New Analysis of the METEOR Study Demonstrate the Positive Effects of CRESTOR(TM) on Atherosclerosis in Patients With two or More Risk Factors

New Analysis of the METEOR Study Demonstrate the Positive Effects of CRESTOR(TM) on Atherosclerosis in Patients With two or More Risk Factors

November 08, 2007

- Data Presented at AHA Scientific Sessions Adds to Body of
Evidence Highlighting Unique Benefits of CRESTOR Across the
Spectrum of Atherosclerosis Disease Progression

    ORLANDO, Fla., Nov. 7 /Xinhua-PRNewswire/ -- New
analysis of the METEOR (Measuring Effects on intima media
Thickness: an Evaluation Of Rosuvastatin) trial presented
today showed CRESTOR(TM) (rosuvastatin) 40mg slowed the
progression of carotid intima-media thickness (CIMT) in
patients at varying levels of risk for cardiovascular
disease while all placebo treated subjects exhibited
significantly higher progression rates.

    This new analysis was conducted in subjects defined by
the Framingham risk assessment tool as having less than two
or two or more risk factors (RF) with either thinner or
thicker CIMT (<1.749 mm [median] vs. more 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 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 Endocrinology
at Wake Forest University School of Medicine, Winston-Salem,
NC.

    The analysis showed that CRESTOR, when compared with
placebo, slows progression of carotid atherosclerosis in
subjects at relatively low risk of cardiovascular disease
(<2RF + Thinner CIMT; 0.0007mm/yr v. 0.0123mm/yr with
placebo and <2RF + Thicker CIMT; -0.0012mm/yr v.
0.0116mm/yr with placebo). Furthermore, those with more
risk factors 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; -0.0013mm/yr v. 0.0144mm/yr with placebo and 2+RF +
Thicker CIMT; -0.0071mm/yr v. 0.015mm/yr with placebo).

    A further analysis presented earlier at AHA Scientific
Sessions demonstrated CRESTOR significantly 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. Data showed
that aggressive LDL-C lowering with CRESTOR exerts a
beneficial effect on atherosclerosis during the first year
of treatment, which parallels the timing of event rate
reduction seen in clinical trials. 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 between
        CRESTOR and placebo increased: -0.0009 mm/yr and
0.0131 mm/yr,
        respectively (p<0.0001).

     -- After 24 months, 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.

    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
ischaemic 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 number one
killer worldwide.(1)

    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 40 mg in 984 asymptomatic,
hypercholesterolaemic patients with a low risk of CHD
(Framingham ten-year risk <10%) and evidence of
sub-clinical atherosclerotic disease as determined by a
thickened carotid artery wall (maximum CIMT >1.2 and
<3.5 mm). METEOR data presented earlier this year were
the first to show a positive effect on atherosclerosis in
this patient population.

    CRESTOR is indicated for the treatment of lipid
disorders. The results from the METEOR study, supported by
data from the ASTEROID(2) and ORION trials, formed the
basis of the atherosclerosis regulatory submissions filed
in the European Union and the United States in January
2007. The CRESTOR (rosuvastatin) Prescribing Information in
Europe was updated to incorporate data from the METEOR study
in section 5.1 of the SmPC in July 2007.

    These new results from METEOR add to the wealth of
CRESTOR efficacy data from its extensive GALAXY clinical
trials programme(3), designed to address important
unanswered questions in statin research. Currently, more
than 69,000 patients have been recruited in over 55
countries worldwide to participate in the GALAXY
Programme.
    CRESTOR has now received regulatory approvals in over
90 countries. More than 11 million patients have been
prescribed CRESTOR worldwide. Data from clinical trials(4)
and real world use(5, 6) shows that the safety profile for
CRESTOR is in line with other marketed statins.
    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 individual
patient profiles. In most countries, the usual recommended
starting dose of CRESTOR is 10 mg. The 40 mg dose should
only be used in patients who have not achieved their LDL-C
goal with the 20 mg dose of CRESTOR.

    Notes to Editors:

    (i) 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 40 mg 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% (median) reduction in
percent atheroma
        volume in the entire target vessel (p<0.001) -
first primary endpoint

     -- CRESTOR brought about a 9.1% (median) reduction in
total atheroma
        volume in the most diseased 10 mm segment of the
target vessel
        (p<0.001) - second primary endpoint

     -- CRESTOR brought about a 6.8% (median) reduction in
total atheroma
        volume in the entire target vessel (p<0.001) -
secondary endpoint

     -- These changes were associated with a 53% reduction
in LDL-C (p<0.001)
        and a 15% increase in HDL-C (p<0.001)

    (ii) 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.

    About AstraZeneca

    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
US$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 FTSE4 Good Index. For more information about
AstraZeneca, please visit: http://www.astrazeneca.com

    This press release has been made available on worldwide
press communication media for the benefit of correspondents
writing for the medical professional press. Differing
national legislation, codes of practice, medical practice
etc mean that you should contact your local AZ press office
to obtain information designed for use in your country. In
particular this press release has not been prepared for use
in the USA.

    References

    (1) Bonow, R, Smaha, L, Smith, S et al. The
International Burden of Cardiovascular Disease: Responding
to the Emerging Global Epidemic. Circulation 2002;106:1602

    (2) Nissen SE, Nicholls SJ, Sipahi I et al. Effect of
very high-intensity statin therapy on regression of
coronary atherosclerosis: the ASTEROID trial. JAMA 2006
295:1556-65

    (3) Schuster H. The GALAXY Program: an update on
studies investigating efficacy and tolerability of
rosuvastatin for reducing cardiovascular risk. Expert Rev
Cardiovasc Ther. 2007 5:177-93.

    (4) Shepherd J, Hunninghake DB, Stein EA et al. Safety
of rosuvastatin. Am J Cardiol. 2004 94:882-8

    (5) McAfee AT, Ming EE, Seeger JD et al. The
comparative safety of rosuvastatin: a retrospective matched
cohort study in over 48,000 initiators of statin therapy.
Pharmacoepidemiol Drug Saf. 2006 15:444-53

    (6) Goettsch WG, Heintjes EM, Kastelein JJ et al.
Results from a rosuvastatin historical cohort study in more
than 45,000 Dutch statin users, a PHARMO study.
Pharmacoepidemiol Drug Saf. 2006 15:435-43.

    For further information please visit:
http://www.AstraZenecaPressOffice.com 


    For more information, please contact:

     Ben Strutt
     Global PR Manager
     Cardiovascular Therapy Area
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]