Safety and Efficacy of Intravenous Enoxaparin in Safety and Efficacy of Intravenous Enoxaparin in Elective Percutaneous Coronary Intervention: an Elective Percutaneous Coronary Intervention: an International Randomized Evaluation (STEEPLE)International Randomized Evaluation (STEEPLE)

Safety and Efficacy of Intravenous Enoxaparin in Safety and Efficacy of Intravenous Enoxaparin in Elective Percutaneous Coronary Intervention: an Elective Percutaneous Coronary Intervention: an International Randomized Evaluation (STEEPLE)International Randomized Evaluation (STEEPLE)

Presented atPresented atThe European Society of Cardiology The European Society of Cardiology

Hot Line Session 2005Hot Line Session 2005

Presented by Dr. Gilles MontalescotPresented by Dr. Gilles Montalescot

STEEPLE TrialSTEEPLE TrialSTEEPLE TrialSTEEPLE Trial

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IV enoxaparin0.5 mg/kgn=1070

IV enoxaparin0.5 mg/kgn=1070

STEEPLE TrialSTEEPLE TrialSTEEPLE TrialSTEEPLE Trial

Presented at ESC 2005Presented at ESC 2005

IV enoxaparin0.75 mg/kgn=1228

IV enoxaparin0.75 mg/kgn=1228

3528 patients age >18 years undergoing non-emergent single or multi-vessel PCI (performed with a femoral approach)

Randomized25% 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

3528 patients age >18 years undergoing non-emergent single or multi-vessel PCI (performed with a femoral approach)

Randomized25% 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

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; all-cause mortality; myocardial infarction; urgent target vessel revascularization at 30 days

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; all-cause mortality; myocardial infarction; urgent target vessel revascularization at 30 days

Activated clotting time (ACT) – adjusted IV unfractionated heparin (UFH) regimenWith 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

Activated clotting time (ACT) – adjusted IV unfractionated heparin (UFH) regimenWith 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

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STEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hours

6.0%6.6%

8.7%

0%

5%

10%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

6.0%6.6%

8.7%

0%

5%

10%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

Analysis of non-CABG major or minor bleeding (%)

Presented at ESC 2005Presented at ESC 2005

• The primary endpoint of non-CABG major or minor bleeding was lower in those groups treated with enoxaparin

• 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

p=0.014 vs UFHp=0.014 vs UFH

p=0.052 vs UFHp=0.052 vs UFH

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STEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hours

1.2% 1.2%

2.8%

0%

1%

2%

3%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

1.2% 1.2%

2.8%

0%

1%

2%

3%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

Analysis of major bleeding (%)

Presented at ESC 2005Presented at ESC 2005

• 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

p=0.005 vs UFHp=0.005 vs UFH

p=0.007 vs UFHp=0.007 vs UFH

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STEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hoursSTEEPLE Trial: Primary Endpoint at 48 hours

4.9%5.4%

5.9%

0%

2%

4%

6%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

4.9%5.4%

5.9%

0%

2%

4%

6%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

Analysis of minor bleeding (%)

Presented at ESC 2005Presented at ESC 2005

• 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

P=0.315 vs UFHP=0.315 vs UFH

P=0.530 vs UFHP=0.530 vs UFH

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STEEPLE Trial: Secondary EndpointSTEEPLE Trial: Secondary EndpointSTEEPLE Trial: Secondary EndpointSTEEPLE Trial: Secondary Endpoint

Analysis of patients reaching target anticoagulation levels at the start and end of procedure (%)

Presented at ESC 2005Presented at ESC 2005

• 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%

91.7%

19.7%

0%

20%

40%

60%

80%

100%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

78.8%

91.7%

19.7%

0%

20%

40%

60%

80%

100%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

p<0.001 vs UFHp<0.001 vs UFH

p<0.001 vs UFHp<0.001 vs UFH

www. Clinical trial results.org

STEEPLE Trial: Secondary EndpointSTEEPLE Trial: Secondary EndpointSTEEPLE Trial: Secondary EndpointSTEEPLE 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

Presented at ESC 2005Presented at ESC 2005

• 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%)

• There was no difference in death or MI individually

7.2%7.9%

8.4%

0%

5%

10%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

7.2%7.9%

8.4%

0%

5%

10%

Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH

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STEEPLE Trial SummarySTEEPLE Trial SummarySTEEPLE Trial SummarySTEEPLE 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.

• 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.

Presented at ESC 2005Presented at ESC 2005