Lipid-lowering: can ezetimibe help close the treatment gap?

Abstract

Most patients who should be on lipid-lowering therapy are not receiving it, and most patients who are receiving it are not reaching their appropriate low-density lipoprotein (LDL) goals. This is in part because physicians and patients fear side effects of statins and other lipid-lowering agents. Ezetimibe (Zetia), a new lipid-lowering drug, may help physicians close this "treatment gap" in more patients, especially in combination with a statin. s KEY POINTS Ezetimibe works by inhibiting cholesterol absorption. It has a favorable side-effect profile; in particular, it does not cause hepatotoxicity or myositis, which, although uncommon, are concerns with statin therapy. Ezetimibe lowers LDL levels by about 18% when used as monotherapy and by an additional 25% when added to statin therapy. The most practical use of ezetimibe will be in combination with ongoing statin therapy in patients who have not reached their LDL goals. Ezetimibe monotherapy may be used when the patient cannot tolerate statin therapy or does not wish to use a statin. Goal LDL levels are less than 100 mg/dL for patients at high risk, less than 130 for patients at moderate risk, and less than 160 for patients at low risk.

Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease

“…In addition, there may be patient or physician reluctance to increase the dose of statins or other lipid-lowering drugs (e.g., fibrates, niacin, bile acid sequestrants) due to safety and tolerability concerns, or concern over the cost or inconvenience of repeated patient visits [14][15][16][17]. Therefore, a therapy that is effective, tolerable and also increases the likelihood of achieving LDL-C treatment targets would be desirable.…”

Burkholderia cenocepacia: a new biocatalyst for efficient bioreduction of ezetimibe intermediate

“…Ezetimibe (SCH 58235, 1-(4-fluorophenyl)-3-(R)-[3-(4-fluorophenyl)-3-(S)-hydroxypropyl]-4-(S)-(4-hydroxyphenyl)-2-azetidinone), a selective inhibitor of acyl-coenzyme A: cholesterol acyltransferase (ACAT), reduces plasma LDL cholesterol level and increases plasma HDL level [4][5][6]. Synthesis of ezetimibe involves reduction of 1-(4-fluorophenyl)-5-(2-oxo-4-phenyl-oxazolidin-3-yl)-pentane-1,5-dione (FOP dione) to crucial homochiral intermediate 3-[5-(4-fluorophenyl)-5-(S)-hydroxypentanoyl]-4(S)-4-phenyl-1,3-oxazolidin-2-one (FOP alcohol), which is further processed to synthesize ezetimibe ( Fig.…”

Inhibition of synthesis and absorption of cholesterol: A new option in managing hypercholesterolemia

“…Over half (52%) of patients did not achieve LDL-C goal on the initial dose of statin, and 86% of these patients had still not reached goal after 6 months [13]. Thus, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice [14].…”