New Study Shows that Extending Prophylaxis with Clexane(R) / Lovenox(R) (Enoxaparin Sodium Injection) to 5 Weeks is more Effective than 10 Days for Reducing the Risk of Venous Thromboembolism (VTE) in Acutely Ill Medical Patients with Reduced Mobility

New Study Shows that Extending Prophylaxis with Clexane(R) / Lovenox(R) (Enoxaparin Sodium Injection) to 5 Weeks is more Effective than 10 Days for Reducing the Risk of Venous Thromboembolism (VTE) in Acutely Ill Medical Patients with Reduced Mobility

July 10, 2007

    - EXCLAIM is the First International Study to Show that
Extended
      Thromboprophylaxis Reduces VTE Risk in Acutely-Ill
Medical Patients
      with a Statistically Significant 44%

    PARIS, July 9 /Xinhua-PRNewswire/ -- 

    Sanofi-aventis announced today the results of the
EXCLAIM (Extended Clinical prophylaxis in Acutely Ill
Medical patients) study, which showed the benefit of
extended prophylaxis in acutely ill medical patients with
reduced mobility by demonstrating the superiority of 5
weeks course of prophylaxis with Clexane(R)/Lovenox(R)
compared to 10 days regimen with a statistically
significant 44% reduction in venous thromboembolism (VTE)
events (Deep Vein Thrombosis and / or Pulmonary Embolism).
The findings were presented at the XXIst ISTH Congress
(International Society on Thrombosis and Haemostasis) in
Geneva, Switzerland.

    Acutely ill medical patients are at high risk of VTE.
The benefit of thromboprophylaxis with enoxaparin (10 plus
or minus 4 days) has already been demonstrated in this
patient population and is considered as the standard
regimen(1). Nonetheless clinical practice suggests that the
risk of VTE may continue beyond 10 days(1) particularly in
patients with reduced mobility. The efficacy and safety of
extended prophylaxis in this medical population had never
been assessed although it has been demonstrated for several
high-risk surgical patient populations(2,3) and therefore
recommended by international guidelines(4).

    The objective of EXCLAIM study was to assess the
superiority of enoxaparin prophylaxis given for 28 plus or
minus 4 days versus placebo, both following an initial
treatment with enoxaparin for 10 plus or minus 4 days, to
reduce VTE events rate. The primary efficacy endpoint was
the incidence of asymptomatic deep-vein thrombosis (DVT),
symptomatic DVT, symptomatic pulmonary embolism (PE), or
fatal PE during the double-blind period.

    The statistically significant 44% relative risk
reduction in VTE events observed for extended-duration
prophylaxis with enoxaparin vs. placebo for the primary
endpoint (2.8% vs. 4.9%; p=0.0011) was associated with a
reduction in symptomatic VTE by 73% (0.3% vs. 1.1%;
p=0.0044) and asymptomatic proximal DVT by 34% (2.5% vs.
3.7%; p=0.0319). No statistically significant differences
were observed for symptomatic pulmonary embolism (PE) or
fatal PE. The statistically significant relative risk
reduction of VTE observed with enoxaparin at 38 days was
maintained at 90 days (3.0% vs. 5.2%; p=0.0015).

    Victor F. Tapson, MD, Professor of Medicine, Director,
Center for Pulmonary Vascular Disease, Division of
Pulmonary and Critical Care, Duke University Medical
Center, Durham, NC, and a lead investigator of the EXCLAIM
study said: "What the trial results showed is that
patients do not leave their risk for VTE at the door when
they leave the hospital. With continued prophylaxis,
Lovenox(R) statistically significantly reduced the risk by
44% in acutely ill medical patients with prolonged
immobility."

    In comparison with placebo, the rate of major bleeding
was statistically significantly higher in the extended
enoxaparin arm (0.6% vs. 0.15%, p=0.019), but the overall
event rate was low. There was no difference in all-cause
mortality between extended enoxaparin vs. placebo at 6
months (10.1% vs. 8.9%; p=0.18).

    "EXCLAIM is the first study to assess the benefit
of extended thromboprophylaxis in acutely ill medical
patients with reduced mobility and to demonstrate the
clinical benefit of 5 weeks enoxaparin treatment versus 10
days in this patient population" said Professor
Russell Hull from the University of Calgary, Canada and
Chair of the Steering Committee for the EXCLAIM study.

    "Similarly to the initial demonstration of the
benefit of thromboprophylaxis for acutely ill medical
patients, first established by the MEDENOX trial, the
EXCLAIM study should be a landmark trial in advancing the
standard of care of patients at high risk for VTE and it
further establishes enoxaparin as a reference treatment for
VTE prophylaxis in acutely ill medical patients".

    About EXCLAIM

    The EXCLAIM trial is the first international,
multicenter, prospective, randomized, double-blind,
placebo-controlled study. It enrolled 5,105 acutely-ill
patients with recent reduced mobility in 20 countries,
comparing extended-duration (28 plus or minus 4 days)
venous thromboembolism (VTE) prophylaxis with enoxaparin, a
low-molecular-weight heparin (LMWH) with the standard
regimen of enoxaparin (10 plus or minus 4 days) for the
prophylaxis of VTE.

    Patients recently immobilized for up to 3 days with
level 1 mobility (total bed rest or sedentary patients) or
with level 2 mobility (with bathroom privileges) with age
> 75 years or history of VTE or diagnosis of cancer and
predefined acute medical illness were randomized to
received enoxaparin 40 mg subcutaneously once daily for 10
plus or minus 4 days and were then randomized to receive
the same enoxaparin regimen or placebo for an additional 28
plus or minus 4 days.

    The steering committee followed the Data Safety
Monitoring Board (DSMB) suggestion that in addition to
level 1 mobility patients to re-define the inclusion
criteria by adding on level 2 mobility patients inclusion
criteria: Age >75 years, or prior VTE or diagnosed
cancer.

    The objective of the Exclaim study was to assess the
superiority of enoxaparin prophylaxis given for 28 plus or
minus 4 days versus placebo, both following an initial
treatment with enoxaparin for 10 plus or minus 4 days, to
reduce VTE events.

    The primary efficacy endpoint was the incidence of
asymptomatic deep-vein thrombosis (DVT) detected by routine
standardized ultrasonography, symptomatic DVT, symptomatic
pulmonary embolism (PE), or fatal PE during the
double-blind period. Secondary efficacy endpoints include
the incidence of VTE at 3 months and the incidence of
mortality up to 6 months after enrolment.

    The primary safety endpoint was major hemorrhagic
complications during the same period.

    About venous thromboembolism (VTE)

    Venous thromboembolism is a general term used to
describe the formation of a blood clot (thrombus) that
blocks a vein. This may occur in any part of the venous
system, but the most common manifestations are deep-vein
thrombosis (DVT), usually in the leg, and pulmonary
embolism (PE).

    VTE is also a common complication among acutely-ill
medical patients who have recently been immobilized, a
population of medically-ill patients at particularly
high-risk for VTE.

    About Clexane(R) / Lovenox(R) (enoxaparin)

    Lovenox(R) is a unique chemical entity in a class of
antithrombotic agents known as low-molecular weight heparin
(LMWH). The no. 1 selling low-molecular weight heparin in
the world, Lovenox(R) is obtained by alkaline degradation
of heparin benzyl ester and is about one-third the
molecular size of unfractionated heparin. Lovenox(R) is the
most widely studied LMWH, with 20 years of use in the
treatment of 185 million patients in 96 countries.

    Its clinical applications are linked to its
antithrombotic properties. It is used to inhibit clot
formation in venous and arterial vessels to prevent
potential acute or chronic complications of venous or
arterial thrombosis. As with all anticoagulants, the most
frequently reported side effect with Lovenox(R) is
bleeding. Clinical indications for Lovenox(R) may vary from
one country to another.

    About sanofi-aventis

    Sanofi-aventis is one of the world's leading
pharmaceutical companies, ranking number one in Europe.
Backed by a world-class R&D organisation,
sanofi-aventis is developing leading positions in seven
major therapeutic areas: cardiovascular, thrombosis,
oncology, metabolic diseases, central nervous system,
internal medicine and vaccines. Sanofi-aventis is listed in
Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

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Statement Regarding Forward-Looking Statements" in
sanofi-aventis' annual report on Form 20-F for the year
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information or statements.

    1. Samama.New England Journal of Medicine.Sept.1999.

    2. Bergqvist New England Journal of Medicine March
2002/ Vol 346, No.13.

    3. Hull, Ann Intern Med.2001; 135:858-869.

    4. Geerts.Chest.2004.


    For more information, please contact:

     Philippe BARQUET 
     Tel:  [phone]