New Study Suggests Rosuvastatin is Associated With Arresting the Progression of Atherosclerosis

Main Category: Cholesterol
Article Date: 26 Apr 2005 - 12:00 PST

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Results from ORION indicate that significant lowering of bad cholesterol levels (>50%) are also associated with regressing plaques at sites with the most disease London, United Kingdom, 24 April 2005.

The ORION study, presented today at an international meeting of cardiology specialists,* is the first study to examine and visualise the effect of the statin treatment, rosuvastatin (CRESTORTM ), on the composition of plaques in the carotid arteries in the neck by obtaining detailed pictures using an advanced, non-invasive imaging technique called magnetic resonance imaging (MRI).1,2

Findings from this preliminary study, in 35 patients with cardiovascular disease, suggest substantial reductions of bad cholesterol (LDL-cholesterol or LDL-C) with rosuvastatin are associated with arrested progression in the size of carotid artery plaques and improving the composition of the most diseased sites in the artery wall by reducing the percentage of fatty material (lipid) within the plaque's core.2

Professor Hatsukami, principal investigator of the ORION study, comments "Plaques with larger lipid cores are believed by medical experts to be at higher risk of rupture, which can lead to sudden cardiovascular events, such as heart attack or stroke, often without any prior symptoms.3 So, treatment that tries to stabilise plaques, for example by reducing the size of the lipid core, may become a vital way of reducing the risk of cardiovascular events."

Atherosclerosis is a progressive disease and the main cause of cardiovascular disease - the number one killer worldwide.4,5 It is estimated that atherosclerosis accounts for more than 70% of all deaths from cardiovascular disease in the US.6 Atherosclerosis is caused by the build-up of plaques (fatty or fibrous deposits) in the artery walls. This can result in the narrowing of the arteries, which can reduce the supply of blood to vital organs such as the heart and brain. Plaques can also rupture, leading to a sudden, complete blockage of blood flow. Narrowing of the arteries or rupturing of plaques can cause a heart attack or stroke. The ORION study specifically examined the carotid arteries, which are found in the neck and provide oxygenated blood to the brain.

Rosuvastatin (CRESTOR TM ) 10-40mg

In the majority of countries where rosuvastatin is approved, the 10, 20 and 40mg doses are available:

All patients should be started on rosuvastatin 10mg, including those who have never been on a statin before and patients who are switched over from any dose of any other statin. The majority of patients achieve their LDL-C goal with rosuvastatin 10mg.

If necessary, dose adjustment to rosuvastatin 20mg can be made. Patients with severe hypercholesterolaemia and at high cardiovascular risk who do not achieve their LDL-C goal with rosuvastatin 20mg may be titrated to the maximum dose of rosuvastatin 40mg.

Rosuvastatin should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include renal impairment; hypothyroidism; personal or family history of hereditary muscular disorders; previous history of muscular toxicity with another statin or fibrate; alcohol abuse; age >70 years; situations where an increase in plasma levels may occur; concomitant use of fibrates.

However, please note that prescribing information may differ between countries. Therefore, doctors should always consult their local prescribing information before using CRESTOR.

Rosuvastatin has now received regulatory approvals in 73 countries across five continents and has been launched in over 58 countries worldwide, including 19 European markets, the US and Canada. Over 4.5 million patients have been prescribed rosuvastatin and 19 million prescriptions have been written worldwide. The post-marketing experience supports the favourable benefit:risk profile of rosuvastatin. Rosuvastatin 10mg is the usual recommended start dose for patients new to statin treatment and also for those switching to rosuvastatin 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 world's leading pharmaceutical companies with healthcare sales of over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

Rachael Wood, Global PR Manager, Cardiovascular Therapy Area, AstraZeneca
Tel: +44 (0) 1625 519514
Mobile: +44 (0) 7980 669242
Email: rachael.wood@astrazeneca.com

Notes to editors:

* The European Atherosclerosis Society (EAS) Congress is organised by the European Atherosclerosis Society, which is devoted to advancing knowledge of the causes, natural history, treatment and prevention of atherosclerosis. One major activity of the European Atherosclerosis Society is the organisation of their annual congress, which is taking place this year in Prague, Czech Republic from 23 April to 26 April 2005.

The importance and advantages of magnetic resonance imaging (MRI) techniques

There are several techniques available for the study of atherosclerosis and the level of detail required largely dictates the technique used. Advanced, non-invasive MRI is a valuable tool not only for the detection of atherosclerosis, but also for studying the size, shape and composition of atherosclerotic plaques, the effects on blood flow and treatment. By using this technique, valuable insights into the effect of treatment oatherosclerosis can be obtained.

Atherosclerosis

The main cause of cardiovascular disease (CVD) is atherosclerosis (a general term for the narrowing and hardening of the arteries).4

The World Health Organization (WHO) reports that CVD is the world's number one killer and accounts for approximately one in three of all deaths5

It has been estimated that there is one death from CVD every two seconds, one heart attack every five seconds and one stroke every six seconds5

Over 70% of CVD deaths in the US are related to atherosclerosis 6

Atherosclerotic cerebrovascular disease is the third leading cause of death and the leading cause of major disability amongst adults in the US.6

In westernised societies, atherosclerosis is the underlying cause of 50% of all deaths.4

ORION Results

In ORION, 35 patients with cardiovascular disease were treated with either rosuvastatin 5mg or 40mg for two years and the end results compared to the start of the study show:1

Rosuvastatin 5mg and 40mg significantly lower bad cholesterol (LDL-C) by 39% and 58%, respectively (p<0.001 from baseline and 40mg rosuvastatin versus 5mg rosuvastatin)

Rosuvastatin is associated with arresting the progression of carotid atherosclerosis as 5mg and 40mg result in no significant median (mean) change in carotid artery wall volume: 0.5% (-1.2%) and -1.4% (1.1%), respectively (p=NS). i.e. there was no significant increase in carotid artery wall volume over the two year course of the study

Where regression of carotid atherosclerosis was shown, this was associated with more intensive LDL-C lowering as patients whose artery wall volume regressed had a mean LDL-C reduction of 56% and achieved a mean LDL-C level of 69 mg/dL

At the most diseased sites within plaques, the percentage of the plaque occupied by the lipid core (% lipid core) was reduced by 17.6% in the 5mg group (p=NS) and by 35.5% in the 40mg group (p=0.006) after two years of treatment. 75% and 90% of these plaques demonstrated a decrease in the % lipid core with rosuvastatin 5mg and 40mg, respectively

In patients who did not have a lipid core in their plaques at the start of the study, none developed a lipid core over the two year study duration of treatment with rosuvastatin 5mg or 40mg

No significant difference was observed between rosuvastatin 5mg and 40mg for the atherosclerosis endpoints

Both rosuvastatin 5mg and 40mg were well tolerated.

Other rosuvastatin studies at EAS

The results from ORION suggest that intensive reductions (>50%) in LDL-C have a beneficial effect on the composition of atherosclerotic plaques. Numerous studies have consistently shown rosuvastatin to be the most effective statin at lowering LDL-C.7-20 The benefits provided to patients by rosuvastatin were further confirmed by the first results from the PULSAR21 study, also presented at EAS. This study highlights that the rosuvastatin 10 mg dose is more effective than double the dose of another statin, atorvastatin 20mg. Additionally, this study showed that using rosuvastatin ensures significantly more patients reach the right levels of LDL-C recommended in European and US treatment guidelines. Rosuvastatin was also well tolerated in this study.

The rosuvastatin GALAXY Programme™

METEOR22 and ASTEROID23 are ongoing studies in the AstraZeneca GALAXY Programme™ which are evaluating the effects of rosuvastatin on atherosclerosis. Baseline patient characteristic data from METEOR has also been presented as a late breaking poster at this year's EAS congress.

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 rosuvastatin.

References

1. Chu B, Hatsukami TS, Polissar NL, et al. Determination of carotid artery atherosclerosis lesion type and distribution in hypercholesterolemic patients with moderate carotid stenosis using noninvasive magnetic resonance imaging. Stroke 2004;35:2444-448.

2. Hatsukami TS, Saam T, Yuyan C, et al. Rosuvastatin treatment arrests the progression of carotid atherosclerosis in moderately hypercholesterolaemic subjects: a high-resolution magnetic resonance imaging trial. 75th European Atherosclerosis Society Congress, Prague, Czech Republic 2005.

3. Maseri A, Fuster V. Is there a vulnerable plaque? Circulation 2003;107:2068-71.

4. Lusis AJ. Atherosclerosis. Nature 2000;407:233-41.

5. World Health Report 2004. World Health Organization. http://www.who.int.

6. National Center for Health Statistics. http://www.cdc.gov/nchs/hus.htm

7. Blasetto JW, Stein EA, Brown WV, et al. Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. American Journal of Cardiology 2003;91 (suppl):3C-10C.

8. Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). American Journal of Cardiology 2003;92:152-60.

9. Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals: measuring effective reductions in cholesterol using rosuvastatin therapy (MERCURY I) study. American Heart Journal 2004;147:705-12.

10. Franken A, Wolffenbuttel B, Vincent J. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with Type 2 diabetes. Atherosclerosis Supplements 2004; 5(1):118, Abs M.513.

11. Jukema J, Liem A, Dunselman P, et al. LDL/HDL-C ratio in patients with coronary artery disease and low HDL-C: the RADAR study. Atherosclerosis Supplements 2004;5:125, Abs M.542.

12. Berne C, Siewert-Delle A. Use of rosuvastatin versus atorvastatin in Type 2 diabetes mellitus subjects. Atherosclerosis Supplements 2004;5(1):107, Abs M.463.

13. Betteridge DJ, Gibson M. Effect of rosuvastatin and atorvastatin on LDL-C and CRP levels in patients with Type 2 diabetes; results of the ANDROMEDA study. Atherosclerosis Supplements 2004;5(1):107-8 Abs M.464.

14. Davidson M, Ma P, Stein EA, et al. Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb
hypercholesterolemia. American Journal of Cardiology 2002;89:268-75.

15. Schwartz GG, Bolognese MA, Tremblay BP, et al. Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomised, controlled trial. American Heart Journal 2004;148:e4, H1-H9. 16. Olsson AG, Istaad H, Luurilla O, et al. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolaemia. American Heart Journal 2002;144:1044-51.

17. Schneck DW, Knopp RH, Ballantyne CM, et al. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. American Journal of Cardiology 2003;91:33-41.

18. Stein E, Strutt KL, Miller E, Southworth H. Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. American Journal of Cardiology 2003;92:1287-93

19. Paoletti R, Fahmy M, Mahla G, et al. Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: A randomized, double-blind study. Journal of Cardiovascular Risk 2001;8:383-90.

20. Brown W, Bays HE, Hassman DR, et al. Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: A randomized, double-blind, 52-week trial. American Heart Journal 2002;144:1036-43.

21. Clearfield M, Kallend D, Palmer M for the PULSAR study investigators. Efficacy and safety of rosuvastatin 10mg versus atorvastatin 20mg: Results of the PULSAR study. 75th European Atherosclerosis Society Congress, Prague, Czech Republic 2005.

22. Crouse III JR, Grobbee DE, O'Leary DH, et al. Measuring effects on intima media thickness: An evaluation of rosuvastatin in subclinical atherosclerosis - the rationale and methodology of the METEOR Study. Cardiovascular Drugs & Therapy 2004;18:231-38.

Nissen S. Design and methodology of a study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived coronary atheroma burden: The ASTEROID study. Atherosclerosis Supplements 2003;4:27. Abs 1P-0037.

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