Synergy Study Confirms Benefits of Lovenox in Management of High-Risk Non-ST-Elevation ACS Patients

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, [phone],

, or On-site at ACC - [phone]; or Karen Dombek

of MCS Public Relations, 1-800-477-9626, , or On-site at ACC -

[phone]



Web site:  http://www.aventis-us.com/ 

Copyright