Healthcare Industry News: rosuvastatin
News Release - November 7, 2007
New Analysis of METEOR Study Demonstrate Effects of AstraZeneca's CRESTOR(R) (Rosuvastatin Calcium) on Atherosclerosis in Patients With Two or More Risk Factors for Cardiovascular DiseaseORLANDO, Fla., Nov. 7 (HSMN NewsFeed) -- A new analysis presented today from METEOR (Measuring Effects on intima media Thickness: an Evaluation Of rosuvastatin) showed CRESTORŽ (rosuvastatin calcium) 40 mg slowed the progression of carotid intima-media thickness (CIMT) in four patient populations at varying levels of risk for cardiovascular disease. The sub- study was conducted in subjects defined by the Framingham risk assessment tool as having less than two or two or more risk factors (RF) and either thinner or thicker CIMT (<1.749 mm [median] vs. Greater Than or Equal To 1.749 mm). Results demonstrated that CRESTOR significantly slowed the progression of CIMT in all four subgroups (all p<0.02), compared to placebo treated subjects who all exhibited significantly higher progression rates. These data were presented at the American Heart Association Scientific Sessions in Orlando, Florida.
The new analysis showed that CRESTOR, when compared with placebo, slows progression of carotid atherosclerosis in subjects at relatively low risk for cardiovascular disease (<2RF + Thinner CIMT; 0.0007 mm/yr v. 0.0123 mm/yr with placebo and <2RF + Thicker CIMT; -0.0012 mm/yr v. 0.0116 mm/yr with placebo). Furthermore, those with more RFs and those with greater baseline thickness in the CRESTOR-treated group exhibited a greater trend toward regression or a greater negative slope (2+RF + Thinner CIMT; -0.0013 mm/yr v. 0.0144 mm/yr with placebo and 2+RF + Thicker CIMT; -0.0071 mm/yr v. 0.015 mm/yr with placebo).
"The METEOR trial continues to provide important information regarding the effects of CRESTOR on atherosclerotic progression in subjects with various degrees of risk based on conventional risk factors and carotid artery wall thickness," said John R. Crouse, III, M.D., lead investigator and Professor of Medicine at Wake Forest University School of Medicine, Winston-Salem, NC.
Atherosclerosis is a progressive disease that typically begins in early adulthood and progresses as people grow older. Those with risk factors for coronary heart disease, such as those included in the Framingham risk assessment tool, have an increased risk of atherosclerosis. These risk factors include age, high LDL cholesterol, low HDL cholesterol, high blood pressure, and smoking. Earlier this year, METEOR demonstrated that CRESTOR significantly slowed progression of atherosclerosis (http://www.astrazeneca.com/pressrelease/5317.aspx) in subjects with early signs of the disease and who are at low cardiovascular risk.(1)
A second analysis presented earlier at AHA Scientific Sessions demonstrated CRESTOR reduced CIMT progression after 12 months with a rate of 0.0032 mm/yr compared with 0.0133 mm/yr for placebo (p=0.049). This analysis evaluated the shortest time period at which differences in atherosclerosis progression rates were detectable after initiating CRESTOR therapy. Additional results include:
-- Differences in CIMT progression rates between the CRESTOR and placebo groups were apparent after six months: 0.0023 mm/yr and 0.0106 mm/yr, respectively (p=0.36).
-- After 18 months, the difference in CIMT progression rates increased: -0.0009 mm/yr and 0.0131 mm/yr, respectively (p<0.0001).
-- After 24 months, the difference in CIMT progression between the CRESTOR and placebo groups increased further; -0.0014 mm/yr and 0.0131 mm/yr, respectively (p<0.0001).
Ultrasound assessments were made at 12 carotid artery sites at baseline and every 6 months up to two years. In these analyses, the same statistical method was applied to the data cut at 6 months, 1 year, and 18 months, in addition to the analysis of all data at two years.(2)
METEOR (Measuring Effects on intima media Thickness: an Evaluation Of rosuvastatin) was a 24-month, randomized, double-blind, placebo-controlled, international study to evaluate the effect of CRESTOR 40 mg in 984 asymptomatic, hypercholesterolemic patients with a low risk for CHD (Framingham ten-year risk <10%) and evidence of sub-clinical atherosclerotic disease as determined by a thickened carotid artery wall (maximum CIMT Greater Than or Equal To 1.2 and <3.5 mm). METEOR is the only placebo controlled study to demonstrate a slowing of progression of atherosclerosis in subjects with early signs of the disease and at low cardiovascular risk.
The effects of CRESTOR on atherosclerosis have now been studied among different populations using three key techniques -- CIMT (METEOR), IVUS (ASTEROID), and MRI (ORION). These three studies formed the basis of AstraZeneca's application to the FDA for an update to the CRESTOR Prescribing Information.
METEOR, ASTEROID and ORION are part of AstraZeneca's GALAXY Program, a large, comprehensive, long-term and evolving global research initiative designed to address important unanswered questions in statin research and to investigate the impact of CRESTOR on cardiovascular risk reduction and patient outcomes. Another GALAXY trial, JUPITER, which is currently underway, is the first study of its kind designed to investigate the effects of a statin medication on the reduction of cardiovascular morbidity and mortality among 15,000 individuals with normal to low cholesterol levels and elevated C- reactive protein (CRP) levels. To date, the GALAXY Program has recruited more than 69,000 subjects in more than 55 countries around the world.
Atherosclerosis occurs when there is a build-up of fatty or fibrous deposits, known as plaques, in the artery wall. Plaques cause the artery to narrow, and can reduce the blood supply to the heart, brain, and other vital organs, resulting in symptoms such as angina or transient ischemic attacks. Plaques can also rupture and lead to the formation of a thrombus, which can result in a sudden, complete blockage of blood flow. In the heart, this blockage causes a heart attack; in the brain, it causes a stroke. Atherosclerosis is a progressive disease and the main cause of cardiovascular disease -- the No.1 killer worldwide.
CRESTOR is a once-daily prescription statin medication indicated for use as an adjunct to diet in the treatment of various lipid disorders including primary hypercholesterolemia, mixed dyslipidemia and isolated hypertriglyceridemia, available in a 5-, 10-, 20-, and 40-mg dose. CRESTOR has not been determined to prevent heart disease, heart attacks, or strokes. For patients with hypercholesterolemia and mixed dyslipidemia, the usual recommended starting dose of CRESTOR is 10 mg. However, initiation of therapy with 5 mg once daily should be considered for patients requiring less aggressive LDL-C reductions or who have predisposing factors for myopathy, and for special populations such as patients taking cyclosporine, Asian patients, and patients with severe renal insufficiency. For patients with marked hypercholesterolemia (LDL-C >190 mg/dL) and aggressive lipid targets, a 20-mg starting dose may be considered. AstraZeneca licensed worldwide rights to CRESTOR from the Japanese pharmaceutical company Shionogi & Co., Ltd. For more complete prescribing information, please visit: http://www.crestor.com.
Important Safety Information
CRESTOR is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases, in women who are pregnant or may become pregnant, and in nursing mothers. It is recommended that liver function tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with CRESTOR and with other drugs in this class. The 40-mg dose of CRESTOR is reserved only for those patients who have not achieved their LDL-C goal utilizing the 20-mg dose of CRESTOR once daily. When initiating statin therapy or switching from another statin therapy, the appropriate CRESTOR starting dose should first be utilized, and only then titrated according to the patient's individualized goal of therapy. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of this combination. Combination therapy with rosuvastatin and gemfibrozil should generally be avoided. CRESTOR should be prescribed with caution in patients with predisposing factors for myopathy, such as renal impairment, advanced age, and inadequately treated hypothyroidism. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. CRESTOR is generally well-tolerated. Adverse reactions have usually been mild and transient. The most frequent adverse events thought to be related to CRESTOR were myalgia (3.3%), constipation (1.4%), asthenia (1.3%), abdominal pain (1.3%) and nausea (1.3%).
AstraZeneca (NYSE: AZN ) 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 $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
In the United States, AstraZeneca is a $12.44 billion healthcare business with more than 12,000 employees. For nearly three decades, AstraZeneca has offered drug assistance programs side by side with its medicines, and over the past five years, has provided over $3 billion in savings to more than 1 million patients throughout the US and Puerto Rico. AstraZeneca has been named one of the "100 Best Companies for Working Mothers" by Working Mother magazine and is the only large pharmaceutical company named to FORTUNE magazine's 2007 list of "100 Best Companies to Work For." In 2006, for the fifth consecutive year, Science magazine named AstraZeneca a "Top Employer" on its ranking of the world's most respected biopharmaceutical employers.
For more information about AstraZeneca, please visit: http://www.astrazeneca-us.com.
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(1) Reference Original METEOR Abstract from ACC
(2) Reference METEOR Abstract 1
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