
April 2004
1st data show CRESTOR highly effective at lowering LDL-C in patients with type 2 diabetesResults from three new studies are first to confirm superiority of CRESTORTM compared with atorvastatin in patients with type 2 diabetes and dyslipidaemiaSeville, Spain, Sunday 18 April 2004. New data show CRESTORTM (rosuvastatin) provides superior reductions in a major cardiovascular risk factor, LDL-cholesterol (LDL-C), in patients with type 2 diabetes and dyslipidaemia compared to atorvastatin.1-3 Results from the CORALL study demonstrated that for each dose of CRESTOR, LDL-C was reduced significantly more than with double the dose of atorvastatin; LDL-C was reduced by 46%, 51% and 54% with CRESTOR 10mg, 20mg and 40mg respectively compared to 41%, 46% and 48% with atorvastatin 20mg, 40mg and 80mg, respectively (all p<0.05).1 CORALL is one of three new studies with CRESTOR presented at the European Atherosclerosis Society (EAS) Congress in this patient population.1-3
People with type 2 diabetes are three times more likely to die from a cardiovascular event than non-diabetics with the same cholesterol level and up to 80% die of cardiovascular disease.4 Reducing high levels of LDL-C is recognised as one of the primary treatment targets for type 2 diabetics5, 6 and lowering LDL-C with statin treatment has been demonstrated to be effective in reducing cardiovascular events in these patients.7-10 The latest US and European guidelines now set the low and challenging LDL-C goal of <2.5 mmol/L (100mg/dL) for these high risk patients.5, 6 A growing body of evidence suggests that additional prevention of major cardiovascular events may be achieved through lowering LDL-C levels below what was previously accepted as sufficient. A recent study has confirmed that a statin providing more effective reductions in LDL-C (by 42%) leads to greater protection against death or major cardiovascular events than standard statin treatment.11
Results presented today from the ANDROMEDA study show that low doses of CRESTOR reduced LDL-C by at least 50% and got more than 90% of patients with type 2 diabetes and dyslipidaemia to their new European LDL-C goal of <2.5 mmol/L.2 Also in this study, CRESTOR 10mg and 20mg reduced LDL-C by 51% and 57% respectively, significantly more than with atorvastatin 10mg and 20mg (39% and 46%, p<0.001 respectively) and as a result, significantly more patients treated with CRESTOR 10mg and 20mg (94% and 96% respectively) achieved their LDL-C goal than those treated with atorvastatin 10mg and 20mg (79%, p<0.001 and 87%, p=0.002 respectively).2 The superiority of CRESTOR was also confirmed in the CORALL study when at 18 weeks, 90% of patients on CRESTOR 40mg achieved this LDL-C goal compared to 78% on atorvastatin 80mg (p<0.05).1
Commenting on the results, lead investigator of the ANDROMEDA study Professor John Betteridge, Department of Medicine, The Middlesex Hospital, London,explains, "There are millions of people living with type 2 diabetes and raised cholesterol who are at a very high risk of suffering from a life-threatening cardiovascular event, such as heart attack or stroke. We know that statins reduce cardiovascular mortality in patients with raised LDL-cholesterol, and these important results show that CRESTOR offers an important and highly effective treatment option for patients with type 2 diabetes, bringing their LDL-cholesterol down to the recommended levels."
The benefits of CRESTOR on additional cardiovascular risk factors including the inflammatory marker, C-reactive protein (CRP), and other atherogenic lipid parameters were also reported.1-3 High levels of CRP are a strong predictor of cardiovascular events.12-14 CRESTOR 10mg and 20mg reduced CRP by 34% and 40% respectively, compared with 21% and 34% for atorvastatin 10mg and 20mg, respectively.2 In patients with type 2 diabetes and dyslipidaemia, CRESTOR also improved other lipid parameters such as triglyceride levels, non-HDL-C and the ApoB/ApoA-I ratio. 1-3
The three studies presented at EAS which investigated the benefits of CRESTOR compared to atorvastatin in patients with type 2 diabetes and dyslipidaemia were � CORALL, an 18-week forced-titration study conducted in The Netherlands comparing CRESTOR 10-40mg with atorvastatin 20-80mg in 263 patients;1 ANDROMEDA, a 16-week UK study in 509 patients comparing CRESTOR 10-20mg with atorvastatin 10-20mg;2 and URANUS, a 16-week Swedish study in 469 patients comparing CRESTOR 10-40mg with atorvastatin 10-80mg.3 Together these studies confirm that in patients with type 2 diabetes and dyslipidaemia, CRESTOR improves the atherogenic lipid profile more favourably than atorvastatin and enables more patients to achieve European LDL-C goals.1-3
CRESTOR has now received regulatory approvals in more than 50 countries across five continents and has been launched in over 40 countries worldwide, including 13 European markets, the US and Canada. Over one million patients have been prescribed CRESTOR and more than two million prescriptions have been written worldwide. The post-marketing experience supports the favourable benefit:risk profile of CRESTOR and confirms that the safety profile is comparable to other currently marketed statins. CRESTOR 10mg is the usual recommended start dose for patients new to statin treatment and also for those switching to CRESTOR from other statins regardless of prior dose.
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 $18.8 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.
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For further information please visit: www.AstraZenecaPressOffice.com or contact:
Onsite: Rachael Wood, Global PR Manager, Cardiovascular Therapy Area, AstraZeneca Tel: +44 (0) 1625 519514 Mobile: +44 (0) 7980 669242 Email: [email protected] or Offsite: Ellie Goss, Shire Health International Tel: +44 (0) 207 471 1519 Mob: +44 (0) 7747 803217
Notes to Editors: - CORALL = COmpare the effect of Rosuvastatin with Atorvastatin on Apo B/Apo A-1 ratio in patients with Type 2 diabetes meLLitus and dyslipidaemia
- ANDROMEDA = A raNdomised, Double blind, double dummy, multicentre phase IIIb parallel group study to compare the efficacy and safety of Rosuvastatin (10 mg and 20 mg) and atOrvastatin (10 Mg and 20 mg) in subjEcts with type II DiAbetes mellitus
- URANUS = Use of Rosuvastatin versus Atrovastatin iN type 2 diabetes mellitUS subjects.
Type 2 Diabetes and Cardiovascular Disease Type 2 diabetes is by far the most common form of diabetes, accounting for approximately 90 percent of all diabetes cases worldwide.15
Studies have shown a link between diabetes and cardiovascular disease (CVD): - Diabetics are two to four times more likely to develop CVD than non-diabetics.16-18
- Up to 80% of people with type 2 diabetes die of CVD.19
- Two thirds of diabetics are unaware of the cardiovascular complications associated with diabetes.20
Type 2 diabetes is often referred to in association with the metabolic syndrome as many type 2 diabetics exhibit the cluster of risk factors characteristic of this syndrome. However, although diabetic adults often have many of the risk factors associated with CVD, such as dyslipidaemia and obesity, these alone do not account for the increased risk of developing CVD in diabetic patients: - Risk has been shown to be higher among diabetics than non-diabetics at every age and risk factor level.18
- For each risk factor present, the risk of cardiovascular death is approximately three times greater in people with diabetes in comparison to those without the condition.4
- Risk of myocardial infarction (MI) for diabetics with no history of MI is similar to that of non-diabetics who have had a MI event.21
C-reactive protein C-reactive protein (CRP) has emerged as a major predictor of long-term cardiovascular risk independent of lipid levels and other traditional risk factors. In a landmark eight-year long study of nearly 28,000 women, more than half of those who suffered a major cardiovascular event had LDL-C levels considered low by current treatment guidelines.12 However when CRP evaluation was added to the cholesterol screen, it was found that the majority of these high-risk individuals were identifiable many years before they had a first cardiovascular event.
JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin), which is part of the extensive GALAXYTM Programme, is investigating the impact of CRESTOR 20mg on the prevention of cardiovascular events in subjects with raised CRP but normal levels of LDL-C. This study, involving 15,000 people, is the first large-scale prospective study to investigate the use of statin therapy on cardiovascular events in this 'at risk' patient population.22
Cardiovascular Disease The term cardiovascular disease (CVD) refers to a wide range of disorders affecting the heart and blood vessels. CVD can be sub-divided into the following diseases: - coronary heart disease (CHD) (e.g. heart attacks and angina)
- cerebrovascular disease (e.g. strokes and transient ischaemic attacks)
- peripheral vascular disease (e.g intermittent claudication)
CVD is estimated to account for approximately a third of all deaths globally and is the leading cause of mortality in Europe and the US. Over 16.7 million deaths each year are due to CVD (more than 45,000 deaths every day, and almost 32 deaths each minute).23 In Europe, about half of all deaths from CVD are from CHD and nearly one-third are from stroke.24
CRESTOR data at EAS: Clinical data:
- Wolffenbuttel BHR, Franken AAM and Vincent JJ on behalf of the Dutch CORALL study group. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes.
- Betteridge DJ, Gibson M, on behalf of the ANDROMEDA study investigators. Effect of rosuvastatin and atorvastatin on LDL-C and CRP levels in patients with type 2 diabetes: results of the ANDROMEDA study.
- Berne C, Siewert-Delle A, on behalf of the URANUS study investigators. Use of Rosuvastatin versus Atorvastatin in type 2 diabetes mellitus subjects: results of the URANUS study.
- Jukema JW, Liem AH, Dunselman PHJM et al. LDL/HDL-C ratio in patients with coronary artery disease and low HDL-C: the RADAR study
- Barter PJ, Stender S, Morrell JM et al. Effects of switching statins on non-HDL-C in hypercholesterolaemic patients and achievement of ATP III combined LDL-C and non-HDL-C goals in patients with elevated triglycerides: MERCURY I Trial results
- Mabuchi H, Nohara A, Higashikata T et al. Rosuvastatin Produces Substantial Improvements in the Lipid Profile of Japanese Patients with Heterozygous Familial Hypercholesterolemia
Pre-clinical:
- Kiian I and Dumler I. Rosuvastatin regulates RhoA and uPA/uPAR systems required for migration of human vascular smooth muscle cells.
- Otto A, Fontaine D, Fontaine J, Berkenboom G. Long-term rosuvastatin treatment protects against nitrate-induced oxidative stress.
- Chong T, Naples M, Federico L et al. Effect of rosuvastatin on hepatic production of atherogenic lipoproteins in an animal model of insulin resistance and diabetic dyslipidemia.
- Peters H, Kron S, Wang Y et al. Rosuvastatin slows the progressive course of chronic anti-thy1-induced glomerulosclerosis of the rat.
References: 1. Wolffenbuttel BHR, Franken AAM, Vincent JJ, on behalf of the Dutch CORALL study group. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes. 74th European Atherosclerosis Society Congress in Seville, Spain, April 2004 2. Betteridge DJ, Gibson M, on behalf of the ANDROMEDA study investigators. Effect of rosuvastatin and atorvastatin on LDL-C and CRP levels in patients with type 2 diabetes: results of the ANDROMEDA study. 74th European Atherosclerosis Society Congress in Seville, Spain, April 2004 3. Berne C, Siewert-Delle A, on behalf of the URANUS study investigators. Use of Rosuvastatin versus Atorvastatin in type 2 diabetes mellitus subjects: results of the URANUS study. 74th European Atherosclerosis Society Congress in Seville, Spain, April 2004 4. Website of International Diabetes Federation. Facts & Figures. Did you know? 5. de Backer G, Ambrosioni E, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal 2003;24:1601-1610 6. 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). JAMA 2001;285(19):2486-2497 7. Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G et al. Cholesterol lowering with Simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care 1997;19:614-620 8. Goldberg RB, Mellies MJ, Sacks FM, Moye LA, Howard BV, Howard WJ et al. Cardiovascular events and their reduction with Pravastatin in diabetic and glucose intolerant myocardial infarction survivors with average cholesterol levels. Circulation 1998;19:2513-2519 9. Sever PS, Dahlof B, Poulter N, Wedel H, for the ASCOT Steering Committee and ASCOT Investigators. Anglo-Scandinavian Cardiac Outcomes Trial � Lipid-Lowering Arm (ASCOT-LLA): Results in the Subgroup of Patients with Diabetes. J Am Coll Cardiol (suppl): 529A. Abstract 882-1 10. Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005-2016 11. Cannon CP, Braunwald E, McCabe CH et al. Comparison of Intensive and Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Eng J Med 2004;350:15 (available on-line at www.NEJM.org) 12. Ridker PM, Rifai N, Rose L et al. Comparison of C-reactive protein and LDL-C in the prediction of cardiovascular events. N Eng J Med 2002;347:1557-1565 13. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003;107:363-369 14. Ridker PM, Rifai N, Clearfield M et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959-1965 15. World Health Organization. Fact Sheet No. 138. Revised April 2002 16. Garcia MJ et al. Morbidity and mortality in diabetics in the Framingham population. Diabetes 1974;23(2):105-111 17. Assmann G, Schulte H. The prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. American Heart Journal 1988;116:1713-1724 18. Stamler J et al. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-444 19. Kirpichnikov D, Sowers JR. Diabetes mellitus and diabetes-associated vascular disease. Trends in Endocrinology and Metabolism 2001;12:225-230 20. Health and Human Services, American diabetes association renew campaign to help people with diabetes know their cardiovascular risks. New ADA survey shows many know little about risks of heart disease, stroke. Health and Human Services Press Release, February 2002. 21. Haffner SM et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-234 22. Ridker PM. Rosuvastatin in the Primary Prevention of Cardiovascular Disease Among Patients with Low LDL Cholesterol and Elevated High Sensitivity C-Reactive Protein (hsCRP): Rationale and Design of the Jupiter Trial. Circulation 2003:108:2292-2297 23. World Health Report 2003. World Health Organization. http://www.who.int 24. European Cardiovascular Disease Statistics, 2000 Edition, British Heart Foundation. http://www.bhf.org.uk
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