angioplasty in 91 patients• Salvage 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 group

• No difference in the major bleeding• 1yr mortality was 8% vs 12%• Pts with AMI, failed thrombolysis benefit from

rescue mechanical reperfusion in terms of myocardial salvage

• Stenting 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

Thank you