Effects of Statin versus the Combination of Ezetimibe plus Statin on Serum Lipid Absorption Markers in Patients with Acute Coronary Syndrome

Abstract

Background. The use of statins is essential for aggressive lipid-lowering treatment in acute coronary syndrome (ACS) patients with dyslipidemia. Recently, elevation of sitosterol, a lipid absorption marker, was reported to be associated with premature atherosclerosis. The purpose of the present study was to examine the impact of ezetimibe, a selective intestinal cholesterol transporter inhibitor, in ACS patients. Methods. A total of 197 ACS patients were randomized to pitavastatin + ezetimibe (n = 100) or pitavastatin (n = 97). Low-density lipoprotein cholesterol (LDL-C) and sitosterol levels were evaluated on admission and after 12 weeks. Results. After 12 weeks, the pitavastatin + ezetimibe group showed a significantly greater decrease of sitosterol (baseline versus after 12 weeks; 2.9 ± 2.5 versus 1.7 ± 1.0 ng/mL, P < 0.001) than the pitavastatin group (2.7 ± 1.5 versus 3.0 ± 1.4 ng/mL). The baseline sitosterol level was significantly higher in patients with achieved LDL-C levels ≥ 70 mg/dL than in patients with levels < 70 mg/dL (3.2 ± 2.5 versus 2.4 ± 1.3 ng/mL, P = 0.006). Conclusions. Ezetimibe plus statin therapy in ACS patients with dyslipidemia decreased LDL-C and sitosterol levels more than statin therapy solo. Sitosterol Elevation was a predictor of poor response to aggressive lipid-lowering treatment in ACS patients.

Figure 1

After 12 weeks of treatment, the serum levels of LDL-C and TC show a significant decrease in the pitavastatin + ezetimibe group compared to the pitavastatin group. In terms of the serum levels of HDL-C and TG, there are no significant changes in each group.

Figure 2

After 12 weeks of treatment, the serum levels of sitosterol and campesterol show a significant decrease in the pitavastatin + ezetimibe group compared to the pitavastatin group. The serum level of lathosterol decreases in both groups, but there is no significant difference between the two groups.

Figure 3

The achievement rate of LDL-C less than 100 mg/dL is the recommended target of the Japan Atherosclerosis Society guidelines, and the achievement rate of LDL-C less than 70 mg/dL is the recommended target of Adult Treatment Panel III (ATPIII) and European Atherosclerosis Society (EAS) guidelines. In each analysis, the achievement rate is significantly higher in the pitavastatin + ezetimibe group than in the pitavastatin group.

Figure 4

(a) The baseline levels of cholesterol synthesis and absorption markers according to the LDL-C levels at 12 weeks irrespective of treatment methods. The baseline levels of sitosterol and campesterol are significantly higher in patients whose LDL-C levels at 12 weeks are greater than or equal to 100 mg/dL than in patients whose LDL-C levels at 12 weeks are less than 100 mg/dL. In terms of the baseline level of lathosterol, there is no significant difference. (b) The results are the same when the cut-off of LDL-C is defined as less than 70 mg/dL at 12 weeks.

Figure 5

The impacts of baseline levels of sitosterol and lipid-lowering treatment strategy. (a) The achievement rate of LDL-C less than 100 mg/dL and (b) less than 70 mg/dL (b) in each treatment group whose baseline sitosterol is equal to or more than 2.2 μg/mL. (c) The achievement rate of LDL-C less than 100 mg/dL and (d) less than 70 mg/dL in each treatment group whose baseline sitosterol is less than 2.2 μg/mL.