A New Class In Cholesterol Management

Br J Cardiol 2004;11(Suppl 3):S1-S30 Leave a comment
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Over the past 15 years, a number of randomised controlled trials have shown that lowering the low-density lipoprotein (LDL) cholesterol results in a reduction in coronary heart disease (CHD) events. There appears to be a continuous relationship between vascular risk and plasma cholesterol levels, with no lower threshold level.

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We are not hitting lipid targets in patients who are at high risk of cardiovascular events. For example, EUROASPIRE II data show that 58% of coronary patients had not achieved a total cholesterol below 5 mmol/L despite intervention. Statins are very successful in targeting cholesterol synthesis in the liver but we face the challenge of moving therapy back to the first-line organ in cholesterol metabolism, the gut.

The management of dyslipidaemia is likely to follow the example of hypertension. Better regulation of the lipid profile will be achieved using a combination of drugs that have actions on various parts of the cholesterol homoeostatic pathway.

Intestinal-acting cholesterol-lowering agents include the bile acid sequestrants, which have marked gastro-intestinal side effects; and the plant stanol and sterol esters, which lack selectivity and are expensive. Another agent is needed that is effective without these side effects of poor tolerability, lack of selectivity, non-compliance and expense. Cholesterol absorption inhibitors, such as ezetimibe, target the exogenous cholesterol pathway. Their effects are complementary and additive to those of statins. Ezetimibe is a potent and specific inhibitor of dietary and biliary cholesterol absorption.

It is also a cholesterol uptake inhibitor. It does not affect the absorption of bile acids or fat-soluble vitamins. Ezetimibe and its glucuronide metabolite circulate enterohepatically, which means that there is little peripheral exposure to these compounds.

In animal studies, ezetimibe has been shown to lower plasma cholesterol and to inhibit the development of atherosclerosis. In clinical studies, ezetimibe co-administered with low-dose statin may give an additional 10% reduction in triglycerides, 14% reduction in LDL, and a 5% rise in high-density lipoprotein (HDL) cholesterol compared to treatment with statin alone. In one study, significantly better NCEP goal reduction was achieved with co-administration of ezetimibe and statin compared to statin alone.

Disclaimer: UK prescribing information current at the date of publication of this supplement can be found by downloading the PDF. Medinews Cardiology Limited advises healthcare professionals to consult up-to-date Prescribing Information and the full Summary of Product Characteristics available from the manufacturers before prescribing any product. Medinews Cardiology Limited cannot accept responsibility for any errors in prescribing which may occur.
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