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Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia

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Abstract

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged ≥18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for ≥6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of −25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides −14.0%) compared with LDL cholesterol −3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides −2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.

Section snippets

Study population:

Prospective patients with primary hypercholesterolemia were provided information about the trial, had questions answered, and signed an informed consent. The patient population consisted of adults ≥18 years of age, currently taking a stable daily dose of a statin for ≥6 weeks. Patients must have been previously instructed on a cholesterol-lowering diet. Each patient’s mean LDL cholesterol level, calculated from 2 separate determinations during screening (visits 1 and 2), had to be at or above

Demographic and baseline characteristics and patient disposition:

Between December 2000 and April 2001, 769 patients taking statin monotherapy were randomized to treatment with either the addition of ezetimibe 10 mg/day (n = 379) or matching placebo (n = 390) at 80 study centers (51 United States centers, 29 international). Patient demographics and baseline characteristics are listed in Table 1. Treatment groups were generally balanced with respect to age, gender, race, diet, weight, and body mass index. Approximately 68% of patients had coronary heart

Discussion

The objective of the present study was to evaluate the efficacy and safety of ezetimibe when added to ongoing statin therapy in a population of patients at high cardiovascular risk who had not achieved their recommended LDL cholesterol goal. The results indicate that a clinically meaningful reduction in LDL cholesterol occurs when ezetimibe is added to ongoing statin therapy. Moreover, this reduction is associated with achievement of the treatment goal in a substantial number of patients not

Acknowledgements

We wish to thank Arlene Reiss, BS, and Ken Youngren, PhD, for assisting in the preparation of this manuscript.

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    This trial was funded by MSP Singapore Company, LLC, a joint venture between Schering Corporation and Merck & Co., North Wales, Pennsylvania.

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    A complete list of participants appears in the Appendix.

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