Transcript TRANSFER-AMI - Clinical Trial Results

Trial of Routine ANgioplasty and Stenting after
Fibrinolysis to Enhance Reperfusion in Acute
Myocardial Infarction
The TRANSFER-AMI trial
Warren 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
9803mo01, 1
Trial Sponsors
Canadian Institute of Health Research (CIHR)
Hoffman LaRoche, Canada
Stents provided by Abbott Vascular Canada
Disclosures
Consulting Fees & Speakers Honoraria received by
Hoffman Laroche
9803mo01, 2
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
9803mo01, 3
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.
9803mo01, 4
‘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*
PCI Centre
Cath Lab
Cath / PCI within 6 hrs
regardless of
reperfusion status
Successful Reperfusion
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
9803mo01, 5
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
9803mo01, 6
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
9803mo01, 7
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
9803mo01, 8
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
9803mo01, 9
* Endpoint definitions – Cantor WJ, Am Heart J 2008; 155: 19-25
Baseline Characteristics
Age (years)
Age > 75 (%)
Sex (% female)
Medical History (%)
Prior Angina
Prior MI
Prior PCI
Prior Stroke/TIA *
Hypertension
Hyperlipidemia
Current smoker
Diabetes
Standard
Treatment
(n=508)
Pharmacoinvasive
Strategy
(n=522)
56 (49, 66)
10
20
57 (51, 66)
9
21
11
10
4
1
34
29
42
15
12
11
6
3
33
27
44
15
* p< 0.05
9803mo01, 10
Presenting Characteristics
Standard Pharmacoinvasive
Treatment
Strategy
(n=508)
(n=522)
80 (70, 91)
80 (70, 91)
77 (66, 90)
74 (63, 88)
145 (130, 160) 146 (130, 165)
84 (74, 95)
84 (73, 95)
Weight (kg)
Heart rate (beats/min)
Systolic BP (mm Hg)
Diastolic BP (mm Hg)
Killip Class
I
91
II
7
III
1
Anterior ST-elevation
52
Inferior ST-elevation
47
Symptom Onset to TNK (hrs) 2 (1, 3)
92
7
1
56
44
2 (1, 3)
9803mo01, 11
Procedures
Standard
Treatment
(n=508)
Cardiac Cath performed (%)
82
Time- TNK to Cath (hrs)
27 (4, 69)
PCI performed (%)
62
Stent used (% of PCI cases)
98
Time- TNK to PCI (hrs)
18 (4, 73)
PCI within 6 hrs of TNK (%)
38
PCI within 12 hrs of TNK (%)
47
GP IIb/IIIa inhibitor use (%)
53
Time- TNK to GP IIb/IIIa inhib. (hrs) 11 (4, 63)
IABP use (%)
6
CABG performed (%)
8
Pharmacoinvasive
Strategy
(n=522)
97
3 (2, 4)
84
98
4 (3, 5)
89
97
73
4 (3, 5)
7
6
9803mo01, 12
Selected Medications Used
Standard
Treatment
(n=508)
ASA 1st 6 hrs
97
Clopidogrel 1st 6 hrs *
69
Heparin
57
Enoxaparin
55
Beta Blocker 1st 6 hrs
61
ASA at discharge
85
Clopidogrel at discharge
73
Beta Blocker at discharge
79
ACE Inhibitor at discharge
74
Lipid Lowering at discharge
80
Pharmacoinvasive
Strategy
(n=522)
98
87
57
51
55
85
79
81
73
81
* p< 0.05
9803mo01, 13
Primary Endpoint: 30-Day Death, re-MI,
CHF, Severe Recurrent Ischemia, Shock
% 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
Standard PCI > 24 hrs (n=496)
Invasive < 6 hrs (n=508)
0
5
n=496
n=508
422
468
10
15
20
Days from Randomization
415
466
415
463
414
461
25
30
414
460
412
457
9803mo01, 14
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
P-Value
(n=512)
3.7
0.94
3.3
0.044
0.2
0.019
6.5
0.004
2.9
0.069
4.5
0.11
9803mo01, 15
Safety Endpoints - Bleeding
Standard
Treatment
(n=498)
Intracranial hemorrhage
TIMI scale
Major
Major (non-CABG-related)
GUSTO scale
Moderate
Severe
Severe (non-CABG-related)
Transfusions
Pharmacoinvasive
Strategy
P-Value
(n=512)
1.2
0.2
0.066
4.6
3.2
4.3
2.2
0.88
0.33
2.2
1.4
1.2
5.5
3.5
0.6
0.6
7.1
0.26
0.22
0.34
0.31
9803mo01, 16
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)
9803mo01, 17
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
9803mo01, 18