The use of intravenous enoxaparin in elective percutaneous coronary intervention in patients with renal impairment: Results from the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial

Received 15 May 2008; accepted 20 August 2008. published online 13 November 2008.

Background

The STEEPLE trial assessed outcomes of patients undergoing elective percutaneous coronary intervention randomized to receive a bolus of intravenous enoxaparin (0.5 or 0.75 mg/kg, n = 2,298) or activated clotting time–adjusted unfractionated heparin (UFH, n = 1,230), stratified according to planned glycoprotein IIb/IIIa inhibitor use.

Methods

In this subanalysis, we assessed outcomes in patients with renal impairment (creatinine clearance ≤60 mL/min, n = 659).

Results

Major bleeding occurred more often in patients with renal impairment compared with those without (2.7% vs 1.5%, P = .04). Enoxaparin was associated with less major bleeding than UFH with normal renal function (0.9% for enoxaparin 0.5 mg/kg or 1.0% for enoxaparin 0.75 mg/kg vs 2.6%, respectively; both P = .01 vs UFH), with a trend toward less major bleeding with impaired renal function (2.6% or 1.8% vs 3.8%, P = .18 for enoxaparin 0.5 mg/kg and P = .47 for 0.75 mg/kg vs UFH). Minor bleeding rates were similar irrespective of renal function or anticoagulation regimen. The incidence of death, nonfatal myocardial infarction, or urgent target-vessel revascularization was similar between patients with and without renal impairment (5.7% vs 6.5%, P = .45). In patients with renal impairment, event rates were 6.2% or 5.3% with enoxaparin vs 5.6% with UFH (P = nonsignificant). Target anticoagulation levels were achieved 4 to 5 times more often with enoxaparin compared with UFH in patients with normal and impaired renal function (both P < .0001).

Conclusions

A single bolus of enoxaparin was associated with similar ischemic events and a trend for less major bleeding compared with UFH in patients with renal impairment undergoing percutaneous coronary intervention. Enoxaparin can be administered safely without dose adjustment in these patients.

a Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand

b Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada

c Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ

d Service de Cardiologie, Hôpital Bichat, Paris, France

e Department of Cardiology, Flinders Medical Center, Adelaide, South Australia, Australia

f Abteilung Innere Medizin III, Universitätsklinikum Freiburg, Freiburg, Germany

g The Adjunct Faculty, Geisinger Clinic, Geisinger Center for Health Research, Danville, PA

h Institut de Cardiologie (AP-HP) and INSERM Unit #856 Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France

Reprint requests: Harvey White, DSc, Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, 1030 Auckland, New Zealand.

Registered trial no. NCT00077844.

The STEEPLE trial was funded by Sanofi Aventis (Paris, France). Dr White reports receiving grant support, consulting fees, and lecture fees from Sanofi Aventis and The Medicines Company (Parsippany, NJ), and grant support from Proctor and Gamble (Cincinnati, OH), Alexion (Cheshire, CT), Schering Plough (Kenilworth, NJ), and Eli Lilly (Indianapolis, IN). Dr Gallo reports having received grant support, consulting fees, and lecture fees from Sanofi Aventis; lecture fees from Abbott Interventional (Chicago, IL), Oryx Pharmaceuticals (Mississauga, Ontario, Canada), and Biovail Pharmaceuticals (Mississauga, Ontario, Canada); and consulting fees from Biovail Pharmaceuticals. Dr Cohen reports receiving grant support from Aventis Pharmaceuticals (Strasbourg, France), consulting fees from Sanofi Aventis and AstraZeneca (London, United Kingdom), and lecture fees from Sanofi Aventis, Merck (Whitehouse Station, NJ), and Schering (Berlin-Wedding, Germany). Dr Steg reports receiving grant support from Sanofi Aventis; consulting fees from Sanofi-Aventis, Takeda (Osaka, Japan), AstraZeneca, Bristol-Myers Squibb (New York, NY), Endotis (Romainville, France), Lilly, Merck Sharpe & Dohme (Whitehouse Station, NJ), GlaxoSmithKline (London, United Kingdom), Pfizer (New York, NY), Servier (Neuilly-sur-Seine, France), The Medicines Company; and speakers bureau from AstraZeneca, Boehringer Ingelheim (Ingelheim, Germany), Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe & Dohme, Novartis (Basel, Switzerland), Nycomed (Zurich, Switzerland), Sanofi Aventis, Sankyo (Tokyo, Japan), Servier, The Medicines Company, and ZLB Behring (West Sussex, United Kingdom). Dr Aylward reports receiving grant support from Sanofi Aventis, Proctor and Gamble, Alexion, The Medicines Company, Schering Plough, and Eli Lilly, as well as consulting fees and lecture fees from Sanofi Aventis and Bristol-Myers Squibb. Dr Bode reports receiving consulting and lecture fees from Sanofi Aventis, Lilly, and GlaxoSmithKline; consulting fees from Nycomed; and lecture fees from AstraZeneca. Dr Steinhubl is currently employed by The Medicines Company; before this appointment, Dr Steinhubl reports receiving consulting fees from Sanofi-Aventis, The Medicines Company, AstraZeneca, Eli Lilly, Cardax Pharmaceuticals (Aiea, HI), and Daiichi Sankyo. Dr Montalescot reports receiving grant support, consulting fees, and lecture fees from Sanofi Aventis, Eli Lilly, and Bristol-Myers Squibb; consulting and lecture fees from Schering-Plough and The Medicines Company; and lecture fees from GlaxoSmithKline.

PII: S0002-8703(08)00734-5

doi:10.1016/j.ahj.2008.08.019

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