Abstract
The cardiovascular benefits of therapy with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are well documented. Undertreatment of dyslipidemia remains pervasive, however, and the introduction of more-aggressive optional LDL-cholesterol targets in US guidelines only heightens the challenges of reaching the target values. Combination therapy with a statin and the cholesterol absorption inhibitor ezetimibe could help in the management of patients who have an inadequate reduction in cholesterol after making changes to lifestyle or taking statins alone. The effects of the combination on cardiovascular risk remain speculative, however, and clinical trials are in development. In this Review we consider the rationale for combination therapy in the context of achieving LDL-cholesterol goals.
Key Points
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The cardiovascular-risk-reducing effects of statins compared with placebo have been demonstrated in several trials. Ezetimibe, a member of the class of cholesterol absorption inhibitors, can reduce LDL-cholesterol level when used as monotherapy and can accentuate LDL-cholesterol reduction when combined with statins.
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Optional lower targets for LDL cholesterol proposed by recent guidelines will require intensified treatment, which could necessitate greater use of combination therapies such as statins plus ezetimibe.
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Preliminary data from a single-pill preparation of simvastatin plus ezetimibe indicate greater achievement of treatment goals for LDL cholesterol compared with statin monotherapy.
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Trials are in progress to evaluate the effect of this combination on clinical and other endpoints.
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Acknowledgements
The authors wish to acknowledge the assistance of J Jou, in the editorial preparation of this manuscript.
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Competing interests
Dr Gotto discloses that he has served as a consultant for Merck-Schering Plough, the company that markets ezetimibe and ezetimibe/simvastatin. He also has served as a consultant for the following companies with interests in lipid-lowering medications: AstraZeneca Pharmaceuticals, Bristol Myers-Squibb, Co., Johnson & Johnson Merck, Kos Pharmaceuticals, Kowa, Merck & Co, Inc., Novartis, Pfizer, Inc., and Reliant Pharmaceuticals.
JA Farmer declared he has no competing interests.
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Gotto, A., Farmer, J. Drug Insight: the role of statins in combination with ezetimibe to lower LDL cholesterol. Nat Rev Cardiol 3, 664–672 (2006). https://doi.org/10.1038/ncpcardio0711
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DOI: https://doi.org/10.1038/ncpcardio0711
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