Safety and Efficacy of Intravenous Enoxaparin in Elective Percutaneous Coronary Intervention: An International Randomised Evaluation One year follow-up G. Montalescot, H.D. White, R. Gallo, M. Cohen, G. Steg, P.E.G. Aylward, C. Bode, M. Chiariello, S.B. King III, R.A. Harrington, W.J. Desmet, C. Macaya, S.R. Steinhubl, on behalf of the STEEPLE investigators.

STEEPLE trial Primary objective To demonstrate the superior safety profile of IV enoxaparin (0.5mg/kg and 0.75mg/kg) compared with IV UFH, up to 48 hours after elective PCI

STEEPLE study design Drug Dose Monitoring i.v. UFH Primary objective: non-CABG bleeding at 48 hours 70–100 IU/kg 50–70 IU/kg ACT i.v. enoxaparin 0.75 mg/kg0.50 mg/kg Stratifiedwith GP IIb/IIIa inhibitor use N = 3,528 PCI ACT = activated clotting time; CABG = coronary artery bypass graft; GP = glycoprotein; UFH = unfractionated heparin. Drug Dose Monitoring No GP IIb/IIIa inhibitor + GP IIb/IIIa inhibitor Drug Dose Monitoring i.v. UFH Primary objective: non-CABG bleeding at 48 hours 70–100 IU/kg 50–70 IU/kg ACT i.v. enoxaparin 0.75 mg/kg0.50 mg/kg Stratifiedwith GP IIb/IIIa inhibitor use N = 3,528 PCI i.v. UFH Primary objective: non-CABG bleeding at 48 hoursPrimary objective: non-CABG bleeding at 48 hours 70–100 IU/kg 50–70 IU/kg ACT i.v. enoxaparin 0.75 mg/kg0.50 mg/kg Stratifiedwith GP IIb/IIIa inhibitor use N = 3,528 PCI ACT = activated clotting time; CABG = coronary artery bypass graft; GP = glycoprotein; UFH = unfractionated heparin.

Non-CABG-related bleeding: primary endpoint Major and Minor BleedingMajor Bleeding Patients (%) P= P= P= P= % Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH Montalescot et al. NEJM 2006; 355:

Individual ischaemic endpoints at 30 days Enoxaparin 0.5 mg/kg Enoxaparin 0.75 mg/kg UFH Non-fatal MI DeathUTVR p = all NS NS = not significant. Montalescot et al. NEJM 2006; 355:

STEEPLE 1-year follow-up The aim of the STEEPLE 1-year follow-up is to evaluate the long-term outcome of patients treated with enoxaparin and UFH Primary analysis: all cause mortality up to 1 year Secondary analyses: –Composite of all-cause mortality up to 1 year and non-CABG major bleeding up to 48h –Composite of all-cause mortality up to 1 year, non- fatal MI/UTVR up to 30 days and non-CABG major bleeding up to 48h –Predictors of 1-year mortality

Statistical analysis All-cause mortality up to 1 year after index PCI calculated using Cox proportional hazard model Univariate and multivariate analyses performed to identify risk factors associated with 1-year all-cause mortality Risk factors investigated included –Ischemic events (MI / UTVR) –Major bleeding –Baseline patient characteristics

Mortality: 1 month to 1 year Enoxaparin 0.5 Enoxaparin 0.75 UFH Days after 1 month p = all NS 1.4% 2.0% 1.5% Endpoint (%)

Mortality: At 1 year Days from randomisation p = all NS 2.3% 2.2% 1.9% Endpoint (%) Enoxaparin 0.5 Enoxaparin 0.75 UFH

Enoxaparin UFH Days from randomisation Endpoint (%) p = % 4.7% Major bleeding (48h) and Mortality (1yr), enoxaparin arms combined (prespecified EP)

Effects of initial ischemic events & major bleeding on 1-year mortality Non-fatal MI/UTVR up to day 30 Major bleeding up to 48h Yes No 1-year mortality rate (%) P= P<0.001

Risk factors for 1-year mortality: Multivariate analysis # Diseased arteries (1> vs. 1) Peripheral arterial disease Age ≥ 75 yr Diabetes Renal insufficiency Low ASA dose during PCI P = P = P = P = P = P = Risk factors P-Value MI/UTVR up to 30 days Major bleeding up to 48h P < P = Hazard ratio (95% CI)

Conclusions 1.STEEPLE showed superior safety of enoxaparin 0.5 mg/kg over UFH in elective PCI 2.1-year mortality rates were low and similar in patients receiving enoxaparin or UFH during elective PCI 3.Incidence of ischemic events up to 30 days after PCI is the strongest independent predictor of 1-year mortality 4.Other independent predictors of 1-year mortality include major bleeding up to 48h post-PCI and high-risk patient characteristics 5.Enoxaparin was associated with significantly lower incidence of early major bleeding and 1-year mortality