Late-Breaking Analysis in Hypertension Shows That Antihypertensive Treatments Differ in Their Ability to Preserve Lives

STOCKHOLM, August 30, 2010 - According to the results of a late-breaking analysis involving more than
200 000 patients who participated in recent clinical trials, antihypertensive
treatments with renin-angiotensin system (RAS) inhibitors significantly
differ in their ability to preserve lives.(1) This new analysis, presented
today at the European Society of Cardiology (ESC) Congress, revealed that
patients receiving a treatment including a RAS inhibition with perindopril
had a significantly greater improvement in life expectancy.

"The goal of hypertension management is not only to reduce blood pressure
and cardiovascular events, but also to reduce deaths", says study
co-investigator Professor Michel Bertrand (1). "The benefits of RAS
inhibition for the reduction of cardiovascular morbidity as stroke or
myocardial infarction (for ACE inhibitors) is well established. However, the
impact on mortality is less well known."

The analysis reviewed 21 international morbidity-mortality trials*
performed over the last decade and principally including hypertensive
patients (ie, more than 2/3 of the randomized population in each trial and
excluding heart failure studies). Only three treatment strategies evaluated
in three trials (ASCOT-BPLA, ADVANCE, and HYVET) demonstrated significant
reductions in death from all causes. In each of these three landmark trials,
perindopril alone or in combination was in the active treatment arm, making
it the antihypertensive with most evidence-based data on mortality reduction.
None of the 18 remaining trials demonstrated a significant reduction in
mortality, whatever the treatment analyzed.

Combining the results of ASCOT, ADVANCE, and HYVET led to a significant
13% reduction in all-cause mortality (p< 0.001). In contrast, combining the
results of the 18 trials excluding perindopril demonstrated absolutely no
impact on mortality (HR : 0.99, p=0.472), even when pooling more than 160 000
patients.

"As this difference in all-cause mortality is not explained by the level
of risk of the patients, by their age or blood pressure, or by the duration
of the studies, our hypothesis is that it is related to a specific effect of
the active treatments used in these trials", points out Professor Michel
Bertrand. "Perindopril was the only agent used in all three trials, the
diuretic indapamide was used twice, in ADVANCE and HYVET, and the calcium
channel blocker amlodipine once, in ASCOT."

"It is important that the effect of a specific antihypertensive on
mortality reduction be taken into account when considering the treatment of
hypertension patients, particularly those at high risk."

Notes to editor:

*The 21 clinical trials analyzed were IDNT, RENAAL, ALLHAT, LIFE, INVEST,
ANBP-2, SCOPE, VALUE, JMIC-B, ASCOT-BPLA, MOSES, JIKEI, ADVANCE, HYVET,
ONTARGET, TRANSCEND, PROFESS, ACCOMPLISH, KYOTO, NAVIGATOR.

Perindopril is licensed worldwide for treatment of hypertension, coronary
artery disease, and heart failure under the trade names COVERSYL(c),
COVEREX(c), ACERTIL(c), PRESTARIUM(c), PREXANIL(c), PREXUM(c), COVERENE(c),
COVERSUM(c), PROCAPTAN(c) and ACEON(c)

ADVANCE Action in Diabetes and Vascular disease: PreterAx and DiamicroN
MR Controlled Evaluation) was designed, conducted, monitored, analyzed, and
reported by a collaborative medical research group supported by the
Australian Government's National Health and Medical Research Council after
full peer review.

The first part of ADVANCE investigated the effects of intensive blood
pressure lowering on outcome using a fixed combination of perindopril and
indapamide (Preterax(R)). It showed that the routine administration of a
fixed combination of perindopril and indapamide improves survival and reduces
the risk of heart and kidney disease.(2)

ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure-Lowering Arm) was a major multinational trial, endorsed by the
British Hypertension Society, involving over 19 000 hypertensive patients. It
compared the effectiveness of two different treatment strategies at reducing
cardiovascular events. The newer treatment strategy (amlodipine and
perindopril) offered such significant advantages over the older treatment
strategy (atenolol and bendroflumethiazide) that the trial was stopped early
by the Data Safety Monitoring Board in December 2004.(3)

HYVET (HYpertension in the Very Elderly Trial) was an international,
placebo-controlled trial looking at the benefits of giving blood
pressure-lowering medication (low-dose indapamide SR and perindopril) once
daily to elderly patients. It was stopped early, after researchers observed
significant reductions in overall mortality in those receiving treatment.(4)

HYVET was the largest trial to look at the effects of lowering blood
pressure solely in those aged 80 and over. The trial results suggest that
lowering blood pressure significantly reduces both stroke and mortality in
the over-80s. HYVET was coordinated by Imperial College London, working with
colleagues around the world. The trial was funded by both the British Heart
Foundation and Servier.

References

1) JJ Mourad, M Bertrand. Impact of antihypertensive treatment
on mortality: A late-break analysis of recent clinical trials in
hypertension. Abstract ESC 2010.

2) ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, et al.
Effects of a fixed combination of perindopril and indapamide on macrovascular
and microvascular outcomes in patients with type 2 diabetes mellitus (the
ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829-840.

3) Dahlof B, Sever PS, Poulter NR, et al. Prevention of
cardiovascular events with an antihypertensive regimen of amlodipine
adding perindopril as required versus atenolol adding bendroflumethiazide
as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled
trial. Lancet 2005;366:895-906.

4) Beckett NS, Peters R, Fletcher A, et al. Treatment of
hypertension in patients 80 years of age and older. N Engl J Med
2008;358.