LDL-cholesterol (LDL-C or 'bad' cholesterol), the principle atherogenic lipoprotein, remains the primary target for international and national guidelines aimed at lowering cardiovascular risk.5, 6 The protein components of lipoproteins are called apolipoproteins and, although currently not often measured in clinical practice, the amounts of apolipoproteins circulating in the blood are directly related to the levels of corresponding lipoproteins and may be a more useful predictor of cardiovascular disease (CVD) risk.7, 8 Raised levels of apolipoprotein A-I (Apo A-I) are linked to an increase in HDL levels, which is associated with a decreased risk of atherosclerosis,9,10 whereas apolipoprotein B (Apo B) has been suggested to be a better marker of CVD risk than total cholesterol (TC) or LDL-C because it more accurately reflects the presence of all atherogenic lipoproteins.7,8,11,12 Assessment of the ratio of lipids or apolipoproteins may provide a refined assessment of CVD risk as it reflects the proportion of both atherogenic and cardioprotective lipids or apolipoproteins.7,8, 11-13
Data presented from the STELLAR study show that CRESTOR 10-40mg has more favourable effects on the atherogenic Apo B, the cardioprotective Apo A-I, and the Apo B:Apo A-I ratio in patients with hypercholesterolaemia than the same and some higher doses of atorvastatin, simvastatin and pravastatin.1 CRESTOR 10mg also had a significantly more favourable effect on the Apo B:Apo A-I ratio (p<0.002) than atorvastatin 10mg, simvastatin 10-40mg and pravastatin 10-40mg.1 Similar results were also observed for other lipid ratios (TC:HDL-C and non-HDL-C:HDL-C) considered to be important predictors of CVD risk.2
These important benefits are supported by data presented from the MERCURY I study, showing those patients who switched to CRESTOR 10mg had a significantly greater reduction (p<0.001) in their Apo B, Apo B:Apo A-I ratio and other lipid ratios (TC:HDL-C; non-HDL-C:HDL-C and LDL-C:HDL-C) than those who remained on atorvastatin 10mg, simvastatin 20mg or pravastatin 40mg.3,4
Lead investigator for the STELLAR prospective planned analysis, Dr Evan Stein, Metabolic & Atherosclerosis Research Center, Cincinnati, Ohio commented: "A number of recent prospective and intervention studies have clearly demonstrated the enhanced ability of apolipoproteins and lipid ratios in predicting cardiovascular risk. It is therefore important for clinicians to be able to assess the efficacy of various treatments on these important markers. These studies clearly show the enhanced ability of CRESTOR to improve key apolipoproteins and lipid ratios, and these new data reinforce the excellent efficacy of CRESTOR in reducing LDL-C and raising HDL-C in patients who have had, or are at risk of, serious cardiovascular events."
On behalf of the MERCURY I study group, Professor Philip Barter, The Heart Research Institute, Sydney, Australia: continued: "Taken together data from these two studies show the superior benefits that CRESTOR offers doctors in managing patients' lipid ratios to successfully reduce the burden of cardiovascular disease."
The STELLAR and MERCURY I studies form part of AstraZeneca's comprehensive GALAXY ProgrammeTM.
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, anaesthesia (including pain management), cardiovascular, central nervous system (CNS) 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: 44-0-162-551-0866
Mobile (in UK): 44-0-771-880-1984
Mobile (in Japan): 81-0-90-5340-2294
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: ellie.goss@shirehealthinternational.com
Notes to Editor:
MERCURY I (Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY)
MERCURY I was a 16-week, randomised, open-label, multinational, phase IIIb parallel-group switching study that compared the efficacy of CRESTOR versus atorvastatin, pravastatin and simvastatin in patients with type IIa or IIb hypercholesterolaemia (the most common forms of hypercholesterolaemia) and established atherosclerosis, coronary heart disease or type 2 diabetes. MERCURY I was carried out in 3,161 patients from 224 centres in 15 countries. There were five treatment arms:
- CRESTOR 10mg for 16 weeks
- Atorvastatin 10mg for 16 weeks OR atorvastatin 10mg for 8 weeks followed by CRESTOR 10mg for 8 weeks
- Atorvastatin 20mg for 16 weeks OR atorvastatin 20mg for 8 weeks followed by CRESTOR 10mg for 8 weeks OR atorvastatin 20mg for 8 weeks followed by CRESTOR 20mg for 8 weeks
- Simvastatin 20mg for 16 weeks OR simvastatin 20mg for 8 weeks followed by CRESTOR 10mg for 8 weeks
- Pravastatin 40mg for 16 weeks OR pravastatin 40mg for 8 weeks followed by CRESTOR 10mg for 8 weeks
STELLAR (Statin Therapies for Elevated Lipid Levels compared Across dose ranges to Rosuvastatin)
STELLAR was designed as a six-week, randomised, multi-centre, parallel-group, 15-arm, open-label study in 2,431 hypercholesterolaemic patients from 183 centres across the US. The study period was preceded by a six-week dietary lead-in period.
The GALAXY Programme
The GALAXY Programme is a large, comprehensive, long-term, and evolving global research initiative investigating cardiovascular risk reduction 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, 'Lipoproteins and apolipoproteins', '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:
ASTEROID (A Study To Evaluate Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden)
- 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.
- Monday 29th September, 13.00-15.00.
ORION (Outcome of Rosuvastatin treatment on carotid artery atheroma: a Magnetic Resonance Imaging ObservatioN)
- Chu B, Hatsukami T, Polissar N et al. Use of magnetic resonance imaging to assess carotid atherosclerotic lesion distribution. On behalf of the ORION Study Group. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Chu B, Hatsukami T, Zhao X et al Evaluation of the reproducibility of carotid atherosclerotic lesion type determination using high-resolution magnetic resonance imaging. On behalf of the ORION Study Group. 13th International Symposium on Atherosclerosis. Kyoto, Japan, 2003.
- Wednesday 1st October, 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. 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.
2. 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.
3. 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.
4. 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.
5. 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). JAMA 2001;285:2486-97.
6. De Backer G, Ambrosioni E, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice. Executive summary of the third joint task force. European Heart Journal 2003;24:1601-10.
7. Sniderman AD, Fuberg CD, Keech et al. Apolipoproteins versus lipids as indices of coronary risk and as target for statin treatment. Lancet 2003;361:777-80.
8. Walldius G, Junger I, Holme I et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 2001; 358:2026-33.
9. Garfangnini A, Devoto G, Rosseli P et al. Relationship between HDL-cholesterol and apolipoprotein A-I and the severity of coronary artery disease. European Heart Journal 1995;16:465-70.
10. Francis MC, Frohlich JJ. Coronary artery disease in patients at low risk: apolipoprotein AI as an independent risk factor.
Atherosclerosis 2001;155:165-70.
11. Gotto AM, Whitney E, Stein EA et al. Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 2000;101:477-84.
12. Pedersen TR, Olsson AG, Faegerman O et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 1998;97:1453-60.
13. Ballantyne CM, Hoogeveen RC. Role of lipid and lipoprotein profiles in risk assessment and therapy. American Heart Journal 2003;146:227-33.
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.
STELLAR: Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin
MERCURY I: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY
CRESTOR and GALAXY Programme are trade marks of the AstraZeneca group of companies
For more information please see www.AstraZenecaPressOffice.com