STEEPLE Trial
Safety and Efficacy of Intravenous Enoxaparin in
Elective Percutaneous Coronary Intervention: an
International Randomized Evaluation (STEEPLE)
Presented at
The European Society of Cardiology
Hot Line Session 2005
Presented by Dr. Gilles Montalescot
STEEPLE Trial
3528 patients age >18 years undergoing non-emergent single or multi-vessel
PCI (performed with a femoral approach)
Randomized
25% female, mean age 64 years, mean follow-up 30 days
GP IIb/IIIa inhibitors were used in 41% of patients, and aspirin in 85%
Drug-eluting stents were used in 57% of patients and multivessel PCI was performed in 16% of patients
IV enoxaparin
IV enoxaparin
0.5 mg/kg
0.75 mg/kg
n=1070
n=1228
Activated clotting time (ACT) – adjusted
IV unfractionated heparin (UFH) regimen
With GP IIb/IIIa (50-70 IU dose): target ACT 200-300
Without GP IIb/IIIa (70-100 IU dose): target ACT 300-350
n=1230


Primary Endpoint: Non-CABG related major and minor bleeding by 48 hrs post-PCI
Secondary Endpoint: Percent of patients reaching target anticoagulation levels at the
start and end of the procedure; composite of non-CABG major bleed through 48 hrs; allcause mortality; myocardial infarction; urgent target vessel revascularization at 30 days
www. Clinical trial results.org
Presented at ESC 2005
STEEPLE Trial: Primary Endpoint at 48 hours
Analysis of non-CABG major or minor bleeding (%)
10%
p=0.014
vs UFH
6.0%
p=0.052
vs UFH
• The primary endpoint of
non-CABG major or minor
bleeding was lower in
those groups treated with
enoxaparin
8.7%
6.6%
5%
0%
Enoxaparin 0.5 mg/kg
Enoxaparin 0.75 mg/kg
www. Clinical trial results.org
UFH
• The lower bleeding rate
associated with enoxaparin
was observed both in the
subgroup of patients
intended to be treated with
GP IIb/IIIa inhibitors, as
well as in a per protocol
analysis
Presented at ESC 2005
STEEPLE Trial: Primary Endpoint at 48 hours
Analysis of major bleeding (%)
2.8%
3%
2%
p=0.005
vs UFH
1.2%
p=0.007
vs UFH
1.2%
1%
• Major bleeding occurred in 1.2%
of each of the enoxaparin groups
and 2.8% in the UFH group
• The primary endpoint of major
bleeding was 57% lower in the
enoxaparin groups compared with
the UFH group
0%
Enoxaparin 0.5 mg/kg
Enoxaparin 0.75 mg/kg
www. Clinical trial results.org
UFH
Presented at ESC 2005
STEEPLE Trial: Primary Endpoint at 48 hours
Analysis of minor bleeding (%)
6%
P=0.315
vs UFH
P=0.530
vs UFH
5.4%
5.9%
4.9%
• Minor bleeding occurred in
4.9% (0.5 mg/kg) and 5.4%
(0.75 mg/kg) in each of the
two enoxaparin groups and
5.9% in the UFH group
4%
2%
0%
Enoxaparin 0.5 mg/kg
Enoxaparin 0.75 mg/kg
www. Clinical trial results.org
UFH
Presented at ESC 2005
STEEPLE Trial: Secondary Endpoint
Analysis of patients reaching target anticoagulation levels at the
start and end of procedure (%)
100%
80%
p<0.001
vs UFH
p<0.001
vs UFH
91.7%
• The percent of patients reaching
target anticoagulation levels at
the start and end of the
procedure was significantly
lower among the UFH treatment
group compared with the two
enoxaparin treatment groups
(78.8%, 91.7% vs 19.7%)
78.8%
60%
40%
19.7%
20%
0%
Enoxaparin 0.5 mg/kg
Enoxaparin 0.75 mg/kg
www. Clinical trial results.org
UFH
Presented at ESC 2005
STEEPLE Trial: Secondary Endpoint
Composite endpoint of non-CABG major bleed through 48 hours, all-cause
mortality, MI, or urgent target vessel revascularization at 30 days (%)
p=NS
10%
7.2%
7.9%
• The composite secondary
endpoint was numerically lower
among the two enoxaparin
treatment groups compared with
the UFH treatment group (7.2%,
7.9% vs 8.4%)
8.4%
5%
• There was no difference in death
or MI individually
0%
Enoxaparin 0.5 mg/kg
Enoxaparin 0.75 mg/kg
www. Clinical trial results.org
UFH
Presented at ESC 2005
STEEPLE Trial Summary
• Among patients undergoing non-emergent PCI, treatment with reduced dose
enoxaparin was associated with lower rates of major or minor bleeding by 48
hours post-PCI compared with treatment with ACT-driven UFH.
• Patient enrollment in the enoxaparin 0.5 mg/kg treatment group was
discontinued by the data safety monitoring committee near the end of the trial
at the objection of the steering committee, due to a difference in mortality
between the three groups (p=0.02).
• With full 30 day data, neither mortality, MI, nor urgent target vessel
revascularization differed between the three groups.
• Further investigation is still necessary, but the results from this trial show that
the use of enoxaparin at lower doses in the catheterization laboratory may offer
a potential safety advantage with lower bleeding events relative to ACT guided
UFH.
www. Clinical trial results.org
Presented at ESC 2005