Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Abstract

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

“…However, products of 3-hydroxy-3-methylglutaryl-coenzyme A are also utilized for essential biomaterials, and inappropriate statin prescriptions could result in statin-associated symptoms in the muscles, pancreas, and central nervous system [ 4 , 5 ]. Recently, a combination therapy comprised of statins and ezetimibe has demonstrated the potential to overcome limitations of statin monotherapy via the inhibition of intestinal cholesterol absorption and the increase of cholesterol excretion [ 6 ]. In addition, a PSCK9 inhibitor, a suppresser of hepatic LDLR expression, has also indicated potential in non-statin hypolipidemic therapy [ 7 ].…”

Molecular aspects of hypercholesterolemia treatment: current perspectives and hopes

“…It has been demonstrated that there is a large inconsistency in individual response to several different statins and doses. This rather unpredictable response is supposedly due to a complex interaction between genetic and environmental factors [45]. Combination of Ezetimibe-statins provides statistically significant improvements in triglycerides (TG), HDL-C, non-HDL-C, apolipoprotein B (ApoB) and high-sensitivity C-reactive protein (hs-CRP) [46].…”

Strategies for the use of nonstatin therapies

“…Additional benefits are achieved when ezetimibe is combined with atorvastatin or rosuvastatin [37][38][39][40]. Ezetimibe may also be combined with bile acid sequestrants, resulting in an additional reduction of LDL-C levels [29].…”