New Indication for Procoralan(R): Use in Combination With Beta Blockers for Chronic Stable Angina Patients

PARIS, December 15 - The European Medicines Agency (EMEA) has recently approved a new
indication for Procoralan*(ivabradine). Procoralan can now be administered to
chronic stable angina patients, who remain inadequately controlled despite an
optimal dose of beta blockers, and whose heart rate is above 60 beats per
minute.

In October 2005, Procoralan was approved by the EMEA for
clinical use in symptomatic treatment of chronic stable angina patients in
sinus rhythm, unable to tolerate or with a contraindication to the use of
beta blockers. Subsequently a great deal of new information concerning the
clinical benefits of Procoralan has been published. In particular, the
results of ASSOCIATE(1) and the BEAUTIFUL trial(2) have influenced the change
in indication.

The results of the ASSOCIATE trial performed in 889 patients
showed that Procoralan, given on top of atenolol 50 mg o.d, showed additional
efficacy on all exercise tolerance test (ETT) parameters at trough of drug
activity. The results of this trial have particular significance because
despite the fact that combination therapy is widely used in clinical practice
to achieve adequate control of angina, clinical trials evaluating combination
therapy have yielded inconsistent results. "The ASSOCIATE study, in terms of
the size of the trial, the compliance with regulatory recommendations, and
the consistency of significant improvements across all ETT criteria and time
points, represents perhaps the most compelling single demonstration of the
benefit of any combination of anti-anginal drugs published to date," said the
study lead investigator Dr Jean-Claude Tardif, from the Montreal Heart
Institute in Canada.

BEAUTIFUL was a large outcome study done in 10917 patients with coronary
artery disease and left ventricular dysfunction (LVEF <42%) on top of optimal
background therapy with 86.9% of patients receiving beta-blockers. A specific
analysis in patients with limiting angina showed that patients on Procoralan
had a lesser risk of having a heart attack, of getting admitted to hospital
for heart failure or cardiovascular death (Procoralan 12% versus placebo
15.5%, p=0.05).

Procoralan was well tolerated in both these studies. ASSOCIATE
and BEAUTIFUL have been mentioned in the new updated summary of product
characteristics.

"Procoralan has proven anti-anginal efficacy and may also prevent
cardiovascular events in angina patients. This new indication will permit us
to better treat the large number of chronic stable patients who remain
uncontrolled despite receiving a beta blocker," comments Prof K Fox from the
Royal Brompton hospital, UK who has participated in several clinical trials
on Procoralan.

Issued by Servier, France's leading independent pharmaceutical company.

*Depending on the country, ivabradine is available as Procoralan(R),
Coralan(R), Coraxan(R), or Corlentor(R)

References

(1) Tardif JC, Ponikowski P, Kahan T; ASSOCIATE study
investigators. Efficacy of the If current inhibitor ivabradine in
patients with chronic stable angina receiving beta blocker therapy: a 4
month, randomized, placebo-controlled trial. Eur Heart J.
2009;30:540-548.

(2) Fox K, Ford I, Steg PG, et al. On behalf of the BEAUTIFUL
investigators. Relationship between ivabradine treatment and
cardiovascular outcomes in patients with stable coronary artery disease
and left ventricular systolic dysfunction with limiting angina: a
subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur
Heart J 1.Eur Heart J 2009;30, 2337-2345.

For further information, please contact: Monica Gounaropoulos, Tonic Life Communications (Tel. +44-20-7798-9910) monica.g at toniclc.com