Upload
howard-fleming
View
227
Download
0
Embed Size (px)
DESCRIPTION
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
Citation preview
Trial Vignettes 1-3
Mark MasonHarefield Hospital
Royal Brompton and Harefield NHS Trust
MY CONFLICTSOF INTEREST ARE
Research grant from Medtronic
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
EXPORT AMI
Primary aspiration (n=120) Conventional stenting (n=129)
AMI within 12 hrs
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
EXPORT AMI
Primary aspiration (n=120) Conventional stenting (n=129)
AMI within 12 hrs
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
p
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
HORIZONS AMI
3000 pts
1 : 3
UFH + IIb/IIIa(n=1802)
Bivalirudin +/- provisional IIb/IIIa(n=1800)
BMS Taxus
PCI CABG Medical Rx
Angio
>3400 pts with STEMI and Sx onset <12 hrs
•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
HORIZONS AMI
• 30 day results (stent randomisation still blinded):
• F/U available for 1778 UFH arm vs. 1777 Bivalirudin
UFH + GP IIb/IIIa InhibitorN=1802
Bivalirudin Monotherapy
N=1800Primary PCI Deferred PCI CABG Medical Rx
HORIZONS AMI
Diff = Diff = 0.0% [-1.6, 1.5] RR = 0.99RR = 0.99 [0.76, 1.30]
PPsupsup = 1.00 = 1.00
Diff = Diff = -3.3% [-5.0, -1.6] RR = RR = 0.60 [0.46, 0.77]
PPNINI ≤ 0.0001 ≤ 0.0001PPsupsup ≤ 0.0001 ≤ 0.0001
Diff = Diff = -2.9% [-4.9, -0.8]RR = RR = 0.76 [0.63, 0.92]
PPNINI ≤ 0.0001 ≤ 0.0001PPsupsup = 0.006 = 0.006
1 endpoint 1 endpoint
*Not related to CABG*Not related to CABG**MACE = All cause death, reinfarction, ischemic TVR or stroke**MACE = All cause death, reinfarction, ischemic TVR or stroke
Overall mortality at 30 days 3.1% UFH vs. 2.1% Bivalirudin, p=0.048
30 day Stent Thrombosis30 day Stent ThrombosisUFH + UFH +
GP IIb/IIIaGP IIb/IIIa(N=1553)(N=1553)
BivalirudinBivalirudin(N=1571)(N=1571)
PPValueValue
ARC definite or probable* 1.9%1.9% 2.5%2.5% 0.330.33
- definite 1.4%1.4% 2.2%2.2% 0.110.11
- probable 0.5%0.5% 0.3%0.3% 0.260.26
- acute (≤24 hrs) 0.3%0.3% 1.3%1.3% 0.00090.0009
- subacute (>24 hrs – 30d) 1.7%1.7% 1.2%1.2% 0.300.30
*Protocol definition of stent thrombosis, CEC adjudicated*Protocol definition of stent thrombosis, CEC adjudicated
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 daysBUT– There is a significantly higher incidence of acute
stent thrombosis
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
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 (!)
AMIHOT II
2.8:1 randomisation
SSO2222
(SPECT 209)
Control79
(SPECT 72)
304 pts enrolled(3 randomisation errors)
301 by ITT
•No difference in primary endpoints in AMIHOT II•No difference in proportion with ‘0%’ infarcts
HOWEVER………
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 IVs.
5.9%/5.5% respectively, p= 0.57/0.48
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