Two-Drug Combination May Improve Lipid Goals

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STOCKHOLM—New results suggest that combination therapy with ezetimibe/simvastatin, when prescribed at the recommended starting and next higher doses, is more likely to improve lipids than atorvastatin alone in patients with metabolic syndrome. The dual regimen also is more likely to help patients achieve lipid targets.

In addition, the data, reported at the 46th European Association for the Study of Diabetes meeting, show that the combination treatment is superior to the atorvastatin alone whether or not the patient has atherosclerotic vascular disease (AVD).

“Since doctors don't do a great job of titrating statins, knowing that the starting dose of ezetimibe/simvastatin is superior to the starting dose of atorvastatin in this population is of interest,” principal investigator Jeffrey B. Rosen, MD, Medical Director of Clinical Research of South Florida in Coral Gables, told Renal & Urology News.

Dr. Rosen and colleagues evaluated subgroups of metabolic syndrome patients with and without AVD to assess the percent change from baseline in lipid, lipoprotein, and high-sensitivity C-reactive protein (hs-CRP) levels with ezetimibe/simvastatin combination therapy versus atorvastatin alone. The group also determined the percentage of patients with and without AVD treated with ezetimibe/simvastatin combination therapy versus atorvastatin who achieved specified lipid and hs-CRP levels.
The analysis included 1,143 adult patients who were randomized to receive ezetimibe/simvastatin combination tablets 10/20 or 10/40 mg or atorvastatin 10, 20, or 40 mg for six weeks as part of the Vytorin in Metabolic Syndrome  (VYMET) study.  All patients had metabolic syndrome and hypercholesterolemia and were at moderately high risk of coronary heart disease (CHD).

The National Cholesterol Education Program Adult Treatment Panel III recommends low-density lipoprotein cholesterol (LDL)-C below 100 mg/dL for individuals at high risk for CHD, such as those with both AVD and metabolic syndrome. In addition, a joint statement from the American Diabetes Association and American College of Cardiology suggested that individuals at high risk and very high risk for CHD achieve apolipoprotein (Apo) B levels below 90 or below 80 mg/dL, respectively. When patients are unable to reach target cholesterol levels with lifestyle changes, statins are typically prescribed as first-line therapy. If patients do not achieve targets with statin therapy, a second agent may be considered.

Prespecified dose comparisons in the present analysis were ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 mg or 20 mg and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg.
Significantly more patients without AVD achieved the target LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), Apo B level, and the composite of these three measures with ezetimibe/simvastatin versus atorvastatin for the specified dose comparisons, except in the ezetimibe 10 mg/simvastatin 40 mg versus atorvastatin 40 mg dose comparison.  An LDL-C below 100 mg/dL, non-HDL-C below 130 mg/dL, Apo B below 90 mg/dL, and the composite were achieved in 90%, 87%, 65%, and 65% of patients who received ezetimibe 10 mg/simvastatin 20 mg compared with 70%, 63%, 41%,  and 41% of patients who were treated with atorvastatin 10 mg.  The percentages were 90%, 87%, 65%, and 65% in patients who received ezetimibe 10 mg/simvastatin 20 mg compared with 76%, 73%, 49%, and 49% of patients who were treated with atorvastatin 20 mg.  The differences on all measures between patients who received ezetimibe 10 mg/simvastatin 40 mg and atorvastatin 40 mg were non-significant.

Significantly more patients with AVD achieved the target LDL-C level, non-HDL-C level, and the composite of LDL-C, non-HDL-C, and Apo B levels with ezetimibe/simvastatin than with atorvastatin at all dose comparisons. In addition, significantly more patients with AVD achieved the target Apo B level with the ezetimibe 10 mg/simvastatin 20 mg versus atorvastatin 10 mg comparison.

In both subgroups, achievement of hs-CRP below 2.0 mg/L was similar with both treatments for all dose comparisons.
Both treatments were generally well tolerated in patients with and without AVD.

“Our results show greater achievement of specified LDL-C, non-HDL-C and Apo B levels based on cardiometabolic risk both individually and combined, in patients with hyperlipidemia and metabolic syndrome if patients receive the combination [ezetimibe/simvastatin] in lieu of the statin alone at starting doses,” Dr. Rosen observed.

He emphasized that a reduction in cardiovascular outcomes through treatment with ezetimibe/simvastatin or hs-CRP lowering has not been proven.

Finally, Dr. Rosen said the study has an important message for CKD patients. “Patients with CKD are at high risk for CHD, and CHD is a major cause of death in CKD patients,” he noted.  “Therefore, controlling all of their risk factors, including lipids, is very important.”

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