First Study To Show Positive Benefit On Atherosclerosis For People With Early Signs Of Diseased Arteries

First Study To Show Positive Benefit On Atherosclerosis For People With Early
Signs Of Diseased Arteries

METEOR Trial Shows CRESTOR Slowed Progression Of Atherosclerosis In People At
Low-Risk* Of Coronary Heart Disease

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 (CHD).


 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 achieved their
LDL-C goal utilizing the 20mg dose of CRESTOR.

For further information please visit www.astrazeneca.com 

Media enquiries: 
Staffan Ternby, Tel: 08-553 261 07, 070-557 43 00
Edel McCaffrey, Tel: +44 (0) 207 304 5034
Steve Brown, Tel: +44 (0) 207 304 5033

Investor Relations: 
Mina Blair, Tel: +44 (0) 207 304 5084
Jonathan Hunt, Tel: +44 (0) 207 304 5087
Staffan Ternby, Tel: 08-553 261 07, 070-557 43 00
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
Ø 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
Ø 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
Ø CRESTOR brought about a 6.8 per cent (median) reduction in total atheroma
volume in the entire target vessel (p<0.001) - secondary endpoint
Ø 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.