London, UK (6 September 2006) – C-reactive protein (CRP), a marker of inflammation and risk factor for cardiovascular disease was reduced by 46% in patients at high risk of a cardiovascular event in a new study presented today at the World Congress of Cardiology1.
The EXPLORER* study, which used a combination treatment regimen of Crestor (rosuvastatin) 40mg and ezetimibe 10mg also helped more than half (58%) of patients to meet dual CRP/LDL-C goals in just six weeks1. Both rosuvastatin and ezetimibe were well tolerated1.
What evidence is there to support the role of CRP in cardiovascular risk assessment?
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 risk of CV events. Inflammation of the arteries may lead to serious complications such as heart attacks and strokes2, and high levels of CRP may predict these risks years before they actually occur.
Individuals with elevated CRP can be up to 45% more likely to develop coronary heart disease3.
Previous clinical trials have demonstrated limited success in achieving dual CRP/LDL-C goals4, particularly for high-risk patients. The significant reductions in both markers seen in the EXPLORER study provide a new opportunity for high-risk patients to potentially reduce their cardiovascular risk with the combination therapy of rosuvastatin and ezetimibe.
What do the experts think?
Professor Chris Packard, Professor of Pathological Biochemistry, University of Glasgow commented: "Appropriately aggressive plasma lipid regulation is a critical component of personalised strategies for CHD prevention. Doctors now have available a range of therapies to match the needs of their patients. The results of EXPLORER add to the treatment options for patients at particularly high risk of CV disease. The study showed that the combination (of rosuvastatin and ezetimibe) not only lowered LDL-C in a highly effective manner, but also addressed the need to increase HDL-C and to reduce CRP".
- Key findings from EXPLORER:1, 5
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 rosuvastatin 40mg and ezetimibe 10mg compared with rosuvastatin monotherapy.
- Rosuvastatin and ezetimibe reduced CRP levels by 46% compared with 29% with rosuvastatin monotherapy.
- Rosuvastatin and ezetimibe 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 (2.6mmol/L) (94% vs 79%) and their European LDL-C goal (94% vs. 74%) at six weeks with rosuvastatin and ezetimibe compared with rosuvastatin monotherapy.
- Both rosuvastatin monotherapy and rosuvastatin combined with ezetimibe produced similar increases in HDL-C (8.5% vs. 10.8%).
- Rosuvastatin and ezetimibe were both well tolerated.
Understanding more about CRP
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 JUPITER6 (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) study, is to determine whether long-term treatment with rosuvastatin will reduce the risk for cardiovascular events in this patient population.
Professor James Shepherd , Professor of Vascular Biochemistry, Glasgow Royal Infirmary added "These results from EXPLORER are consistent with other earlier data showing that combination therapy with statins and ezetimibe significantly lowers the level of the inflammatory marker CRP in the plasma. The effect seems to derive primarily from the statin, and in this context, rosuvastatin monotherapy has already been shown to lower CRP. These findings bode well for the ongoing JUPITER trial".
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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 rosuvastatin would enable more patients with severely high cholesterol to achieve guideline lipid goals compared with rosuvastatin 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 mg1,5.
The results from EXPLORER add to the wealth of rosuvastatin efficacy data from its extensive GALAXY clinical trials programme, designed to address important unanswered questions in statin research and to investigate the impact of rosuvastatin 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.
Rosuvastatin has now received regulatory approvals in more than 75 countries across five continents. Over seven million patients have been prescribed rosuvastatin 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 rosuvastatin. Rosuvastatin should be used according to the prescribing information, which contains recommendations for initiating and titrating therapy according to the individual patient profile. The recommended starting dose of Rosuvastatin is 5 or 10mg.
1. Ballantyne C et al. 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. American Heart Association. "Atherosclerosis." 2004. Available: http://www.americanheart.org/presenter.jhtml?identifier=4440
3. Danesh J, Whicker JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe, GDO, Pepys MB, Gudnason V. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New Engl J Med. 2004:350:1387-1397.
4. 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.
5. Ballantyne C et al. 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.
6. Ridker PM et al. Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein. Rationale and design of the JUPITER trial. Circulation. 2003;108:2292-2297