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Trial Vignettes 1-3

Trial Vignettes 1-3. Mark Mason Harefield Hospital Royal Brompton and Harefield NHS Trust. MY CONFLICTS OF INTEREST ARE Research grant from Medtronic. EXPORT AMI. 1ry objective:

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Trial Vignettes 1-3

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  1. Trial Vignettes 1-3 Mark Mason Harefield Hospital Royal Brompton and Harefield NHS Trust

  2. MY CONFLICTS OF INTEREST ARE Research grant from Medtronic

  3. EXPORT AMI • 1ry objective: evaluate flow improvement in pts with AMI within 12 hours of Sx onset undergoing conventional stenting or 1ry aspiration with Export catheter followed by stenting

  4. EXPORT AMI

  5. EXPORT AMI • Primary endpoint: rates of ST resolution >50% (60 minutes post-procedure) and/or Blush grade III; why? • In AMI, TIMI III restored in 94% but normal perfusion in only 28% • Blush 0: no blush • Blush 1: blush but no clearance • Blush 2: blush which clears minimally or not at all in 3 cardiac cycles • Blush 3: blush washes out and clears in 3 cycles

  6. p 1ry endpoint (%) 85 71.9 0.025 No reflow (%) 3.3 10.1 0.04 TIMI frame count 22.82 20.86 0.02 ‘Bailout’ (rescue IIb/IIIa)(%)5.8 14.7 0.02 MACCE @ 30 days(%) 5.8 4.7 0.675 EXPORT AMI

  7. EXPORT AMI • Conclusions • Restoration of TIMI III flow does not necessarily prevent infarction • Use of Export aspiration device appears safe • Routine use of Export device appears associated with improvements in surrogates of microvascular reperfusion (disappointing that there is no attempt to evaluate final infarct size- ?underpowered) • No difference in MACCE at 30 days

  8. HORIZONS AMI • Assessed at 30 days, 6 months and 1-5 years • Primary objectives: • Bivalirudin offers equivalence or reduction in composite of MACE and major bleeding • Bivalirudin offers equivalence or reduction in major bleeding • Includes all-comers inc. LMS and shock

  9. UFH + GP IIb/IIIa Inhibitor N=1802 Bivalirudin Monotherapy N=1800 HORIZONS AMI • 30 day results (stent randomisation still blinded): • F/U available for 1778 UFH arm vs. 1777 Bivalirudin CABG Primary PCI Deferred PCI Medical Rx

  10. HORIZONS AMI Diff = -2.9% [-4.9, -0.8] RR = 0.76 [0.63, 0.92] PNI ≤ 0.0001 Psup = 0.006 Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77] PNI ≤ 0.0001 Psup ≤ 0.0001 Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30] Psup = 1.00 1 endpoint 1 endpoint • *Not related to CABG • **MACE = All cause death, reinfarction, ischemic TVR or stroke

  11. 30 day Stent Thrombosis UFH + GP IIb/IIIa (N=1553) Bivalirudin (N=1571) P Value ARC definite or probable* 1.9% 2.5% 0.33 - definite 1.4% 2.2% 0.11 - probable 0.5% 0.3% 0.26 - acute (≤24 hrs) 0.3% 1.3% 0.0009 - subacute (>24 hrs – 30d) 1.7% 1.2% 0.30 *Protocol definition of stent thrombosis, CEC adjudicated Overall mortality at 30 days 3.1% UFH vs. 2.1% Bivalirudin, p=0.048

  12. HORIZONS AMI • Conclusions • There appears to be a clear treatment difference at 30 days • This appears to be exclusively due to a reduction in bleeding complications • There does appear to be a lower mortality with bivalirudin at 30 days BUT • There is a significantly higher incidence of acute stent thrombosis

  13. AMIHOT II (!) • AMIHOT I • 269 pts with anterior or large inferior MI, TIMI < 2, undergoing primary or rescue PCI within 24 hours of symptoms • I/C supersaturated O2 post-PCI for 90 minutes • No overall difference in infarct size, ST resolution, improvement in regional wall motion BUT • Anterior infarcts reperfused within 6 hours had reduced infarct size, higher incidence of complete ST resolution and more improvement in regional wall motion

  14. AMIHOT II • Anterior MI reperfused by stenting within 6 hours • TIMI < 2 at presentation • Two primary endpoints: • Efficacy- infarct size (superiority) by SPECT sestamibi at 14 days • Safety- 30 day MACE (non-inferiority) ‘Bayesian hierarchical modelling’ allowed for pooling of data from AMIHOT I and II (!)

  15. AMIHOT II • No difference in primary endpoints in AMIHOT II • No difference in proportion with ‘0%’ infarcts • HOWEVER………

  16. AMIHOT II • When AMIHOT I and II pooled: • Infarct size reduced (p=0.023) • Higher proportion of ‘0%’ LV infarcts (18.3% SSO2 vs. 10.3%, p=0.03) • No difference in MACE • 4.7% all pts/3.8% AMIHOT II + ant MI < 6hrs AMIHOT I Vs. 5.9%/5.5% respectively, p= 0.57/0.48

  17. AMIHOT II • Observations: • AMIHOT II was a negative study • Questionable clinical validity of pooling data in this way • Study groups chosen at opposite extremes- • < 6 hours includes pts who would do well anyway • Up to 24 hours will include pts who will not do well regardless • SPECT data might be more useful if ‘acute’ and ‘convalescent’ scan performed • Conclusions: • This evidence does not suggest any clinically useful myocardial salvage

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