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Add-On Cholesterol Therapy Using Ezetimibe May Be More Effective Than Alternative Therapies Due to Pharmacological Synergy: Presented at ACCP

By Maggie Schwarz

PHILADELPHIA -- September 18, 2008 -- "Prescribing ezetimibe along with a statin affords more than just additivity, but perhaps synergy in lowering cholesterol, according to results of a study presented here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting.

Michael J. Zema, MD, State University of New York at Stony Brook, Stony Brook, New York, reported on September 15 on a comparison of ezetimibe versus colesevelam as add-on therapy to a statin.

"I hypothesised that ezetimibe plus a statin would lower low-density lipoprotein (LDL) cholesterol more than you would predict on the basis of additivity alone," explained Dr. Zema. "That is, there may be true synergy of effect when using these agents together."

For the study, Dr. Zema randomised 14 patients who were previously receiving statin therapy to the addition of either ezetimibe or colesevelam. After 6 weeks of therapy, patients were crossed over to the alternative add-on therapy.

Both add-on therapies produced significant reductions in LDL and non-high-density lipoprotein (HDL) cholesterol (P < .001). Add-on ezetimibe, however, resulted in significantly greater reduction in LDL cholesterol than add-on colesevelam (-28.3% vs -21.0%, respectively; P < .02).

Add-on ezetimibe also reduced non-HDL cholesterol significantly more than add-on colesevelam (-25.6% vs -15.2%, respectively, P < .001). Both add-on medications reduced total cholesterol, LDL:HDL ratio, and non-HDL:HDL ratio significantly.

Dr. Zema concluded that both ezetimibe and colesevelam are effective add-on therapies to statins. Add-on ezetimibe, however, was significantly more effective than add-on colesevelam in reducing LDL cholesterol, despite similar reported median decreases in LDL cholesterol using either agent.

"Though the number of patients we studied was small, our results are consistent with those reported in other small prospective pilot studies, and the study was adequately powered using statistical methods to disprove multiple null hypotheses," Dr. Zema remarked.

Dr. Zema said the superior further improvement in the lipid profile using add-on ezetimibe is consistent with pharmacodynamic synergy, as opposed to mere additivity, between ezetimibe and statins. "This synergy may be related to blockade by ezetimibe of statin-induced upregulation of intestinal cholesterol absorption."


[Presentation title: Ezetimibe Add-On Therapy for Hypercholesterolemia: Additivity or Synergy? Abstract 3]

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