Multiply doses of FDC of rosuvastatin and ezetimibe versus rosuvastatin monotherapy in Chinese patients with hypercholesterolemia (ROSE-CH): multicenter, randomized-controlled trial

OBJECTIVE: Rosuvastatin plus ezetimibe improves the lipid-lowering effect through different mechanisms of action. This study intended to compare the efficacy and safety of the fixed-dose combination (FDC) of rosuvastatin/ezetimibe vs. rosuvastatin alone in hypercholesterolemia patients. METHODS: ROSE-CH (ROSuvastatin and Ezetimibe in Chinese Hypercholesterolemia patients) was a multicenter, randomized, double-blind, positive drug-controlled, superiority-tested phase III clinical trial; 743 patients were randomized into rosuvastatin/ezetimibe 10/10 mg, 5/10 mg, and 2.5/10 mg groups, as well as rosuvastatin 10 mg and 5 mg groups at a 1:1:1:1:1 ratio. A total of 143, 127, 263, and 137 patients had low, intermediate, high, and very-high baseline atherosclerotic cardiovascular disease (ASCVD) risks. The study period spanned from December 24, 2021, to December 6, 2022. RESULTS: Efficacy and safety assessments were conducted in 670 and 696 patients. Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week (W)12 was greater in the rosuvastatin/ezetimibe 10/10 mg group vs. rosuvastatin 10 mg group [least-squares means (LSmean): -51.48% vs. -42.47%], rosuvastatin/ezetimibe 5/10 group vs. rosuvastatin 5 mg group (LSmean: -50.08% vs. -40.17%), and rosuvastatin/ezetimibe 2.5/10 mg group vs. the rosuvastatin 5 mg group (LSmean: -48.47% vs. -40.17%) (all P < 0.001). The same trend was observed for the percentage change in LDL-C from baseline to W4 and W8 (all P < 0.001). In patients with baseline very high ASCVD risk, the achievement of LDL-C target at W12 was higher in rosuvastatin/ezetimibe 10/10 mg vs. rosuvastatin 10 mg groups and rosuvastatin/ezetimibe 2.5/10 mg vs. rosuvastatin 5 mg groups (both P < 0.05). The incidence of adverse events was 36.0%, 38.7%, 25.2%, 31.4%, and 38.6% in each group. Regarding serious adverse events, the incidence was 2.2%, 2.9%, 0.7%, 3.6%, and 0.7% in each group. The incidence of drug-related adverse events was relatively high, which was 26.6%, 31.4%, 18.5%, 23.6%, and 29.0% in each group, respectively, irrespective of the absence of serious drug-related adverse events. CONCLUSION: The FDC of rosuvastatin/ezetimibe has superior LDL-C-lowering effects over rosuvastatin alone, with good safety profiles in hypercholesterolemia patients.