Hypercholesterolemia: Clinical and MOA update on ezetimibe
Ezetimibe therapy: mechanism of action and clinical update.
Phan BA, Dayspring TD, Toth PP.
Vasc Health Risk Manag. 2012;8:415-27.
There is a clear association between elevated serum cholesterol levels and cardiovascular risk [1,2]. Treatment with statins effectively lowers LDL-C levels and reduces major cardiovascular events [3-7]. More aggressive lowering of LDL-C may increase cardiovascular benefit [8-10], especially in high-risk patients with multiple risk factors . To achieve optimal LDL-C levels, statin therapy alone might not be sufficient. In these patients, combination with other cholesterol-lowering agents is warranted, such as the cholesterol absorption inhibitor ezetimibe.
The mechanism of action, lipid effects, and safety of ezetimibe treatment are described as well as outcome trials that may impact its use in clinical practice.
Ezetimibe inhibits intestinal cholesterol absorption by selectively blocking the Niemann-Pick C1-like protein (NPC1L1) in the jejunal brush border, integral to the uptake of intestinal lumen micelles into the enterocyte [12-15]. It is, either in monotherapy or in combination with statins, effective in lowering cholesterol in several populations, such as insulin resistance, FH and sitosterolemia.
Both the SANDS and VYCTOR trial reported atherosclerosis regression [16-18]. The clinical efficacy of ezetimibe treatment was evaluated in the SEAS study  and in the SHARP trial , both using ezetimibe plus simvastatin (figure 1).
However, the ENHANCE  and ARBITER-6 trial  reported negative outcomes, although both trials were methodologically limited in their ability to evaluate the benefit of ezetimibe.
Therefore, the forthcoming results from the IMPROVE-IT trial  are highly anticipated. These results may better guide the use of ezetimibe in very high-risk CHD populations.
ConclusionYet, ezetimibe is a viable adjunct to statin therapy in the treatment of hypercholesterolemia. Forthcoming results are awaited to better judge its effect in clinical practice.
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