25.06.2013 – 10:25
23rd European Meeting on Hypertension and Cardiovascular Protection
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
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
(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.
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