23rd European Meeting on Hypertension and Cardiovascular Protection

München (ots) -

New data from the SEVITENSION study show the fixed-dose
combination treatment Sevikar® (olmesartan/amlodipine) to be
superior to perindopril in combination with amlodipine in reducing
central blood pressure

When the traditional arm (brachial) method of measurement is used,
blood pressure is usually found to be higher than it is in the large
central arteries.(1) Central blood pressure is believed to provide a
more accurate reflection of the pressure experienced by the internal
organs,(1) and there is an increasing amount of evidence from
clinical studies to show that measures of central blood pressure
predict damage to organs and the risk of disease- related events more
accurately than brachial blood pressure.(2-4) The Conduit Artery
Function Evaluation (CAFÉ) study, a substudy of the ground-breaking
ASCOT study, showed that the treatment combinations used had
different effects on central systolic aortic blood pressure, with a
significant advantage for the perindopril and amlodipine
combination.(5) "According to the investigators of the study, this
advantage could potentially explain the differences in clinical
outcomes between the two groups in the ASCOT study.(6) These findings
are what inspired the SEVITENSION study" explained Professor Luis
Ruilope, Head of the Hypertension Unit at 12 de Octubre Hospital,
Madrid, Spain and Principal Investigator of the Sevitension study.
"Post-marketing studies like these provide important insights to help
physicians select the best treatment options to manage hypertension
more effectively and conveniently and protect patients in a better
way. And this potentially improved management will help achieve the
ambitious goal of controlling the blood pressure (<140/90 mmHg) of
70% of hypertension patients by 2015."

Drugs like angiotensin-converting enzyme inhibitors (ACEIs) lower
blood pressure by inhibiting the activity of the renin-angiotensin
system (RAS). Another class of antihypertensive drugs known as
angiotensin receptor blockers (ARBs) also lowers blood pressure by
inhibiting the RAS, and offers the advantage of fewer side effects
than ACEIs, in particular cough.(7)

Daiichi Sankyo actively supports research into treatments for
hypertension and has developed a range of treatments based upon the
ARB olmesartan. One of these treatments, a dual combination of
olmesartan with amlodipine (Sevikar®), has now been used to address
an important clinical question: can a dual combination of an ARB like
olmesartan plus amlodipine lower central blood pressure as
effectively as perindopril plus amlodipine? This question was
addressed by the SEVITENSION study,(8) and the first findings from
this study were revealed at an ESH 2013 poster session. (10)

SEVITENSION set out to show that olmesartan 40 mg/amlodipine 10 mg
was non inferior to perindopril 8 mg/amlodipine 10 mg, the treatment
used in the CAFÉ study, in lowering central blood pressure. The
results show not only that this aim was achieved, but also that the
reductions in central blood pressure went beyond this and met the
criteria of a test for superiority defined by the European Agency for
the Evaluation of Medicinal Products.(9) This means that olmesartan
40 mg/amlodipine 10 mg was shown to be superior to perindopril 8
mg/amlodipine 10 mg.(10) Other secondary endpoints including
standard brachial blood pressure and ambulatory blood pressure
measurements made over 24 hours also confirmed that olmesartan 40
mg/amlodipine 10 mg was superior. Another important finding was that
three quarters (75.6%) of patients treated with olmesartan 40
mg/amlodipine 10 mg were able to 'normalise' their blood pressure(10)
so that it fell below the level (<140/90 mmHg) recommended by the
European Society of Hypertension for all patients with
hypertension.11 The proportion of patients who achieved this level of
blood pressure with the perindopril 8 mg/amlodipine 10 mg combination
was nearly 20% lower (57.5%). "The gold standard since the
publication of the CAFÉ study has been the combination of perindopril
8 mg/amlodipine 10 mg and we compared this with olmesartan 40
mg/amlodipine 10 mg which lowered central blood pressure levels
significantly more. The better the response of blood pressure the
lower could be the chance of suffering cardiovascular events,"
commented Professor Luis Ruilope, the lead investigator of the
SEVITENSION study.

NOTES TO EDITORS

About Sevikar

Sevikar is a fixed-dose combination of olmesartan and
amlodipine:(12)

- Olmesartan is an angiotensin II receptor antagonist or blocker
(ARB) which works by inhibiting the action of the RAS by
blocking the action of a hormone called angiotensin-II.
Angiotensin-II causes blood vessels to narrow
(vasoconstriction) and leads to the production of another
hormone called aldosterone which is responsible for fluid
retention. By preventing the action of angiotensin-II,
olmesartan widens blood vessels and reduces fluid in the blood
lowering the blood pressure.

- Amlodipine is a long-acting calcium channel blocker indicated to
reduce blood pressure. Amlodipine acts by relaxing the smooth
muscles in artery walls decreasing total peripheral resistance
and hence reducing blood pressure.

About Combination Therapy (According to the European Guidelines on
Hypertension Management)(11)

Several two-drug combinations are suitable for clinical use.
However, trial evidence of outcome reduction has been obtained
particularly for the combination of a diuretic with an ACE inhibitor
or an angiotensin receptor antagonist or a calcium antagonist, and in
recent large-scale trials for the ACE inhibitor/calcium antagonist
combination. The angiotensin receptor antagonist/calcium antagonist
combination also appears to be rational and effective.(11)

In no less than 15-20% of hypertensive patients, BP control cannot
be achieved by a two-drug combination. When three drugs are required,
the most rational combination appears to be a blocker of the
renin-angiotensin system, a calcium antagonist, and a diuretic at
effective doses.(11)

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address the diversified, unmet
medical needs of patients in both mature and emerging markets. While
maintaining its portfolio of marketed pharmaceuticals for
hypertension, hyperlipidemia, and bacterial infections, the Group is
engaged in the development of treatments for thrombotic disorders and
focused on the discovery of novel oncology and
cardiovascular-metabolic therapies. Furthermore, the Daiichi Sankyo
Group has created a "Hybrid Business Model," which will respond to
market and customer diversity and optimise growth opportunities
across the value chain. For more information, please visit:
www.daiichisankyo.com

About Daiichi Sankyo Europe

Daiichi Sankyo?s European base is located in Munich and has
affiliates in 12 European countries in addition to a global
manufacturing site located in Pfaffenhofen, Germany. For more
information, please visit: www.daiichi-sankyo.eu

References

(1) Sharman, J. E. & Laurent, S. Central blood pressure in the
management of hypertension: soon reaching the goal? J Hum
Hypertens 27, 405-411, (2013).
(2) Pini, R. et al. Central but not brachial blood pressure
predicts cardiovascular events in an unselected geriatric
population: the ICARe Dicomano Study. J Am Coll Cardiol 51,
2432-2439, (2008).
(3) Vlachopoulos, C. et al. Prediction of cardiovascular events
and all-cause mortality with central haemodynamics: a
systematic review and meta-analysis. Eur Heart J 31,
1865-1871, (2010).
(4) Agabiti-Rosei, E. et al. Central blood pressure measurements
and antihypertensive therapy: a consensus document.
Hypertension 50, 154-160, (2007).
(5) Williams, B. et al. Differential impact of blood pressure-
lowering drugs on central aortic pressure and clinical
outcomes: principal results of the Conduit Artery Function
Evaluation (CAFE) study. Circulation 113, 1213-1225, (2006).
(6) Dahlof, B. 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 366, 895-906, (2005).
(7) Yusuf, S. et al. Telmisartan, ramipril, or both in patients
at high risk for vascular events. N Engl J Med 358,
1547-1559, (2008).
(8) Ruilope, L. M. & Schaefer, A. Efficacy of Sevikar® compared
to the combination of perindopril plus amlodipine on central
arterial blood pressure in patients with moderate-to-severe
hypertension: Rationale and design of the SEVITENSION study.
Contemp Clin Trials 32, 710-716, (2011).
(9) European Agency for the Evaluation of Medicinal Products,
Committee for proprietary medicinal products (CPMP). Points
to consider on switching between superiority and
non-inferiority (CPMP/EWP/482/99). http://www.emea.europa.eu/
docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003658.
pdf

(10) Ruilope, L on behalf of the SEVITENSION Study Investigators.
The fixed combination olmesartan/amlodipine was superior in
reducing central aortic blood pressure compared to
perindopril with amlodipine. (Poster presentation session P26
at the 23rd European Meeting on Hypertension & Cardiovascular
Protection; Milan, Italy, Sunday 16 June 2013).
(11) Mancia, G. et al. Reappraisal of European guidelines on
hypertension management: a European Society of Hypertension
Task Force document. J Hypertens 27, 2121-2158, (2009).
(12) Daiichi Sankyo Europe GmbH. Sevikar Summary of Product
Characteristics 2012.

Contact:
Product Communications
Lydia Worms European
Phone +49 89 7808 751
lydia.worms@daiichi-sankyo.eu