Comparison of the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy and Rosuvastatin Monotherapy on Lipoprotein in Patients With Type 2 Diabetes: Multicenter Randomized Controlled Study

Jiwoo Lee, You-Cheol Hwang, Woo Je Lee, Jong Chul Won, Kee-Ho Song, Cheol-Young Park, Kyu Jeung Ahn, Joong-Yeol Park, Jiwoo Lee, You-Cheol Hwang, Woo Je Lee, Jong Chul Won, Kee-Ho Song, Cheol-Young Park, Kyu Jeung Ahn, Joong-Yeol Park

Abstract

Introduction: Ezetimibe/statin combination therapy has been reported to provide additional cardioprotective effects compared to statin monotherapy. The apolipoprotein B/A1 (apoB/A1) ratio is an effective predictor of cardiovascular diseases. The aim of this study was to compare the efficacy and safety of rosuvastatin/ezetimibe combination therapy versus rosuvastatin monotherapy using the apoB/A1 ratio in patients with diabetes and hypercholesterolemia.

Methods: In this randomized, multicenter, open-label, parallel-group study, patients were randomly assigned to receive the combination therapy of rosuvastatin 5 mg/ezetimibe 10 mg once daily (n = 68) or monotherapy with rosuvastatin 10 mg once daily (n = 68), for 8 weeks.

Results: After the 8-week treatment, percentage change (least-square means ± standard error) in the apoB/A1 ratio in the rosuvastatin/ezetimibe group was significantly decreased compared to the rosuvastatin group (- 46.14 ± 1.58% vs. - 41.30 ± 1.58%, respectively; P = 0.03). In addition, the proportion of patients achieving > 50% reduction in low-density lipoprotein-cholesterol (LDL-C) and in the comprehensive lipid target (LDL-C < 70 mg/dL, non-HDL-cholesterol [non-HDL-C] < 100 mg/dL, and apoB < 80 mg/dL) was significantly different between the two groups (76.5 and 73.5% in the rosuvastatin/ezetimibe group and 47.1 and 45.6% in the rosuvastatin group, respectively; P < 0.001). The reduction in total cholesterol, non-HDL-C, LDL-C, and apoB were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group. Both treatments were well tolerated, and no between-group differences in drug-related adverse events were observed.

Conclusion: The apoB/A1 ratio was significantly reduced in patients receiving combination therapy with ezetimibe and rosuvastatin compared to those receiving rosuvastatin monotherapy. Both treatments were well tolerated in patients with type 2 diabetes and hypercholesterolemia.

Trial registration: NCT03446261.

Keywords: Apolipoprotein A1; Apolipoprotein B; Ezetimibe; Rosuvastatin.

Figures

Fig. 1
Fig. 1
Flow chart of patient distribution
Fig. 2
Fig. 2
Efficacy of rosuvastatin monotherapy versus rosuvastatin/ezetimibe combination therapy. a Percentage change in apolipoprotein B/apolipoprotein A1 (apoB/A1) ratio from baseline to week 8. Data in a are presented as least-square mean ± standard error; between-group treatment difference is given under the graph with the 95% confidence interval (CI) in parenthesis. b Proportion of patients achieving > 50% reduction in low-density lipoprotein-cholesterol (LDL-C) at 8 weeks. c Proportion of patients achieving comprehensive lipid target (LDL-C < 70 mg/dL, non-high-density lipoprotein-C < 100 mg/dL, and apoB < 80 mg/dL) without any adverse event-related drop-out. b, c Values immediately above bars are the number of patients with the percentage in parenthesis; the difference in responder’s proportion with the 95% CI in parenthesis are also shown above graphs. ***P < 0.001

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