New Analysis of the Meteor Study Demonstrate th...

ORLANDO, Florida, November 7 /PRNewswire/ --

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



    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 
equals 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.



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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.



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