A combination treatment regimen of CRESTOR(TM)
(rosuvastatin) 40 mg and ezetimibe 10 mg demonstrated a 46% reduction
in levels of C-reactive protein (CRP), a marker of inflammation and
risk factor for cardiovascular disease, in high-risk patients. In just
six weeks, the combination regimen also helped more than half (58%) of
patients achieve dual CRP/LDL-C goals.(1) These post-hoc analysis
findings from the EXPLORER(a) study will be presented for the first
time this week at the World Congress of Cardiology in Barcelona.
Previous EXPLORER results released at ISA in June showed high-risk
patients achieved an unprecedented 70% reduction in LDL-C using
CRESTOR combination therapy.(2)
"Physicians have long relied on blood cholesterol as a key
indicator of cardiovascular risk, but recent research suggests that
adding a CRP goal to existing LDL-C targets could potentially further
reduce the risk of cardiovascular outcomes," said lead investigator
Professor Christie Ballantyne, director of the Center for
Cardiovascular Disease Prevention at the Methodist DeBakey Heart
Center and professor at Baylor College of Medicine, Houston, USA.
"Although additional studies are still needed, EXPLORER suggests that
a treatment regimen using CRESTOR and ezetimibe can help patients not
only to achieve optimal cholesterol targets, but also to significantly
reduce their levels of CRP."
Previous clinical trials have demonstrated limited success in
achieving dual CRP/LDL-C goals(3), particularly for high-risk patients
in whom target levels are CRP <2 mg/L combined with LDL-C <100 mg/dL
or LDL-C <70 mg/dL (depending on risk category). The significant
reductions in both markers seen in the EXPLORER study provide a new
opportunity for high-risk patients to potentially reduce their
cardiovascular risks with combination therapy.
Inflammation of the blood vessels and arteries can lead to serious
complications such as heart attack and stroke(4), and high levels of
CRP can predict these risks years before they actually occur. The
first outcomes study to examine the effect of statins on
cardiovascular morbidity and mortality among individuals with normal
to low cholesterol levels and elevated CRP is currently under way. The
objective of the study, known as JUPITER (Justification for the Use of
statins in Primary prevention: an Intervention Trial Evaluating
Rosuvastatin), is to determine whether long-term treatment with
CRESTOR will reduce the risk for cardiovascular events in this patient
population. CRESTOR already has been shown to be the most effective
statin at reducing LDL-C,(5-24) enabling most patients with high
cholesterol to successfully achieve their guideline LDL-C goal.
Key findings from EXPLORER:(1,25)
-- Significantly more patients (58% vs. 24%) achieved dual
LDL-C/CRP goals of LDL-C <100 mg/dL or <70 mg/dL (depending on
risk category) and CRP <2 mg/L at six weeks with CRESTOR 40mg
and ezetimibe 10mg compared with CRESTOR monotherapy.
-- CRESTOR and ezetimibe reduced CRP levels by 46% compared with
just 29% with CRESTOR monotherapy.
-- CRESTOR and ezetimibe also reduced mean LDL-C by an
unprecedented 70%.
-- Significantly (p<0.001) more patients achieved their NCEP ATP
III LDL-C goal of <100 mg/dL (94% vs 79%) and their European
LDL-C goal (94% vs. 74%) at six weeks with CRESTOR and
ezetimibe compared with CRESTOR monotherapy.
-- Both CRESTOR monotherapy and CRESTOR combined with ezetimibe
produced similar increases in HDL-C ("good" cholesterol)
(8.5%vs. 10.8%).
-- CRESTOR and ezetimibe were both well tolerated.
The results from EXPLORER add to the outstanding 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 51,000 patients have been
recruited from 55 countries worldwide to participate in the GALAXY
Programme.
CRESTOR has now received regulatory approvals in more than 75
countries across five continents. Over seven million patients have
been prescribed CRESTOR worldwide, and from clinical trials, marketed
use, the recently published National Lipid Association safety
evaluation, and early pharmacoepidemiology data, the safety profile 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 the individual patient profile. In most countries, the
usual recommended starting dose of CRESTOR is 5 or 10mg.
For further information please visit:
www.AstraZenecaPressOffice.com.
Notes to Editors:
EXPLORER was a 12-week, randomised trial of 469 patients with
LDL-C 160-<250 mg/dL (4.1-<6.5 mmol/L) designed to evaluate whether
adding ezetimibe to CRESTOR would enable more patients with severely
high cholesterol to achieve guideline lipid goals compared with
CRESTOR monotherapy. Patients participated in a six-week dietary
lead-in followed by six weeks of randomised treatment with
rosuvastatin 40 mg alone or in combination with ezetimibe 10 mg.
References:
(a) EXPLORER (Examination of Potential Lipid modifying effects Of
Rosuvastatin in combination with Ezetimibe versus Rosuvastatin
alone)
1. Ballantyne C, Sosef F, Duffield E. Rosuvastatin Plus Ezetimibe
for Achievement of Low-Density Lipoprotein Cholesterol and
C-Reactive Protein Goals: Results From the EXPLORER Study.
Poster presented at: World Congress of Cardiology; 6
September, 2006; Barcelona, Spain.
2. Ballantyne C, Sosef F, Duffield E. Efficacy and Safety of
Rosuvastatin Plus Ezetimibe in High-Risk Patients: Results
from the EXPLORER Study. Paper presented at: International
Symposium on Atherosclerosis; 22 June, 2006; Rome, Italy.
3. Ridker PM et. al. for the Pravastatin or Atorvastatin
Evaluation and Infection Therapy - Thrombolysis in Myocardial
Infarction 22 (PROVE IT-TIMI 22) Investigators. C-Reactive
Protein Levels and Outcomes after Statin Therapy. N Engl J Med
2005;352:20-8.
4. American Heart Association. "Atherosclerosis." 2004. Available:
http://www.americanheart.org/presenter.jhtml?identifier=4440
5. Jones PH , Davidson MH, Stein EA et al. Am J Cardiol
2003;92:152-160.
6. Schuster H, Barter P, Stender S et al. Am Heart J
2004;147:705-712.
7. Blasetto JW, Stein EA, Brown WV et al. Am J Cardiol
2003;91(Suppl):3C-10C.
8. Berne C, Siewart-Delle A. Cardiovascular Diabetology 2005; 4:7
9. Betteridge JD, Gibson M. Atheroscler Suppl 2004;5(1):107, Abs
M464.
10. Davidson M, Ma P, Stein EA et al. Am J Cardiol
2002;89:268-275.
11. Schwartz GG, Bolognese MA, Tremblay BP et al. Am Heart J
2004;148(1):P105, H1-H9.
12. Olsson AG, Istad H, Luurila O et al. Am Heart J
2002;144:1044-1051.
13. Stalenhoef A, Ballantyne C, Sarti C et al. Eur Heart J
2005;26:2664-2672.
14. Strandberg TE, Freely J, Sigurdsson E. Clin Ther
2004;26(11):1821-1833.
15. Gupta M, Constance C. Atheroscler Suppl 2005;6(1):108-109 Abs
W16-P-033.
16. Fonseca FAH, Marotti M et al. Current Medical Research and
Opinion 2005;21 (8):1307-1315.
17. Jukema J, Liem A, Dunselman P et al. Current Medical Research
and Opinion 2005;21(11):1864-1876.
18. Clearfield M, Kallend D, Palmer M et al. Atheroscler Suppl
2005;6(1):104 Abs W16-P-014.
19. Wolffenbuttel B, Franken A, Vincent H et al. J Int Med
2005;257:531-539.
20. Paoletti R, Fahmy M, Mahla G et al. J Cardiovasc Risk
2001;8:383-390.
21. Brown W, Bays HE, Hassman DR et al. Am Heart J
2002;144:1036-1043.
22. Stein E, Strutt KL, Miller E, Southworth H. Am J Cardiol
2003;92:1287-1293.
23. Schneck DW, Knopp RH, Ballantyne CM et al. Am J Cardiol
2003;91:33-41.
24. Leiter LA, Palmer M, Kallend D et al. Atheroscler Suppl
2005;6(1):113 Abs W16-P-051.
25. Ballantyne C, Sosef F, Duffield E. Efficacy and Safety of
Rosuvastatin Plus Ezetimibe in High-Risk Patients: Results
from the EXPLORER Study. Atherosclerosis Supplements
2006;7(3):552 Abs Th-P16:270.
