Lipid profile and safety of rosuvastatin monotherapy versus rosuvastatin plus ezetimibe in high risk coronary artery disease: a systematic review and meta-analysis of randomized controlled trials

Background: Combining lipid-lowering agents may enhance outcomes in patients with high-risk coronary artery disease. While rosuvastatin is known to reduce LDL-C and cardiovascular events, the additional benefit of ezetimibe remains under investigation. This meta-analysis evaluated the efficacy and safety of RSV combined with EZ compared to RSV monotherapy in high-risk coronary artery disease. Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar up to August 30, 2024. Data were analyzed using a random-effects model in Review Manager 5.4. Lipid profile and safety outcomes were assessed in accordance with PRISMA guidelines. Results: Combination therapy with rosuvastatin and ezetimibe significantly improved the lipid profile in high-risk coronary artery disease patients compared to rosuvastatin monotherapy, based on 11 studies with 1,963 subjects. Treatment with RSV plus EZ decreased total cholesterol by 0.50 units (SMD = -0.50; 95% CI: -0.80 to -0.19; p = 0.001), LDL-C by 0.57 units (SMD = -0.57; 95% CI: -0.80 to -0.33; p < 0.00001), and triglycerides by 0.85 units (SMD = -0.85; 95% CI: -1.81 to -0.11; p = 0.002). Meanwhile, HDL-C increased by 0.26 units (SMD = 0.26; 95% CI: 0.04 to 0.48; p = 0.02). RSV monotherapy showed a significant risk of elevated liver enzymes (RR 0.36; 95% CI 0.13–0.99; p = 0.05), while combination therapy increased the risk of myalgia (RR 2.17; 95% CI 1.04–4.54; p = 0.04) and gastrointestinal symptoms (RR 2.00; 95% CI 1.01–3.97; p = 0.05). No significant difference in angina pectoris was noted (RR 0.84; 95% CI: 0.39–1.80; p = 0.65). Conclusion: Combination therapy with RSV and EZ effectively improves lipid profiles in high-risk coronary artery disease patients, particularly in reducing total cholesterol, LDL-C, and triglycerides. However, it is associated with a higher risk of gastrointestinal symptoms and myalgia. In contrast, RSV monotherapy is linked to a greater risk of elevated liver enzymes but was also associated with increased HDL-C compared to the combination therapy of RSV + EZ. © The Author(s) 2025.