New lipid-lowering agents include microsomal triglyceride transfer protein (MTP) inhibitors, which may have a role in the treatment of hypercholesterolemia. Clinical applications of MTP inhibitors have been focused primarily on high-dose monotherapy to produce substantial reductions in LDL-cholesterol levels (particularly for patients with homozygous familial hypercholesterolemia). However, this strategy has been associated with a high rate and severity of gastrointestinal and hepatic adverse events that has prohibited the use of these agents. Data suggest the LDL-cholesterol-lowering efficacy of low-dose lomitapide (AEGR-733, formerly BMS-201038), under development by Aegerion Pharmaceuticals Inc, in patients with familial hypercholesterolemia, both as a single agent and in combination with commonly prescribed lipid-lowering therapies. MTP inhibition with lomitapide may offer a treatment option for patients who cannot tolerate statin therapy or who experience insufficient LDL-cholesterol reduction with available therapies. However, the safety concerns for MTP inhibitors for the treatment of hyperlipidemia must be fully addressed, and the assessment of the risk-to-benefit ratio for MTP inhibitors in patients at different levels of cardiovascular-disease risk is required before clinical use of this class of drugs may be recommended. © Thomson Reuters (Scientific) Ltd.
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