Abstract
The widespread clinical use of statins has contributed to significant reductions in the rate of cardiovascular morbidity and mortality over the past 3 decades, and statins are considered first-line therapy for the prevention and treatment of atherosclerotic vascular disease. Nevertheless, various other lipid-lowering agents can provide clinical benefit by supplementing or augmenting statin therapy in patients with severe hypercholesterolaemia or mixed dyslipidaemia, or by providing an alternative for patients who are intolerant to statins. Bile acid resins and niacin were prescribed for lipid modification for years before the introduction of the statins, and new data continue to emerge regarding their use in different patient groups and for specific conditions. Ezetimibe can be appropriate for patients whose primary lipid abnormality is an elevated LDL-cholesterol level, whereas the fibrates seem to be most beneficial in patients with low levels of HDL cholesterol and elevated triglycerides. At the end of 2012 and the beginning of 2013, the first microsomal triglyceride transfer protein inhibitor, lomitapide, and the first antisense therapy to target apolipoprotein B, mipomersen, were approved for the treatment of individuals with extremely elevated LDL-cholesterol levels caused by homozygous familial hypercholesterolaemia. Although two agents in the experimental class of cholesteryl ester transfer protein inhibitors have failed to show a benefit in clinical trials, newer drugs in this class could provide an additional strategy to address residual cardiovascular risk in patients treated with statins.
Key Points
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Statin therapy is the mainstay of lipid-lowering treatment, but residual cardiovascular risk remains unacceptably high in patients with coronary heart disease receiving optimal statin therapy
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Patients with statin intolerance, mixed dyslipidaemia, or an extremely elevated LDL-cholesterol level might benefit from additional LDL-cholesterol lowering therapies, or agents that favourably modify HDL-cholesterol and triglyceride levels
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Bile acid resins and ezetimibe can be used with or without statins to reduce LDL-cholesterol levels, although the clinical benefit of ezetimibe awaits the results of a randomized clinical trial
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Patients with homozygous familial hypercholesterolaemia might benefit from lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an antisense inhibitor of apolipoprotein B synthesis
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Niacin and fibrates help correct lipid abnormalities and can reduce cardiovascular risk in patients with a low HDL-cholesterol level, high triglyceride levels, or both
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Results of clinical trials with experimental cholesteryl ester transfer protein inhibitors are eagerly anticipated, and are expected to provide valuable data on the clinical benefit of pharmacologically raising HDL cholesterol
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A. M. Gotto is a stockholder/ Director of Aegerion and Arisaph Pharmaceuticals; he has acted as a consultant for AstraZeneca, Janssen, Kowa, Merck, and Roche; and is on the advisory board of DuPont and Vatera Capital. J. E. Moon declares no competing interests.
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Gotto, A., Moon, J. Pharmacotherapies for lipid modification: beyond the statins. Nat Rev Cardiol 10, 560–570 (2013). https://doi.org/10.1038/nrcardio.2013.117
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DOI: https://doi.org/10.1038/nrcardio.2013.117
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