Rosuvastatin plus ezetimibe gets 80% of high-risk patients to LDL cholesterol <70 mg/dL

September 11, 2006

September 11, 2006 (Barcelona, Spain) – The addition of ezetimibe (Zetia, Merck/Schering-Plough Pharmaceuticals) to statin therapy with rosuvastatin (Crestor, AstraZeneca) reduced LDL-cholesterol levels by 70%, allowing significantly more high-risk and very-high-risk patients to reach their LDL-cholesterol goals, a new study has shown [1]. In addition, the combination enabled more than half of treated patients to achieve the dual target of low LDL-cholesterol and low C-reactive-protein (CRP) levels.

These are the findings from the Examination of Potential Lipid-Modifying Effects of Rosuvastatin in Combination with Ezetimibe versus Rosuvastatin Alone (EXPLORER) study presented last week at the World Congress of Cardiology 2006 by Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX).

"The CRP reduction--a good solid reduction with rosuvastatin alone--went from 28% with rosuvastatin to 46% with the addition of ezetimibe," said Ballantyne. "It has also been put forth by the group at the Brigham and Women's Hospital that, based on an analysis of the PROVE-IT trial, it might be best to get your LDL and CRP levels down. In this dual target analysis, depending on how you define the targets, rosuvastatin alone got nearly 20% of patients down to LDL-cholesterol levels of less than 70 [mg/dL] and CRP levels down to less than 2.0 [mg/L]. [With the addition of] ezetimibe, more than half reached this dual target."

Hard end-point data still not here yet

EXPLORER was a six-week, open-label, randomized, parallel-group study conducted in 58 centers. Patients 18 years and older with hypercholesterolemia, a history of CHD, a CHD risk equivalent, or a 10-year CHD risk score >20% were included in the trial. The primary end point was the percentage of patients achieving the NCEP ATP III goal of LDL cholesterol <100 mg/dL after six weeks of treatment.

Treatment with the combination therapy reduced LDL cholesterol 70%, from 189 mg/dL at baseline to 56.9 mg/dL after six weeks. In contrast, treatment with rosuvastatin alone cut LDL levels by more than half, from 190.8 mg/dL at baseline to 81.5 mg/dL. CRP levels were also further reduced with the combination therapy, a reduction of 46% with rosuvastatin and ezetimibe vs a 28.6% reduction with rosuvastatin alone.

EXPLORER: Patients achieving NCEP ATP III treatment goals and low CRP levels
Rosuvastatin 40 mg, n=230 (%)
Rosuvastatin 40 mg and ezetimibe 10 mg, n=239 (%)
Who achieved LDL-cholesterol levels <100 mg/dL
Who achieved LDL-cholesterol levels <70 mg/dL
Who achieved LDL-cholesterol levels <100 mg/dL or 70 mg/dL (depending on risk category) and CRP levels <2 mg/L
Who achieved LDL-cholesterol levels 70 mg/dL and CRP levels <2 mg/L

"With the first big statin trial, the mean LDL-cholesterol level was 190 mg/dL, so this is a bit like that population," said Ballantyne. "Some might say, 'Well, you really can't get to less than 70 mg/dL,' but in fact, you can. Here, 80% on the combination of rosuvastatin and ezetimibe got to less than 70. This is an extrapolation, but if you look at what came out of REVERSAL and ASTEROID, in terms of maybe getting down to about 60 mg/dL or less for a regression of atherosclerosis, the mean LDL in this study is 57. We're going from 190 to 57, which is really quite remarkable. A little less than half of the patients got their LDL levels lower than their HDL cholesterol."

Both treatment arms were well tolerated, with no reported cases of myopathy, myositis, or rhabdomyolysis. However, as noted previously by heartwire , both rosuvastatin and ezetimibe still lack hard clinical end-point data. There are currently three morbidity and mortality studies ongoing with rosuvastatin: AURORA, CORONA, and JUPITER. AURORA is a study in patients with end-stage renal disease, CORONA a study in patients with symptomatic heart failure, and JUPITER is assessing rosuvastatin 20 mg in the primary prevention of cardiovascular events in 15 000 subjects with low LDL-cholesterol levels and elevated CRP levels.

1. Ballantyne CM, Sosef F, Duffield E, et al. Rosuvastatin plus ezetimibe for achievement of low-density lipoprotein cholesterol and C-reactive protein goals: results from the EXPLORER study. World Congress of Cardiology 2006; September 6, 2006; Barcelona, Spain. Poster 5390.

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