ASSENT- 4 PCI Trial
The Assessment of the Safety and Efficacy of a New
Treatment Strategy for Acute Myocardial Infarction
(ASSENT-4 PCI) Trial
Presented at
The European Society of Cardiology
Hot Line Session 2005
Presented by Dr. Frans Van de Werf
ASSENT- 4 PCI Trial
1667 patients age > 18 years with ST elevation myocardial infarction (summed ST
deviation > 6 mm); time from symptom onset within 6 hrs; intent to perform primary PCI
Randomized
Mean follow-up: 6 mos (30 days reported to date)
63% of patients received clopidogrel/ticlopidine during PCI
Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group
Full-dose TNK + Primary PCI
Primary PCI
60 IU/kg, maximum 4000 IU
70 IU/kg, no maximum dose
n=829
n=838
GP IIb/IIIa inhibitors allowed only for bail
out use
GP IIb/IIIa inhibitors allowed at physician
discretion


Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days.
Secondary Endpoint: Composite of death, shock, or congestive heart failure at 30
days; shock or CHF at 90 days; single components of the composite endpoint.
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: PCI
Patients undergoing PCI
among two treatment groups (%)
Patients undergoing PCI with stent (%)
p=0.02
p=0.01
100%
87.1%
91.1%
100%
81.3%
80%
80%
60%
60%
85.7%
p=0.97
40%
40%
19.1%
20%
20%
19.7%
0%
0%
With stent
TNK + PCI
PCI alone
TNK + PCI
DES
PCI alone
• PCI was performed at a median of 104 minutes following TNK bolus administration
• Median time from symptom onset to randomization was 140 minutes in the combined
therapy group and 135 minutes in the PCI alone group
• 19% of patients were randomized in the ambulance
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: GP IIb/IIIa Inhibitors
GP IIb/IIIa inhibitor administration prior
to and during PCI (%)
p<0.001
60%
50.5%
40%
p<0.001
20%
9.6%
0.2%
3.0%
0%
GP IIb/IIIa inhibitors GP IIb/IIIa inhibitors
prior to PCI
during PCI
TNK + PCI
PCI alone
www. Clinical trial results.org
•GP IIb/IIIa inhibitors were given
more often prior to PCI in the
PCI alone treatment group
•GP IIb/IIIa inhibitors were given
more often during PCI in the
PCI alone treatment group
ASSENT- 4 PCI Trial: TIMI Flow Grade
TIMI grade 3 flow prior to PCI and TIMI grade
2/3 flow post-PCI (%)
p=0.03
95.3%
100%
80%
97.6%
p<0.001
60%
43.6%
•TIMI grade 2/3 post-PCI was
slightly higher in the PCI alone
group (95.3% vs 97.6%)
40%
20%
•TIMI grade 3 flow prior to PCI
was present more frequently in
the TNK + PCI arm (43.6% vs
15.0%)
15.0%
0%
TFG 3 prior to PCI
TNK + PCI
www. Clinical trial results.org
TFG 2/3 post-PCI
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Abrupt Closure, Re-infarction,
and Repeat TVR
Analysis of in-hospital abrupt closure, reinfarction, and repeat TVR (%)
p<0.001
p=0.01
4.4%
4.1%
4%
• In-hospital abrupt closure
occurred more often in the TNK
+ PCI treatment group (1.9% vs
0.1%)
p<0.001
2%
1.9%
1.9%
1.0%
0.1%
0%
Abrupt
closure
Re-infarction
TNK + PCI
www. Clinical trial results.org
Repeat TVR
• Re-infarction occurred more
often in the TNK + PCI
treatment group (4.1% vs 1.9%)
•Repeat TVR occurred more
often in the TNK + PCR
treatment group (4.4% vs 1.0%)
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Pericarditis, Tamponade,
and Cardiac Rupture
Analysis of in-hospital pericarditis, tamponade,
and cardiac rupture (%)
p=0.11
1.0%
p=0.07
0.9%
p=0.50
0.7%
• Presence of tamponade did
not differ significantly between
the two treatment groups
0.6%
0.5%
• Pericarditis occurred more
often in the TNK + PCI
treatment group (0.7% vs 0.1%)
0.4%
0.2%
0.1%
0.0%
Pericarditis
Tamponade
TNK + PCI
www. Clinical trial results.org
Cardiac
Rupture
•Cardiac rupture occurred more
often in the TNK + PCR
treatment group (0.9% vs 0.2%)
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: EM Dissociation, Pulmonary
Edema, and VF
Analysis of in-hospital EM dissociation,
pulmonary edema, and VF (%)
p=0.08
6.0%
4.0%
2.0%
5.6%
p=0.78
p=0.20
3.4%
3.7%
3.1%
1.7%
1.0%
0.0%
EM
dissociation
Pulmonary
edema
TNK + PCI
www. Clinical trial results.org
VF
• Presence of EM dissociation
did not differ significantly
between the two treatment
groups
• Presence of pulmonary edema
did not differ significantly
between the two treatment
groups
•VF occurred more often in the
TNK + PCR treatment group
(5.6% vs 3.7%)
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Mortality at 30 days
Analysis of mortality at 30 days (%)
p = 0.04
8%
6%
6.0%
3.8%
4%
•The primary endpoint of
mortality was higher in the
TNK + PCI treatment group
compared with the PCI alone
group (6.0% vs 3.8%, p=0.04)
at 30 days
2%
0%
n=50
TNK + PCI
www. Clinical trial results.org
n=32
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Mortality Subgroup Analysis
Subgroup analysis of mortality based on
site of randomization (%)
8%
7.3%
6.0%
6%
4%
4.0%
3.8%
3.1%
3.7%
2%
0%
n=754
Hospitals
with on-site
PCI
n=588
n=325
Community
hospitals
TNK + PCI
www. Clinical trial results.org
Ambulance
•The greatest mortality
difference by treatment group
was seen in hospitals with onsite PCI (7.3% vs 3.8%), with
less difference in community
hospitals (6.0% vs 4.0%), and a
shift in direction for patients
enrolled in the ambulance (3.1%
vs 3.7%)
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Total Stroke and ICH at 30 days
Analysis of total stroke and ICH at 30 days (%)
p<0.001
2.0%
1.81%
p=0.004
1.5%
0.97%
1.0%
•Total stroke occurred more
often in the TNK + PCI group
(1.81% vs 0%), as did ICH
(0.97% vs 0%) at 30 days
0.5%
0
0
0.0%
Total stroke
TNK + PCI
www. Clinical trial results.org
ICH
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Ischemic Stroke, Haemorrhagic
Conversion, and Unclassified Stroke Rates at 30 days
Analysis of ischemic stroke, haemorrhagic conversion,
and unclassified stroke rates at 30 days (%)
1.0%
p=0.03
0.60%
p=0.25
p=0.50
0.5%
0.24%
0.12%
0
0
0
•Ischemic stroke occurred
more often in the TNK +
PCI group (0.60% vs 0%),
as did haemorrhagic
conversion (0.12% vs 0%)
at 30 days
0.0%
Ischemic stroke
Haemorrhagic
conversion
TNK + PCI
www. Clinical trial results.org
Unclassified
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Bleeding Events at 30 days
Analysis of bleeding events at 30 days (%)
p<0.001
31.3%
30%
23.4%
20%
10%
p=0.26
5.7%
4.4%
0%
Major bleed
TNK + PCI
www. Clinical trial results.org
Any bleeding event
• No difference in the frequency
of major bleed existed between
the two treatment groups (5.7%
vs 4.4%) at 30 days
•The presence of any bleeding
event (major + minor bleeding)
was more common in the TNK+
PCI treatment group (31.3% vs
23.4%) at 30 days (p<0.001)
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Transfusions at 30 days
Analysis of transfusions at 30 days (%)
4%
•The percentage of transfusions
administered was greater in the
TNK + PCI treatment group
3.8%
2.7%
2%
2.5%
1.5%
0%
1-2 units
TNK + PCI
www. Clinical trial results.org
•93.8% received no transfusion
in the TNK + PCI treatment
group; 95.8% received no
transfusion in the PCI alone
treatment group (p=0.21)
>2 units
PCI alone
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Previous
ASSENT Trials (TNK in MI patients)
Analysis of 30-day death among other ASSENT trials (%)
8%
6.2%
6.0%
6.0%
6.0%
6%
3.8%
4%
2%
0%
30-day death
ASSENT-2
ASSENT-3
ASSENT 3+
ASSENT-4 TNK + PCI
• Outcomes in the TNK + PCI
treatment group did not differ
from previous ASSENT trials
•Outcomes in the PCI alone
treatment group showed a
significant decrease in
percentage of deaths at 30 days
ASSENT-4 PCI Alone
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Previous
ASSENT Trials (TNK in MI patients)
Analysis of ICH across all ASSENT trials (%)
1.5%
1.0%
• Outcomes in the TNK + PCI
treatment group did not differ
from previous ASSENT trials
0.93% 0.93% 0.97% 0.97%
0.5%
0%
0.0%
ICH
ASSENT-2
ASSENT-3
ASSENT 3+
ASSENT-4 TNK + PCI
•Outcomes in the PCI alone
treatment group showed a
significant decrease in
percentage of ICH cases
ASSENT-4 PCI Alone
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Previous
ASSENT Trials (TNK in MI patients)
Analysis of total stroke across all ASSENT trials (%)
2.0%
1.8% 1.7%
1.8%
• Outcomes in the TNK + PCI
treatment group did not differ
significantly from previous
ASSENT trials
1.5%
1.5%
1.0%
0.5%
0%
0.0%
Total stroke
ASSENT-2
ASSENT-3
ASSENT 3+
ASSENT-4 TNK + PCI
•Outcomes in the PCI alone
treatment group showed a
significant decrease in
percentage of total stroke
ASSENT-4 PCI Alone
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Previous
ASSENT Trials (TNK in MI patients)
Analysis of re-infarction among other ASSENT trials (%)
5.8%
6%
4.1%
5.2%
4.2%
4%
2.7%
2%
0%
Re-infarction
ASSENT-2
ASSENT-3
ASSENT 3+
ASSENT-4 TNK + PCI
• Outcomes in the TNK + PCI
treatment group did not differ
significantly from previous
ASSENT trials
•Outcomes in the PCI alone
treatment group showed a
significant decrease in
percentage of re-infarction
cases
ASSENT-4 PCI Alone
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Previous
ASSENT Trials (TNK in MI patients)
Analysis of major bleed among other ASSENT trials (%)
6%
5.7%
4.7%
4.4%
4%
2.2%
2.8%
2%
0%
Major bleed
ASSENT-2
ASSENT-3
ASSENT 3+
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
www. Clinical trial results.org
• Outcomes in the TNK + PCI
treatment group differed
significantly from the ASSENT-3
and ASSENT 3+ Trials results
•Outcomes in the PCI alone
treatment group did not differ
from the ASSENT-2 Trial, but
were more significant in
comparison to the ASSENT-3
and ASSENT 3+ Trials
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Those in
Primary-PCI Overview
Analysis of 30-day death among ASSENT-4 and those in
the primary-PCI overview (%)
8%
7.0%
6.0%
6%
4%
3.8%
2%
0%
30-day death
• Outcomes in the TNK + PCI
treatment group did not differ
significantly compared with the
primary-PCI overview
•Outcomes in the PCI alone
treatment group were
significantly lower than those in
the primary-PCI overview
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
Primary-PCI overview
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Those in
Primary-PCI Overview
Analysis of ICH among ASSENT-4 and those in the
primary-PCI overview (%)
1.0%
0.97%
• Outcomes in the TNK + PCI
treatment group were
significantly higher compared
with the primary-PCI overview
0.5%
0%
0.05%
0.0%
ICH
•Outcomes in the PCI alone
treatment group did not differ
from the primary-PCI overview
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
Primary-PCI overview
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Those in
Primary-PCI Overview
Analysis of total stroke among ASSENT-4 and those in
the primary-PCI overview (%)
2%
1.8%
1.1%
1%
0%
0%
Total stroke
• Outcomes in the TNK + PCI
treatment group were higher
compared with the primary-PCI
overview
•Outcomes in the PCI alone
treatment group were
significantly lower compared
with the primary-PCI overview
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
Primary-PCI overview
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Those in
Primary-PCI Overview
Analysis of re-infarction among ASSENT-4 and those in
the primary-PCI overview (%)
8%
6%
4%
5.2%
2.7%
2.5%
2%
0%
Re-infarction
• Outcomes in the TNK + PCI
treatment group were higher
compared with the primary-PCI
overview
•Outcomes in the PCI alone
treatment group did not differ
with the primary-PCI overview
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
Primary-PCI overview
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Comparison with Those in
Primary-PCI Overview
Analysis of major bleed among ASSENT-4 and those in
the primary-PCI overview (%)
8%
6%
7.0%
5.7%
4.4%
4%
2%
0%
Major bleed
• Outcomes in the TNK + PCI
treatment group were lower
compared with the primary-PCI
overview
•Outcomes in the PCI alone
treatment group were
significantly lower compared
with the primary-PCI overview
ASSENT-4 TNK + PCI
ASSENT-4 PCI Alone
Primary-PCI overview
www. Clinical trial results.org
Presented at ESC 2005
ASSENT- 4 PCI Trial: Summary
• The trial intended to enroll 4,000 patients, but was discontinued
early after enrollment of 1,667 patients.
• Among patients with ST elevation MI intended for primary PCI,
administration of full-dose fibrinolytic (TNK) immediately prior to
PCI was associated with increased mortality and stroke at 30
days compared with primary PCI alone.
• Primary endpoint data are not yet available.
• Further evaluation of the clinical benefit of fibrinolytics among
patients undergoing early PCI for STEMI appears warranted
(FINESSE).
www. Clinical trial results.org
Presented at ESC 2005