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At least 55 records · Page 3Linked to original sources
PubMed2006

Drug insight: the role of statins in combination with ezetimibe to lower LDL cholesterol.

The cardiovascular benefits of therapy with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are well documented. Undertreatment of dyslipidemia remains pervasive, however, and the introduction of more-aggressive optional LDL-cholesterol targets in US guidelines only heightens the challenges of reaching the target values. Combination therapy with a statin and the cholesterol absorption inhibitor ezetimibe could help in the management of patients who have an inadequate reduction in cholesterol after making changes to lifestyle or taking statins alone. The effects of the combination on cardiovascular risk remain speculative, however, and clinical trials are in development. In this Review we consider the rationale for combination therapy in the context of achieving LDL-cholesterol goals.

Anticholesteremic Agents↗
PubMed2005

An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis.

High levels of plasma apolipoprotein B-100 (apoB-100), the principal apolipoprotein of LDL, are associated with cardiovascular disease. We hypothesized that suppression of apoB-100 mRNA by an antisense oligonucleotide (ASO) would reduce LDL cholesterol (LDL-C). Because most of the plasma apoB is made in the liver, and antisense drugs distribute to that organ, we tested the effects of a mouse-specific apoB-100 ASO in several mouse models of hyperlipidemia, including C57BL/6 mice fed a high-fat diet, Apoe-deficient mice, and Ldlr-deficient mice. The lead apoB-100 antisense compound, ISIS 147764, reduced apoB-100 mRNA levels in the liver and serum apoB-100 levels in a dose- and time-dependent manner. Consistent with those findings, total cholesterol and LDL-C decreased by 25-55% and 40-88%, respectively. Unlike small-molecule inhibitors of microsomal triglyceride transfer protein, ISIS 147764 did not produce hepatic or intestinal steatosis and did not affect dietary fat absorption or elevate plasma transaminase levels. These findings, as well as those derived from interim phase I data with a human apoB-100 antisense drug, suggest that antisense inhibition of this target may be a safe and effective approach for the treatment of humans with hyperlipidemia.

Animals↗