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Review
. 2025 Jun 10;77(1):58.
doi: 10.1186/s43044-025-00654-y.

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

Arga Setyo Adji  1   2 , Atiyatum Billah  3 , Angga Nugraha  4 , Juliardi Eka Putra Sit  3 , Bryan Gervais de Liyis  5 , Abdillah Maulana Satrio Aji  3 , Ragil Nur Rosyid  6 , Bambang Edi Suwito  7
Affiliations
Review

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

Arga Setyo Adji et al. Egypt Heart J. .

Abstract

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.

Keywords: Coronary artery disease; Efficacy; Ezetimibe; Rosuvastatin; Safety.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of the selection process
Fig. 2
Fig. 2
Risk of bias graph and summary
Fig. 3
Fig. 3
Efficacy outcome of RSV vs RSV plus ezetimibe on lipid profile (TC, LDL-C, HDL-C, TG)
Fig. 4
Fig. 4
Safety outcome of RSV vs RSV plus ezetimibe for A liver enzyme, B gastrointestinal symptoms
Fig. 5
Fig. 5
Safety outcome of RSV vs RSV plus ezetimibe for A myalgia, B angina pectoris
Fig. 6
Fig. 6
Lipid profile subgroup analysis by dose intensity. A Low-Dose RSV (RSV/EZ 2.5–5 mg/10 mg vs. RSV 5–10 mg), B Moderate-Dose RSV (RSV/EZ 10 mg/10 mg vs. RSV 10 mg), and C High-Dose RSV (RSV/EZ 20–40 mg/10 mg vs. RSV 20–40 mg)
Fig. 6
Fig. 6
Lipid profile subgroup analysis by dose intensity. A Low-Dose RSV (RSV/EZ 2.5–5 mg/10 mg vs. RSV 5–10 mg), B Moderate-Dose RSV (RSV/EZ 10 mg/10 mg vs. RSV 10 mg), and C High-Dose RSV (RSV/EZ 20–40 mg/10 mg vs. RSV 20–40 mg)
Fig. 6
Fig. 6
Lipid profile subgroup analysis by dose intensity. A Low-Dose RSV (RSV/EZ 2.5–5 mg/10 mg vs. RSV 5–10 mg), B Moderate-Dose RSV (RSV/EZ 10 mg/10 mg vs. RSV 10 mg), and C High-Dose RSV (RSV/EZ 20–40 mg/10 mg vs. RSV 20–40 mg)
Fig. 7
Fig. 7
Lipid profile subgroup analysis by treatment duration. (A) Short-Term (<6 weeks), (B) Mid-Term (12 weeks), and (C) Long-Term (> 12 weeks)
Fig. 7
Fig. 7
Lipid profile subgroup analysis by treatment duration. (A) Short-Term (<6 weeks), (B) Mid-Term (12 weeks), and (C) Long-Term (> 12 weeks)
Fig. 7
Fig. 7
Lipid profile subgroup analysis by treatment duration. (A) Short-Term (<6 weeks), (B) Mid-Term (12 weeks), and (C) Long-Term (> 12 weeks)
See this image and copyright information in PMC

References

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