Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe)

Kyung-Jin Kim, Sang-Hyun Kim, Young Won Yoon, Seung-Woon Rha, Soon-Jun Hong, Choong-Hwan Kwak, Weon Kim, Chang-Wook Nam, Moo-Yong Rhee, Tae-Ho Park, Taek-Jong Hong, Sungha Park, Youngkeun Ahn, Namho Lee, Hui-Kyung Jeon, Dong-Woon Jeon, Kyoo-Rok Han, Keon-Woong Moon, In-Ho Chae, Hyo-Soo Kim, Kyung-Jin Kim, Sang-Hyun Kim, Young Won Yoon, Seung-Woon Rha, Soon-Jun Hong, Choong-Hwan Kwak, Weon Kim, Chang-Wook Nam, Moo-Yong Rhee, Tae-Ho Park, Taek-Jong Hong, Sungha Park, Youngkeun Ahn, Namho Lee, Hui-Kyung Jeon, Dong-Woon Jeon, Kyoo-Rok Han, Keon-Woong Moon, In-Ho Chae, Hyo-Soo Kim

Abstract

Aim: We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS).

Method: This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily).

Results: Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients.

Conclusion: Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS.

Keywords: Cholesterol; Diabetes mellitus; Ezetimibe; Hypercholesterolemia; Metabolic syndrome; Rosuvastatin.

© 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Participant distribution. FAS, full analysis set; E10, ezetimibe 10 mg; R5, rosuvastatin 5 mg; R10, rosuvastatin 10 mg; R20, rosuvastatin 20 mg
Figure 2
Figure 2
LDL cholesterol levels at baseline and after treatment. Bars represent standard errors; LDL, low‐density lipoprotein; E, ezetimibe 10 mg; R5, rosuvastatin 5 mg; R10, rosuvastatin 10 mg; R20, rosuvastatin 20 mg
Figure 3
Figure 3
Comparison of the percent changes in LDL cholesterol, TG, and HDL cholesterol between monotherapy and combo therapy for 8 wk: pooled data and data of the three different doses. Bars represent standard errors; LDL, low‐density lipoprotein; TG, triglyceride; HDL, high‐density lipoprotein; LS means, least‐squares means; R, rosuvastatin (pooled); E, ezetimibe 10 mg; R5, rosuvastatin 5 mg; R10, rosuvastatin 10 mg; R20, rosuvastatin 20 mg. *P<.05 for the specified between‐treatment difference
Figure 4
Figure 4
Greater reduction in cholesterol observed in patients with DM than in non‐DM patients receiving combo therapy. Among patients receiving combo therapy, patients with DM exhibited greater reductions in cholesterol compared to non‐DM patients, whereas patients with DM and non‐DM patients receiving monotherapy showed comparable levels of cholesterol reduction. Bars represent standard errors; DM, diabetes mellitus; LDL‐C, low‐density lipoprotein cholesterol; non‐HDL‐C, non‐high‐density lipoprotein cholesterol; Apo B, apolipoprotein B; TC, total cholesterol; R, rosuvastatin; E, ezetimibe. *P<.05 for the specified between‐treatment difference
Figure 5
Figure 5
Greater reduction in cholesterol in patients with MetS vs non‐MetS patients receiving combo therapy. Among patients receiving combo therapy, patients with MetS showed greater reductions in cholesterol compared to non‐MetS patients, whereas comparable reductions in cholesterol were observed in patients with MetS vs non‐MetS patients receiving monotherapy. Bars represent standard errors; MetS, metabolic syndrome; LDL‐C, low‐density lipoprotein cholesterol; non‐HDL‐C, non‐high‐density lipoprotein cholesterol; Apo B, apolipoprotein B; TC, total cholesterol; R, rosuvastatin; E, ezetimibe. *P<.05 for the specified between‐treatment difference

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