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Trial Sponsors

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  1. Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial InfarctionThe TRANSFER-AMI trialWarren J. Cantor, David Fitchett, Bjug Borgundvaag, Michael Heffernan, Eric A. Cohen, Laurie J. Morrison, John Ducas, Anatoly Langer, Shamir Mehta, Charles Lazzam, Brian Schwartz, Vladimir Dzavik, Amparo Casanova, Paramjit Singh, Shaun G. Goodman on behalf of the TRANSFER-AMI Investigators

  2. Trial Sponsors • Canadian Institute of Health Research (CIHR) • Hoffman LaRoche, Canada • Stents provided by Abbott Vascular Canada • Consulting Fees & Speakers Honoraria received by Hoffman Laroche Disclosures

  3. Background • Treatment delays can reduce or eliminate benefits of primary PCI • STEMI pts presenting to non-PCI centres often cannot undergo primary PCI in timely manner, and therefore receive thrombolysis • The role and optimal timing of routine early PCI after fibrinolysis remains controversial

  4. Objective To compare: Pharmacoinvasive strategy (transfer to PCI centre for routine early PCI within 6 hrs) with Standard treatment (early transfer only for failed reperfusion, otherwise cath > 24 hrs) for high-risk STEMI patients receiving thromboysis at non-PCI centres.

  5. ‘High Risk’ ST Elevation MI within 12 hours of symptom onset Community Hospital Emergency Department TNK + ASA + Heparin / Enoxaparin + Clopidogrel “Pharmacoinvasive Strategy” Urgent Transfer to PCI Centre “Standard Treatment” Assess chest pain, STresolution at 60-90 minutes after randomization Failed Reperfusion* Successful Reperfusion PCI Centre Cath Lab Cath / PCI within 6 hrs regardless of reperfusion status Cath and Rescue PCI  GP IIb/IIIa Inhibitor Elective Cath  PCI > 24 hrs later Repatriation of stable patients within 24 hrs of PCI * ST segment resolution < 50% & persistent chest pain, or hemodynamic instability Randomization stratified by age (≤75 vs. > 75) and by enrolling site

  6. Inclusion Criteria • 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

  7. 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

  8. PCI for Pharmacoinvasive Group • PCI of culprit lesion at time of cath if ≥ 70% stenosis or 50-70% stenosis with high-risk features (thrombus, ulceration, spont dissection) regardless of coronary flow • Stents used whenever technically possible, use of Abbott vascular stents (ML Vision, Mini Vision) encouraged • GP IIb/IIIa inhibitors left to operator’s discretion

  9. Endpoints • 1o Efficacy Endpoint: 30-day composite of Death, Reinfarction, Recurrent Ischemia, CHF, shock * • 2o Efficacy Endponts: Death / Reinfarction at 6 months and 1 Year • Safety Endpoints: Bleeding (GUSTO Severe, TIMI Major) • Endpoints adjudicated by clinical events committee blinded to treatment group * Endpoint definitions – Cantor WJ, Am Heart J 2008; 155: 19-25

  10. PRELIMINARY Baseline Characteristics Pharmacoinvasive Strategy (n=522) 57 (51, 66) 9 21 12 11 6 3 33 27 44 15 Standard Treatment (n=508) 56 (49, 66) 10 20 11 10 4 1 34 29 42 15 Age (years) Age > 75 (%) Sex (% female) Medical History (%) Prior Angina Prior MI Prior PCI Prior Stroke/TIA * Hypertension Hyperlipidemia Current smoker Diabetes * p< 0.05

  11. PRELIMINARY Presenting Characteristics Standard Treatment (n=508) 80 (70, 91) 77 (66, 90) 145 (130, 160) 84 (74, 95) 91 7 1 52 47 2 (1, 3) Pharmacoinvasive Strategy (n=522) 80 (70, 91) 74 (63, 88) 146 (130, 165) 84 (73, 95) 92 7 1 56 44 2 (1, 3) Weight (kg) Heart rate (beats/min) Systolic BP (mm Hg) Diastolic BP (mm Hg) Killip Class I II III Anterior ST-elevation Inferior ST-elevation Symptom Onset to TNK (hrs)

  12. PRELIMINARY Procedures 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 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 (%)

  13. PRELIMINARY Selected Medications Used Standard Treatment (n=508) 97 69 57 55 61 85 73 79 74 80 Pharmacoinvasive Strategy (n=522) 98 87 57 51 55 85 79 81 73 81 ASA 1st 6 hrs Clopidogrel 1st 6 hrs * Heparin Enoxaparin Beta Blocker 1st 6 hrs ASA at discharge Clopidogrel at discharge Beta Blocker at discharge ACE Inhibitor at discharge Lipid Lowering at discharge * p< 0.05

  14. Standard (n=496) Pharmacoinvasive (n=508) Primary Endpoint: 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia, Shock PRELIMINARY % of Patients 18 16.6 16 14 OR=0.537 (0.368, 0.783); p=0.0013 12 10.6 10 8 6 4 2 0 0 5 10 15 20 25 30 Days from Randomization n=496 n=508 422 468 415 466 415 463 414 461 414 460 412 457

  15. PRELIMINARY Components of Primary Endpoint 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 Standard Treatment (n=498) 3.6 6.0 2.2 11.7 5.2 2.6 Death Reinfarction Recurrent Ischemia Death/MI/Ischemia New / worsening CHF Cardiogenic Shock

  16. PRELIMINARY Safety Endpoints - Bleeding Pharmacoinvasive Strategy (n=512) 0.2 4.3 2.2 3.5 0.6 0.6 7.1 P-Value 0.066 0.88 0.33 0.26 0.22 0.34 0.31 Standard Treatment (n=498) 1.2 4.6 3.2 2.2 1.4 1.2 5.5 Intracranial hemorrhage TIMI scale Major Major (non-CABG-related) GUSTO scale Moderate Severe Severe (non-CABG-related) Transfusions

  17. 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 • Benefit seen despite high cath/PCI rates in Standard Treatment group (including ~40% rescue PCI)

  18. 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 • Regional systems should be developed to ensure timely transfers of STEMI patients to PCI centres

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