Drug Treatment of Hyperlipidaemia
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- Toth, P.P. Drugs (2010) 70: 1363. doi:10.2165/10898610-000000000-00000
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Mammalian sterol and lipid metabolism depends on a large number of highly evolved biochemical and histological processes responsible for the absorption, distribution and steady-state anabolic/catabolic handling of these substances. Lipoproteins are complex polymolecular assemblies comprising phospholipids, cholesterol and cholesterol esters, triglycerides and a variety of apolipoproteins. The primary function of lipoproteins is to facilitate the systemic distribution of sterols and lipids. Abnormalities in lipoprotein metabolism are quite common and are attributable to a large number of genetic mutations, metabolic derangements such as insulin resistance or thyroid dysfunction, and excess availability of cholesterol and fat from dietary sources. Dyslipidaemic states facilitate endothelial dysfunction and atherogenesis. Dyslipidaemia is recognized as a risk factor for cardiovascular disease in both men and women, and people of all racial and ethnic groups throughout the world. Dyslipidaemia is modifiable with dietary change and the use of medications that impact on lipid metabolism through a variety of mechanisms. Reducing atherogenic lipoprotein burden in serum is associated with significant and meaningful reductions in risk for a variety of cardiovascular endpoints, including myocardial infarction, ischaemic stroke, development of peripheral arterial disease and mortality.
This review provides an overview on how to best position lipid-lowering drugs when attempting to normalize serum lipid profiles and reduce risk for cardiovascular disease. HMG-CoA reductase inhibitors (statins) are widely accepted to be the agents of choice for reducing serum levels of low-density lipoprotein cholesterol (LDL-C) in both the primary and secondary prevention settings. Ezetimibe and bile acid sequestrants are both effective agents for reducing LDL-C, either used alone or in combination with statins. The statins, fibric acid derivatives (fibrates) and niacin raise high-density lipoprotein cholesterol to different extents depending upon genetic and metabolic background. Fibrates, niacin and omega-3 fish oils are efficacious therapies for reducing serum triglycerides. Combinations of these drugs are frequently required for normalizing mixed forms of dyslipidaemia.