Synergy Study Confirms Benefits of Lovenox in Management of High-Risk Non-ST-Elevation ACS Patients Findings of UA/NSTEMI Trial Presented at ACC NEW ORLEANS, March 9 /PRNewswire-FirstCall/ -- The results of a landmark, 10,027-patient study show thatLovenox(R) (enoxaparin sodium injection) is as effective as unfractionated heparin (UFH) in the treatment of high-risk patients with non-ST-elevation acute coronary syndromes (ACS) undergoing a rapid invasive strategy. Findings of the SYNERGY trial were presented today during a Late-Breaking Clinical Trials session at the American College of Cardiology's Annual Scientific Session 2004. (Logo: http://www.newscom.com/cgi-bin/prnh/20000501/NYM197 ) "The results of previous trials provide strong evidence of the superiority of enoxaparin over unfractionated heparin in medically managed ACS patients," said Robert Califf, MD, Associate Vice Chancellor for Clinical Research, Director, Duke Clinical Research Institute at Duke University Medical Center, Durham, NC, and a lead investigator of the trial. "Now, data from SYNERGY demonstrate benefit with enoxaparin in aggressive management of this high-risk population as well. Physicians should not hesitate to transition patients to percutaneous coronary intervention while on enoxaparin." In this patient population, Lovenox was established to be at least as effective as UFH in the reduction in the incidence of death or myocardial infarction at 30 days, the primary endpoint (14.0 percent vs. 14.5 percent, p= NS). Safety in SYNERGY was assessed by GUSTO and TIMI major bleeding criteria, rate of transfusions, intracranial hemorrhage (ICH) and bleeding causing hemodynamic instability. Results showed that the incidence of GUSTO severe bleeding was 2.9% with Lovenox(R) vs. 2.4% for UFH (p=NS). Incidence of TIMI non-CABG major bleeding was 2.4% vs. 1.7% (p= 0.025), a statistically significant difference. Incidence of bleeding was confounded by extensive anticoagulant switching. Importantly, there was no difference observed in the incidence of blood transfusions, ICH and abrupt closure. Patients Started and Continued on Lovenox(R) Had Better Outcomes A secondary analysis of 5,637 patients enrolled in SYNERGY showed that those who began treatment with Lovenox(R) prior to randomization and continued on it throughout the course of therapy experienced an 18 percent relative risk reduction in the incidence of death and myocardial infarction at 30 days vs. patients who were started and continued on UFH (12.8% vs. 15.6%, p=0.0029). "Based on these outcomes, enoxaparin would appear to be a preferred first-line therapy. These findings suggest that switching anticoagulant agents during an episode of ACS, including in the cath lab, provides no clinical benefit and increases bleeding complications," said James J. Ferguson, MD, Associate Director of Cardiology Research at the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, TX, and a lead investigator of the study. A meta-analysis of all ACS trials comparing Lovenox to UFH, in a broad spectrum of patients ranging from conservatively to invasively managed, shows that Lovenox significantly reduces the incidence of death and MI, with no significant increase in bleeding complications. SYNERGY Trial Design The SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization & GlYcoprotein IIb/IIIa Inhibitors) trial was a prospective, randomized, open-label study evaluating the efficacy and safety of Lovenox(R) versus UFH in high-risk patients presenting with non-ST-elevation ACS and treated with an early invasive strategy. SYNERGY was conducted at approximately 400 investigative sites in the United States, Canada, Europe and South America. It is the largest trial ever conducted in unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI). All patients enrolled in the study received treatment with Lovenox(R) or UFH and concomitant therapy with oral and intravenous antiplatelet agents. "These findings show that patients receiving enoxaparin throughout the course of therapy experienced significantly better outcomes compared to UFH," said Dr. Califf. "Given the wealth of prior data showing its benefits in the management of ACS patients, its newly demonstrated favorable profile in early invasive patient management, and convenience of use, enoxaparin can be considered an anticoagulant of choice in ACS." About Acute Coronary Syndromes Acute coronary syndromes involve the formation of blood clots in thevessels that supply blood to the heart, resulting in the reduction of blood flow to the heart. These conditions include unstable angina, non-Q-wave or non-ST-elevation myocardial infarctions, and acute myocardial infarction (AMI), or heart attack. According to the American Heart Association, more than 12 million Americans alive today have a history of coronary heart disease (myocardial infarction, angina pectoris or both). Acute coronary syndromes are commonly treated with a combination of anticoagulant medications. Very often, percutaneous coronary intervention (PCI), such as angioplasty, may be necessary in these patients. While UFH traditionally has been used to reduce the risk of blood clots, studies such as the ESSENCE trial have demonstrated the superiority of Lovenox(R) to unfractionated heparin in managing UA/NSTEMI. Low-molecular-weight heparins prevent the formation of a blood clot by inhibiting thrombin, an enzyme present throughout the circulation system. Antiplatelet drugs are effective in preventing blood clotting by inhibiting the aggregation of platelets. PCI describes a procedure used to dilate narrowed arteries to facilitate blood flow in which a balloon catheter with or without a stent is introduced into the blocked artery and inflated to widen its diameter, allowing more blood to flow through. About Lovenox(R) The No. 1-selling low-molecular-weight heparin in the world, Lovenox(R) was approved in the United States and Canada in 1993. It has been available in Europe since 1987 and is known under the brand names Lovenox(R), Clexane(R) and Klexane(R). Lovenox(R) is the only low-molecular-weight heparin approved by the FDA for all of the following indications: * Prophylaxis of deep-vein thrombosis, which may lead to pulmonary embolism: -- for medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness; -- for patients undergoing abdominal surgery who are at risk for thromboembolic complications; -- for patients undergoing hip replacement surgery, during and following hospitalization; -- for patients undergoing knee replacement surgery. * Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. * Inpatient treatment of acute deep-vein thrombosis with or without pulmonary embolism, when administered in conjunction with warfarin sodium. * Outpatient treatment of acute deep-vein thrombosis without pulmonary embolism when administered in conjunction with warfarin sodium. IMPORTANT SAFETY INFORMATION LOVENOX(R) (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(R) therapy. Bleeding can occur at any site during LOVENOX(R) 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(R). In patients with a history of heparin-induced thrombocytopenia, LOVENOX(R) should be used with extreme caution. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3, LOVENOX(R) 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 valves (See WARNINGS.) LOVENOX(R) is contraindicated in patients with hypersensitivity to enoxaparin sodium, heparin, or pork products, and in patients with active major bleeding. Please see accompanying information or go to http://www.lovenox.com/ for complete prescribing information, including boxed WARNING, and additional important information. About Aventis Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. In 2003, Aventis generated sales of euro 16.79 billion (US $18.99), invested euro 2.86 billion (US $3.24) in research and development and employed approximately 69,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. The company's prescription drugs business is conducted in the U.S. by Aventis Pharmaceuticals Inc., which is headquartered in Bridgewater, New Jersey. For more information, please visit: http://www.aventis-us.com/. Statements in this news release containing projections or estimates of revenues, income, earnings per share, capital expenditures, capital structure, or other financial items; plans and objectives relating to future operations, products, or services; future economic performance; or assumptions underlying or relating to any such statements, are forward-looking statements subject to risks and uncertainties. Actual results could differ materially depending on factors such as the timing and effects of regulatory actions, the results of clinical trials, the company's relative success developing and gaining market acceptance for new products, the outcome of significant litigation, and the effectiveness of patent protection. Additional information regarding risks and uncertainties is set forth in the current Annual Report on Form 20-F of Aventis on file with the Securities and Exchange Commission and in the current Annual Report -- "Document de Reference" -- on file with the "Autorite des marches financiers" in France. Pursuant to Article 7 of the COB Regulation no. 2002-04, this press release was transmitted to the Autorite des marches financiers before its release. http://www.newscom.com/cgi-bin/prnh/20000501/NYM197DATASOURCE: Aventis Pharmaceuticals CONTACT: Terri Pedone of Aventis Pharmaceuticals, +1-908-243-6578, , or On-site at ACC - +1-908-797-4499; or Karen Dombek of MCS Public Relations, 1-800-477-9626, , or On-site at ACC - +1-908-244-6411 Web site: http://www.aventis-us.com/

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