METEOR Trial Shows CRESTOR Slowed Progression Of Atherosclerosis In People At Low-Risk* Of Coronary Heart Disease
LONDON, March 26, 2006-AstraZeneca today announced that the
METEOR clinical trial of CRESTOR is the first study to show a
positive effect on atherosclerosis in people with early signs of
carotid artery disease and at low risk of coronary heart disease
The study, using CRESTORTM (rosuvastatin) 40mg and presented at 56th Scientific Sessions of the American College of Cardiology, resulted in subjects showing a significantly slower rate of progression of atherosclerosis when compared to placebo. When assessed vs. baseline, no significant progression was observed in the 40 mg rosuvastatin arm over the two-year duration of the study, while significant progression vs. baseline was observed in the placebo arm.
The data demonstrated that the CRESTOR 40mg patients, with moderately increased LDL (‘bad’) cholesterol levels (mean 154 mg/dL) and no established atherosclerosis, experienced a 0.0014 mm/yr decrease in the mean maximum carotid intima-media thickness – a marker of atherosclerotic burden,compared to a progression of 0.0131 mm/yr for those on placebo (p<0.0001). CRESTOR 40 mg was well tolerated during the two years of the study.
With completion of this study, CRESTOR has now been studied across the atherosclerosis disease spectrum, first with ASTEROID, which included patients with established coronary artery disease and at a high risk of CHD events, and now with METEOR, which evaluated CRESTOR in asymptomatic subjects with early disease and at low CHD risk.
“It’s exciting to see that by using rosuvastatin we can potentially slow or even stop the disease progression in people with relatively modest atherosclerosis,” said lead investigator John R. Crouse, III, M.D., Professor of Medicine and Public Health Sciences and Associate Director of the Wake Forest University School of Medicine (WFUSM) General Clinical Research Centre. “METEOR provides evidence that the effect of rosuvastatin on dyslipidaemia translates into a beneficial effect on the progression of atherosclerosis.”
Atherosclerosis occurs when there is a build-up of fatty or fibrous deposits, to form areas called plaques, in the artery wall. The build-up of plaques causes the artery to narrow and this can reduce the blood supply to vital organs such as the heart and brain, resulting in symptoms such as angina or transient ischaemic attacks. Plaques can also rupture leading to thrombus formation, which can result in a sudden, complete blockage of blood flow. In the heart, this causes a heart attack, and in the brain, this causes a stroke. Atherosclerosis is a progressive disease and the main cause of cardiovascular disease – the number one killer worldwide.
A recently published independent post hoc analysis combining data from four prospective trials, including ASTEROID, showed that by substantially both decreasing LDL-C and increasing HDL-C by more than 7.5 percent, a beneficial effect on atherosclerosis can be achieved. In METEOR, CRESTOR was associated with a 48.8 percent reduction in LDL-C and an 8.0 percent increase in HDL-C (both p<0.0001 vs placebo). These results are consistent with the above finding and provide additional confirmation that the lowering of LDL-C and raising of HDL-C offered by CRESTOR translate into beneficial effects on atherosclerosis.
METEOR (Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin) was a 24-month, randomised, double-blind, placebo-controlled, international study to evaluate the effect of CRESTOR 40mg in 984 asymptomatic, hypercholesterolaemic patients with a low risk of coronary heart disease (Framingham ten year risk <10 percent ) and evidence of sub-clinical atherosclerotic disease as determined by a thickened carotid artery wall (maximum intima media thickness (IMT) >1.2 and <3.5 mm). METEOR used B-mode ultrasound imaging to assess and measure change in mean maximum IMT of 12 vessel sites in the carotid artery. The study evaluated low risk subjects not indicated for statin therapy to permit inclusion of a comparative placebo arm.
Currently, CRESTOR is indicated for the treatment of lipid disorders. The results from the METEOR study, supported by data from the ASTEROID study and including the ORION trial, formed the basis of the atherosclerosis regulatory submissions filed in the European Union and the United States in January 2007. These submissions seek to expand the use of CRESTOR to include the treatment of atherosclerosis with the purpose of impacting the progression of the disease in patients in whom lipid-lowering therapy is indicated.
These new results from METEOR add to the wealth of CRESTOR efficacy data from its extensive GALAXY clinical trials programme, designed to address important unanswered questions in statin research and to investigate the impact of CRESTOR on cardiovascular risk reduction and patient outcomes. Currently, more than 63,000 patients have been recruited from 55 countries worldwide to participate in the GALAXY Programme.
CRESTOR has now received regulatory approvals in over 90 countries across five continents. Over 9 million patients have been prescribed CRESTOR worldwide. Data from clinical trials and marketed use shows that the safety profile for CRESTOR is in line with other marketed statins. Annual sales for Crestor exceeded $2 billion for the first time in 2006.
The 40 mg dose is the highest registered dose of CRESTOR. CRESTOR should be used according to the prescribing information, which contains recommendations for initiating and titrating therapy according to the individual patient profile. In most countries, the usual recommended starting dose of CRESTOR is 10mg. The 40mg dose should only be used in patients who have not ac hieved their LDL-C goal utilizing the 20mg dose of CRESTOR.
25 March 2007
Edel McCaffrey, Tel: +44 (0) 207 304 5034
Steve Brown, Tel: +44 (0) 207 304 5033
Mina Blair, Tel: +44 (0) 207 304 5084
Jonathan Hunt, Tel: +44 (0) 207 304 5087
Jörgen Winroth, Tel: +1 (212) 579 0506
Ed Seage, Tel: +1 302 886 4065
Notes To Editors
* People at low-risk of coronary heart disease as described in the METEOR study had a Framingham 10- year risk of less than 10 percent. The Framingham risk score is a method to determine an individual's risk of having either a fatal or non-fatal heart attack over the following 10 years. The risk score is based on an
individual's cholesterol level, blood pressure, smoking status, age and gender.
ASTEROID (A Study To Evaluate the Effect of Rosuvastatin On
Intravascular Ultrasound-Derived Coronary Atheroma Burden) was a
104-week, open label, single-arm, blinded endpoint study designed
to study the effect of CRESTOR 40mg in 507 patients who had
undergone coronary angiography and who had evidence of coronary
artery disease (CAD).
Key findings from ASTEROID include:
CRESTOR brought about a 0.79 per cent (median) reduction in
percent atheroma volume in the entire target vessel (p<0.001)
– first primary endpoint
CRESTOR brought about a 9.1 per cent (median) reduction in total atheroma volume in the most diseased 10mm segment of the target vessel (p<0.001) – second primary endpoint
CRESTOR brought about a 6.8 per cent (median) reduction in total atheroma volume in the entire target vessel (p<0.001) – secondary endpoint
These changes were associated with a 53 per cent reduction in LDL-C (p<0.001) and a 15% increase in HDL-C (p<0.001)
ORION (Outcome of Rosuvastatin Treatment on Carotid Artery Atheroma: a Magnetic Resonance Imaging ObservatioN) was the first study to use advanced, high resolution MRI to investigate the effect of a statin – CRESTOR - on the change in the composition of plaques in the carotid artery wall. Forty-three (43) patients with moderate hypercholesterolemia and established carotid atherosclerosis were treated with either CRESTOR low dose (5 mg) or high dose (40/80 mg) for two years.