Each study is combining the highly effective statin CRESTOR (rosuvastatin) with cutting-edge imaging technology: intravascular ultrasound (IVUS)1 or magnetic resonance imaging (MRI)2,3; to evaluate whether CRESTOR can slow the progression or even lead to a regression of atherosclerosis.
Atherosclerosis gradually narrows the blood vessels, which can lead to a reduction in blood supply to vital organs such as the brain and heart, in some cases this can lead to angina and even a stroke or heart attack. A number of studies have shown that statins may slow the progression or even cause regression of atherosclerosis.4-7 Lowering LDL-cholesterol (LDL-C) slows the progression of atherosclerosis, however, it has been suggested that a larger reduction of at least 40% in LDL-C is needed to observe a regression of atherosclerosis.8,9
Treatment of atherosclerosis should be considered an important target as clinical studies have shown that <1% regression of coronary atherosclerosis is associated with major (70-80%) reductions in clinical events such as heart attacks.10
"Patients with atherosclerosis can show no symptoms for years before experiencing a serious, sometimes fatal, cardiovascular event – often making this disease a silent killer," explained Professor Gunnar Olsson, Vice President and Head of Cardiovascular Therapy Area, AstraZeneca.
"We know that raised LDL-C (or bad cholesterol) and low levels of HDL-C (or good cholesterol) are major risk factors for atherosclerosis and coronary heart disease. CRESTOR can reduce LDL-cholesterol significantly more than the same and some higher doses of other widely used statins and also provides the added benefit of raising HDL-cholesterol or good cholesterol. The three ongoing studies, ASTEROID, ORION and METEOR will demonstrate the benefits of CRESTOR on the atherosclerotic disease process thereby offering the potential for improving the prognosis of patients with, or at risk of, cardiovascular disease – the world's number one killer."
ASTEROID1 and ORION2, 3, 11 are the first studies to evaluate CRESTOR 40mg – which has been shown to reduce LDL-C by up to 63%12 – on atherosclerosis using the novel imaging technologies IVUS and MRI.
Dr. Steven Nissen, Medical Director of the Cardiovascular Coordinating Center at the Cleveland Clinic Foundation, USA, is the principal investigator on the ASTEROID study. He commented: "Current imaging technology, such as coronary angiography, has only allowed us to visualise the narrowing of the blood vessel caused by atherosclerosis. IVUS lets us see the equally dangerous atherosclerosis hidden within the vessel wall. We are visualising not just the tip of the iceberg, but also what is below the waterline. CRESTOR, compared to other statins, provides outstanding efficacy both in terms of reducing LDL-C (bad cholesterol) and raising HDL-C (good cholesterol). ASTEROID will determine if a maximum dose (40mg) of this particular agent can actually reduce the burden of coronary atherosclerosis during two years of treatment."
"By using non-invasive MRI in ORION we will be able to measure the exact shape, size and distribution of atherosclerosis in blood vessels which may enable us to better evaluate the vascular effects of lipid-lowering therapy, and in clinical practice the use of MRI could facilitate early diagnosis and treatment," stated Dr. Baocheng Chu of the University of Washington School of Medicine, Seattle and investigator for ORION. He continued, "ORION will also show the benefits of CRESTOR in hypercholesterolaemic patients with established atherosclerotic disease."
ASTEROID, which started in November 2002, will recruit 450 patients with coronary artery disease from approximately 60 centres worldwide who will be treated with CRESTOR 40mg once daily for 24 months. The study will measure the percentage change in coronary artery volume at the end of treatment using IVUS. Coronary atherosclerosis will also be assessed using quantitative coronary angiography. 1
ORION has completed recruitment and 39 hypercholesterolaemic patients with established atherosclerosis have been randomised to receive CRESTOR 5mg or 40mg for 24 months. Baseline measurements from patients enrolled in the study were announced at ISA. The change in bilateral carotid artery wall volume will be measured by using MRI. Changes in the intima media thickness of the carotid arteries will also be measured using B-mode ultrasound. 2, 3, 11
METEOR is the third study within the GALAXY Programme evaluating the effects of CRESTOR on atherosclerosis.13 The study which started in August 2002 is using B-mode ultrasound to compare the effects of CRESTOR 40mg or placebo on intima media thickness of the carotid arteries in 840 asymptomatic patients with sub-clinical atherosclerosis who are not routinely treated with statin medication.
CRESTOR has now received regulatory approvals across three continents; America, including the USA, Europe and Asia, and has been launched in several countries worldwide. CRESTOR is awaiting approval in a number of other countries over the coming months.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $17.8 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.
AstraZeneca has more than 40 years experience in cardiovascular medicine and aims to increase lifespan and improve quality of life by reducing the risk, prevalence and impact of cardiovascular disease. AstraZeneca has a comprehensive cardiovascular portfolio including CRESTORTM, ATACANDTM, ZESTRILTM, TENORMINTM, SELOKEN ZOK /TOPROL-XLTM and PLENDILTM. This heritage is complemented by an innovative pipeline including the first oral direct thrombin inhibitor, EXANTATM, and a novel treatment for type 2 diabetes / metabolic syndrome, GALIDATM.
For further information please visit: http://www.AstraZenecaPressOffice.com.
Contact:
Julia Walker, Global PR Manager, Cardiovascular Therapy Area, AstraZeneca
Tel: 44-0-1625-510866
Mobile (in Japan): 81-0-90-5340-2294
Mobile: 44-0-7718-80-1984
Email: julia.walker@astrazeneca.com
Ellie Goss or Stephanie Martin, Shire Health International
Tel: 44-0-20-7471-1500
Ellie Goss's mobile (in Japan): 81-0-90-5340-4799
Email: .goss@shirehealthinternational.com
Notes to Editor:
The GALAXY Programme
The GALAXY Programme is a large, comprehensive, long-term, and evolving global research initiative sponsored by AstraZeneca to investigate cardiovascular risk reduction and patient outcomes with CRESTOR. Please refer to the GALAXY media backgrounders for more information on the GALAXY Programme and each of the individual GALAXY Programme studies.
Cardiovascular disease
The term cardiovascular disease (CVD) refers to a wide range of disorders affecting the heart and blood vessels. The main manifestations of CVD are coronary heart disease (CHD) (heart attacks, angina and arrhythmias), cerebrovascular disease (strokes and transient ischaemic attacks) and peripheral vascular disease (intermittent claudication).
CVD is estimated to account for a third of all deaths globally and is the leading cause of mortality in Europe and the US. Over 16.5 million deaths each year are due to CVD (more than 45,000 deaths every day, and almost 32 deaths each minute).14 In Europe, about half of all deaths from CVD are from CHD and nearly one-third are from stroke.15
For more information please refer to the media backgrounders, 'Atherosclerosis', 'Cardiovascular disease and its risk factors', 'GALAXY Programme' and 'GALAXY Programme studies', which can be found on: http://www.AstraZenecaPressOffice.com
Additional data at ISA
AstraZeneca will be presenting additional CRESTOR studies during ISA, including:
MERCURY I (Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY)
- Barter P, Stender S, Morrell J et al. Switching to rosuvastatin from other statins has beneficial effects on Apo B and the Apo B:Apo A-1 ratio. Results from the MERCURY I Trial. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Schuster H, Cheung R, Bonnet J et al. Switching to rosuvastatin from other statins has beneficial effects on lipid ratios. Results from the MERCURY I Trial. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Monday 29th September, 13.00-15.00.
STELLAR (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin)
- Stein E, Jones P, Deedwani P et al. Rosuvastatin compared with atorvastatin, simvastatin, and pravastatin for lipid ratios. Results from the STELLAR Trial. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Stein E, Jones P, Rhyne J et al. Rosuvastatin improves apolipoproteins A-1 and B more than atorvastatin, simvastatin and pravastatin. Results from the STELLAR Trial. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Tuesday 30th September, 13.00-15.00.
Abstracts will be available online at http://www.congre.co.jp/isa and once these data have been presented media materials will be available on http://www.AstraZenecaPressOffice.com.
References:
1. Nissen S. Design and methodology of A Study To evaluate the Effect of Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden: the ASTEROID study. 13th International Symposium on Atherosclerosis, Kyoto, Japan, 2003.
2. Chu B, Hatsukami TS, Polissar NL et al. Use of Magnetic Resonance Imaging to Assess Carotid Atherosclerotic Lesion Distribution. 13th International Symposium on Atherosclerosis, Kyoto, Japan, 2003.
3. Chu B, Hatsukami TS, Zhao X et al. Reproducibility of Carotid Atherosclerotic Lesion Type Determination Using High-Resolution Magnetic Resonance Imaging. 13th International Symposium on Atherosclerosis, Kyoto, Japan, 2003.
4. Crouse JR 3rd, Byington RP, Bond MG et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II). Am J Cardiol 1995;75:455–459.
5. de Groot E, Jukema JW, van Swijndregt ADM et al. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: A report of the Regression Growth Evaluation Statin Study (REGRESS). J Am Coll Cardiol 1998;31:1561–1567.
6. Hodis HN, Mack WJ, LaBree L et al. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy. Ann Intern Med 1996;124:548–556.
7. MacMahon S, Sharpe N, Gamble G et al. Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group. Circulation 1998;97:1784–1790.
8. Thompson GR. What targets should lipid-modulating therapy achieve to optimise the prevention of coronary heart disease? Atherosclerosis 1997 Jan 16;131(1):1-5.
9. Smilde TJ, van Wissen S, Wollersheim H et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001;357:577–581.
10. Brown BG, Albers JJ, Fisher LD et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990 Nov. 8;323(19):1289-1298.
11. Hatsukami TS, Zhao XQ, Yuan C et al. Study design for a randomized, double-blind trial to assess the effect of 24 months of dosing with rosuvastatin on progression of carotid artery atheroma in moderately hypercholesterolemic patients with asymptomatic carotid stenosis. Atherosclerosis Supplements 2001;2(2):47-8, Abs P4.
12. Olsson AG, McTaggart F, Raza A. Rosuvastatin: A highly effective new HMG-CoA reductase inhibitor. Cardiovasc Drug Reviews 2002;20:303–328.
13. Crouse III JR, Grobbee DE, O'Leary DH et al. Measuring effects on intima media thickness: an evaluation of rosuvastatin - the METEOR study. Atherosclerosis Supplements 2002;3(2):94 Abs 136.
14. World Health Report 2002. World Health Organization. http://www.who.int.
15. Rayner M and Petersen S. European cardiovascular disease statistics. BHF: London 2000. http://www.heartstats.org.
ORION = Outcome of Rosuvastatin treatment on carotid artery atheroma: a Magnetic Resonance Imaging Observation
ASTEROID = A Study To Evaluate Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden
METEOR = Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin
CRESTOR and GALAXY Programme are trade marks of the AstraZeneca group of companies
For more information please see www.AstraZenecaPressOffice