LONDON, September 17 /PRNewswire/ -- The National Institute for Health and Clinical Excellence (NICE) has today issued a Final Appraisal Determination ('FAD') that recommends ezetimibe for the treatment of high cholesterol in certain patients: the document confirms that ezetimibe can be used in combination with a statin in patients whose cholesterol levels remain above national targets, even with a low cholesterol diet and the use of initial statin therapy which has been titrated appropriately(1); the therapy can also be taken on its own ('monotherapy') by patients who can not take a statin because of intolerance or contraindication.(1)

The NICE Committee highlights that the UK population has one of the highest average cholesterol concentrations in the world.(1) It adds that cardiovascular disease is the most common cause of death in the UK, accounting for approximately 216,000 deaths in 2004, and it is a major cause of illness, disability and reduced quality of life.(1)

Michael Livingston, Director, H.E.A.R.T. UK, commented "We are delighted with the decision made by NICE to recommend ezetimibe in England and Wales. The impact of high cholesterol is huge and too many patients are still being put at risk of premature death - over 4,000 people die every week of cardiovascular disease in the UK because of high cholesterol, smoking, physical inactivity and poor diet. Prescribing ezetimibe will be of great benefit to those who currently find it very difficult to reach their cholesterol target."

How the therapy works

There are two main sources of cholesterol in our blood - cholesterol absorbed from the intestine(i) and cholesterol made in the liver.(ii),(2) Ezetimibe has a unique mode of action as it selectively blocks the absorption of cholesterol in the intestine, even in those patients who are already on a low cholesterol diet.(2) When ezetimibe is combined with a statin, there is a 'dual inhibition' of the two main sources of cholesterol in the body: the statin inhibiting cholesterol production in the liver and ezetimibe inhibiting cholesterol absorption from the intestine.(2)

Reaching recommended cholesterol levels

National guidelines recommend a total cholesterol target of less than 5 mmol/l (millimoles per litre) and a 'bad' cholesterol (LDL-C) target of less than 3 mmol/l.(3) However, despite the availability of effective medications, about 35% of patients with coronary heart disease are not reaching these targets.(4)

Dr John Pittard, a GP from Staines in Surrey, commented "Primary care treats thousands of high risk patients to reduce their cholesterol. Many patients don't fully respond or tolerate statins - ezetimibe is really useful in these cases and doctors will welcome this sensible advice from NICE."

Today's FAD guidance states that adding ezetimibe to initial statin therapy as a treatment option is a cost-effective choice for patients who have not reached national targets, when compared with switching to an alternative statin.(1) The guidance also states that doctors may add ezetimibe when appropriate dose titration is limited by intolerance to the initial statin therapy.(1) The 'FAD' defines intolerance to statin therapy as the presence of clinically significant adverse effects from statin therapy that are considered to represent an unacceptable risk to the patient or that may result in compliance with therapy being compromised.(1)

Ezetimibe is licensed to treat high cholesterol - either inherited (familial heterozygous hypercholesterolemia) or not inherited (non-familial primary hypercholesterolemia) - in patients who have already been prescribed a statin and whose cholesterol levels remain uncontrolled.(5)

Implementation of the NICE HTA Guidelines

The recommendation issued today forms the basis of the final ezetimibe guidance for the NHS in England and Wales, which is expected to be formally issued in November. Within 3 months of this formal guidance publication, the NHS is required by the Secretary of State to provide funding and resources for medicines and treatments recommended through this appraisal process.(1)

Notes to Editors

The increasing burden of cardiovascular disease (CVD)

- CVD is the main cause of death in the UK accounting for just over 216,000 deaths a year.1 Nearly half of these deaths are from coronary heart disease (CHD) - the result of atherosclerosis of the arteries surrounding the heart.(6)

- CVD is also one of the main causes of premature death in the UK (death before the age of 75). 31% of premature deaths in men and 23% of premature deaths in women are from CVD.(6)

Cholesterol and the reduction of cardiovascular risk

- Cholesterol is one of the most important risk factors for CHD(7) and raised LDL cholesterol is related to an increase in cardiovascular risk.(8)

- There is no set 'normal' range for blood lipid concentrations due to population variation, but the UK currently has one of the highest average cholesterol concentrations in the world.(1)

About Merck Sharp & Dohme and Schering-Plough

- Merck Sharp & Dohme Limited and Schering-Plough Limited are partners in the development and marketing of prescription medicines in cholesterol management.

- Merck Sharp & Dohme Limited is the UK subsidiary of Merck & Co. Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.

- Schering-Plough is a global science-based healthcare company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of physicians, patients and customers served by its more than 33,500 people around the world.

EZETROL(R) is a registered trademark of MSP Singapore Company, LLC.

References

(i) Estimated to be 1000 mg per day total, composed of dietary (300 mg per day) and biliary (700 mg per day)2

(ii) Estimated to be 800 mg per day8

(1) National Institute for Health and Clinical Excellence (NICE). Final Appraisal Documentation for Ezetimibe in hypercholesterolaemia: http://guidance.nice.org.uk/

(2) Shepherd J. The role of the exogenous pathway in hypercholesterolaemia. Eur Heart J Suppl, 2001:3. Suppl. C: E2-E5.

(3) Department of Health, National Service Framework for Coronary Heart Disease, 2000. London: DoH

(4) Brady AJB, Norrie J, Ford I. Statin prescribing: is the reality meeting the expectations of primary care? Br J Card 2005;12:397-400.

(5) Ezetrol Summary of Product Characteristics, http://emc.medicines.org.uk/ (Accessed 08.08.07)

(6) British Heart Foundation. Coronary Heart Disease statistics. 2007 edition

(7) British Heart Foundation - Any Questions? LDL Apheresis for familial hypercholesterolaemia. http://www.bhf.org.uk/faqs.aspx?qid=7820. (Accessed on 08.05.07)

(8) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at: www.nhlbi.nih.gov/guidelines/cholesterol/index.htm

Media Contacts: Annabel Cowper, Chandler Chicco Agency, 151 Shaftesbury Avenue, London, WC2H 8AL, +44-207-632-1813, +44(0)7776-188-166; Harry Brady, Merck Sharp & Dohme, Hertford Road, Hoddeson, Hertfordshire, EN11 9BU, +44(0)1992-452-134, +44(0)7974-444-431; Mindy Dooa, Schering Plough, Falcon Way, Shire Park, Welwyn Garden City, ALZ 1TW, +44(0)1707-363-983, +44(0)7917-553-253