Healthcare Industry News: Sanofi-aventis
News Release - September 7, 2006
The New England Journal of Medicine Publishes the STEEPLE Study Which Demonstrated Superior Safety Profile of LOVENOX(R)(Enoxaparin Sodium Injection) Vs. Unfractionated Heparin in Patients Undergoing Non-Emergent Percutaneous Coronary Intervention (PCI)International Study Reveals Benefits of Treatment with Intravenous Enoxaparin, Including Achievement of Target Anticoagulation Levels and the Reduction of Major Bleeding When Compared to IV Unfractionated Heparin (UFH)
BRIDGEWATER, N.J., Sept. 7 (HSMN NewsFeed) -- The New England Journal of Medicine publishes the international STEEPLE trial (Safety and Efficacy of Enoxaparin in Percutaneous Coronary Intervention (PCI): An International Randomized Evaluation), which showed that a single intravenous bolus of enoxaparin of 0.5 mg/kg is associated with significantly less major bleeding, and both studied doses were associated with more predictable anticoagulation levels and similar efficacy than the current standard, unfractionated heparin (UFH), in patients undergoing elective PCI or coronary angioplasty.
PCI is a treatment procedure that unblocks coronary arteries that have narrowed due to atherosclerosis or atherothrombosis, without performing surgery. PCI refers to the broad group of percutaneous techniques that are capable of relieving coronary narrowing and keep the coronary artery open: balloon angioplasty, or implantation of intracoronary stent. Elective PCI is performed in non-emergency cases, when the patient is not in an acute phase of coronary arterial disease (CAD).
STEEPLE was an international, prospective, randomized, open-label, parallel group trial evaluating the safety and efficacy of a single intravenous bolus of enoxaparin 0.5 mg/kg and 0.75 mg/kg versus Activated Clotting Time (ACT)-adjusted intravenous UFH in patients undergoing non-emergency PCI. The study was conducted in 3,528 patients in 124 sites in 9 countries (Australia, Belgium, Canada, Italy, France, Germany, New Zealand, Spain and US). The primary endpoint of the trial was the incidence of major and minor bleeding at 48 hours after the index PCI (excluding bypass graft [CABG] bleeding). The main secondary endpoint was the achievement of therapeutic anticoagulation at the beginning and end of the procedure.
"UFH has been the standard anticoagulant used during PCI procedures, and the STEEPLE trial was the first large scale, randomized, controlled, open-label trial to compare intravenous enoxaparin to UFH during PCI," said Gilles Montalescot, MD, PhD Professor of Cardiology, Hopital la Pitie-Salpetriere Institut du Coeur in Paris, France and Chairman of the Steering Committee for the STEEPLE trial.
In the STEEPLE trial, enoxaparin was associated with reduced bleeding. The incidence of major and minor bleeding (primary endpoint) was 31% lower in the enoxaparin 0.5 mg/kg group (5.9% vs. 8.5%, P=0.01), which was statistically significant for superiority, while the enoxaparin 0.75 mg/kg group was non-inferior to UFH (6.5% vs. 8.5%, P=0.051). Major bleeding was also reduced by 57% in both enoxaparin groups versus UFH.
The study also showed that enoxaparin is associated with a fourfold increase in the rate of patients achieving target anticoagulation levels compared with UFH (79% for enoxaparin 0.5 mg/kg and 92% for enoxaparin 0.75 mg/kg versus 20% for UFH [P<0.001]).
In response to the Data Monitoring Committee (DMC), the low-dose enoxaparin arm (0.5 mg/kg) of the trial was prematurely terminated in November 2004. This was based on an apparent but significant increase in all-cause mortality versus the UFH group. Subsequent evaluations of the causes of mortality suggest no link between the enoxaparin group and ischemic events.
"The STEEPLE trial showed intravenous enoxaparin as an alternative to UFH in the non-emergency PCI setting," said Steven R. Steinhubl, MD, one of the study's lead investigators and Director of Cardiovascular Research and Education, Associate Professor of Medicine, Division of Cardiology, University of Kentucky. "Enoxaparin can be administered as a single IV bolus and requires no routine anticoagulation monitoring."
Lovenox is the most widely used LMWH and has been very extensively studied in acute coronary syndrome in more than 50,000 patients.
The STEEPLE trial was sponsored by Sanofi-aventis.
Important Safety Information
LOVENOX® (enoxaparin sodium injection) cannot be used interchangeably with other low-molecular-weight heparins or unfractionated heparin, as they differ in their manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage.
When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low-molecular-weight heparins or heparinoids are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis.
The risk of these events is increased by the use of postoperative indwelling epidural catheters or by the concomitant use of drugs affecting hemostasis. Patients should be frequently monitored for signs and symptoms of neurological impairment. (See boxed WARNING).
As with other anticoagulants, use with extreme caution in patients with conditions that increase the risk of hemorrhage. Dosage adjustment is recommended in patients with severe renal impairment. Unless otherwise indicated, agents that may affect hemostasis should be discontinued prior to LOVENOX® therapy. Bleeding can occur at any site during LOVENOX® therapy. An unexplained fall in hematocrit or blood pressure should lead to a search for a bleeding site. (See WARNINGS and PRECAUTIONS).
Thrombocytopenia can occur with LOVENOX®. In patients with a history of heparin-induced thrombocytopenia, LOVENOX® should be used with extreme caution. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3, LOVENOX® should be discontinued. Cases of heparin-induced thrombocytopenia have been observed in clinical practice. (See WARNINGS).
The use of LOVENOX® has not been adequately studied for thromboprophylaxis in pregnant women with mechanical prosthetic heart values. (See WARNINGS).
LOVENOX® is contraindicated in patients with hypersensitivity to enoxaparin sodium, heparin, or pork products, and in patients with active major bleeding.
Please see accompanying full prescribing information including boxed WARNING.
Please visit www.lovenox.com for complete prescribing information, including boxed WARNING, and additional important information.
The Sanofi-aventis Group is the world's third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, Sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The Sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY )
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expect," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although Sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by Sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2004. Other than as required by applicable law, Sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
Sanofi-aventis Group subsidiaries in the United States include Sanofi-Synthelabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc.
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