McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 4 7 Lipid-lowering agents

Therapeutic actions and indications Ezetimibe works in the brush border of the small intes- tine to decrease the absorption of dietary cholesterol from the small intestine. As a result, less dietary cho- lesterol is delivered to the liver, and the liver increases the clearance of cholesterol from the serum to make up for the drop in dietary cholesterol, causing the total serum cholesterol level to drop. See Table 47.3 for usual indications. Pharmacokinetics Ezetimibe is absorbed well after oral administration, reaching peak levels in 4 to 6 hours. It is metabolised in the liver and the small intestine, with a half-life of 22 hours. Excretion is through faeces and urine. It is not known whether the drug crosses the placenta or enters breast milk. Contraindications and cautions Ezetimibe is contraindicated in people with an allergy to any component of the drug to avoid hypersensitivity reactions . If it is used in combination with a statin, it should not be used during pregnancy or breastfeeding or with severe liver disease because of the known effects of statins, including possible liver problems and renal failure. The drug should be used with caution as mono- therapy during pregnancy or breastfeeding because the effects on the fetus or neonate are not known and with elderly people or individuals with liver disease because of the potential for adverse reactions. reduction in cardiac events. Based on these data, this means that in a large study, 3% of the people receiving no drugs suffered a cardiac event, whereas only 2% of the people taking atorvastatin suffered a cardiovascular event.This translates into one less heart attack in every 100 people over a 3-year period.The other 99 people taking the drug had no measurable benefit from the drug. The number needed to treat to show effectiveness is very high. Other lipid-lowering drugs show similar or even worse statistics. Should our heathcare focus so heavily, then, on lowering cholesterol and lipid levels?Those who feel that it should argue that with large numbers of people using these drugs, the number of people who are saved from a cardiovascular event is actually higher. Those who are now questioning it wonder whether the cost and adverse effects associated with the drugs are justified for benefiting such a small percentage of people. At the moment, this seems to be the best we have to offer people, but as more research is done on the process of CAD, standards may change.

KEY POINTS

■■ HMG-CoA reductase inhibitors, or statins, block the enzyme HMG-CoA reductase, resulting in lower serum cholesterol levels, a resultant breakdown of LDLs and a slight increase in HDLs. ■■ Individuals receiving HMG-CoA reductase inhibitors should avoid pregnancy because of serious fetal adverse effects; should take the drug in the evening to mimic the normal patterns of lipid formation; should have liver function monitored regularly; and should be instructed to report any sudden muscle pain, especially if accompanied by fever. C holesterol absorption inhibitors The first of a new class of drugs to lower cholesterol levels was approved in 2003—ezetimibe ( Ezetrol ). Cur- rently there is controversy about cholesterol-lowering drugs, specifically ezetimibe, because of the ENHANCE study (full title of the study: Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Subjects With Heterozygous Familial Hypercholesterolaemia). This study, released in January 2008, looked at the actual post-marketing benefits of antihyperlipidaemic therapy. The study failed to find any positive benefit from the addition of ezetimibe to a statin. This finding called into question the whole class of cholesterol-lowering drugs and the benefits or lack of benefits associated with this therapy (Box 47.7). Further studies are needed. The ENHANCE Study Modifying the risk factors established through the Framingham Study remains the key to the prevention of CAD. If, statistically, risk factors can be reduced, the chances of a cardiovascular event will be smaller.The actual process of atheroma development and vessel occlusion remains elusive, and the role of cholesterol and lipids in the actual process is not clearly understood. Lowering the cholesterol and lipid levels, although putting the person into a statistically lower risk group, does not seem to really offer much protection against cardiovascular events in people who have not already experienced an event. Watching the television ads or reading magazine ads for the lipid-lowering drugs, you will notice a disclaimer that states that “these drugs have not been proven to reduce your risk of heart disease or heart attack”. When the ENHANCE study was published in 2008, showing that the use of ezetimibe and simvastatin did not slow the progression of atheromas, the action of other lipid-reducing drugs was called into question.The data on the effectiveness of atorvastatin claims a 36% The evidence BOX 47.7