The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study

Abstract

Backgruound: To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).

Methods: This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.

Results: A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).

Conclusion: In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Keywords: Cardiovascular diseases; Diabetes mellitus, type 2; Drug therapy, combination; Ezetimibe; Rosuvastatin calcium.

Fig. 1.

Primary endpoint. Comparison of the change of low-density lipoprotein cholesterol (LDL-C) rate (%) at 24 weeks. (A) Perprotocol set (PPS) and (B) full analysis set (FAS). LS, least square; R, rosuvastatin 20 mg; R/E, rosuvastatin 10 mg and ezetimibe 10 mg; CI, confidence interval. ^aP<0.05.

Fig. 2.

Secondary endpoints. (A) Changes of lipid profiles after 24 weeks. (B) Changes of homeostatic model assessment index. LDL-C, low-density lipoprotein cholesterol; LS, least square; R, rosuvastatin 20 mg; R/E, rosuvastatin 10 mg and ezetimibe 10 mg; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol; ApoB, apolipoprotein B; HOMA-IR, homeostasis model assessment of insulin resistance; HOMA-β, homeostasis model assessment of β-cell function. ^aP<0.05.