Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe–statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia

Abstract

The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe-statin) doses and circulating non-cholesterol levels.

Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial

“…Our study is the fi rst to evaluate these effects over a longer term. The observed changes are consistent with recent results in patients with primary hypercholesterolemia treated with ezetimibe/simvastatin for 12 weeks (32) . This implies that short-term changes in noncholesterol sterol levels are likely to be sustained in the long term, similarly in FH patients as in patients with primary hypercholesterolemia.…”

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men

“…The literature contains several studies suggesting that statins increase cholesterol absorption ( 25 ). In this study, it was observed that simvastatin, at a dose of 20 mg taken for 7 weeks, increased the fractional cholesterol absorption by about 4%, which was not statistically signifi cantly different from placebo.…”

Effect of evolocumab on cholesterol synthesis and absorption

“…Although not measured in this study, an increase in free cholesterol secretion into the bile may account for this observation and should be followed up on in future studies. The modest effects on synthesis markers are in contrast with the increases in cholesterol synthesis markers seen in ezetimibe-treated patients and the decreases in these markers that have been reported with statins (10)(11)(12)(13)(14)(15)(16)(17)(18). These data indicate that the LDL-C reductions seen with evolocumab treatment are not due to decreased cholesterol production and that evolocumab, unlike ezetimibe, does not induce a compensatory response of increased cholesterol synthesis.…”