Background: Statins are the gold standard in the treatment of dyslipidemia, significantly reducing the risk of cardiovascular disease. Objective: To systematically review the efficacy and safety of Moderate-intensity Rosuvastatin Plus Ezetimibe compared with High-intensity Rosuvastatin in treating Composite Cardiovascular Events. Methods: PubMed, Embase, Cochrane Library, CINAHL, Web of Science, China Knowledge Network, China Biological Literature Database, Wan Fang Database, and Weipu Database were searched to retrieve randomized controlled trials assessing the safety and efficacy of the two therapies from the time of construction to December 2023. The Jadad scale assessment tool was used to evaluate the quality of the included literature, and Review Manager 5.4 software was used for meta-analysis. The heterogeneity of outcomes was estimated by the I² test, where we applied risk ratios (RR) and 95% confidence intervals (CI) to assess dichotomous outcomes and mean difference (MD) and 95% CI to present continuous outcomes. We used funnel plots to assess study publication bias and sensitivity analysis was used to address significant clinical heterogeneity. Results: The meta-analysis described 21 RCTs involving 24592 participants. The findings indicated that moderate-intensity statin combination therapy improved low-density lipoprotein cholesterol (LDL-C) (MD -8.06, 95% CI [-9.48, -6.64] p < 0.05), total cholesterol (TG) (MD -5.66, 95% CI [-8.51, -2.82] p < 0.05), and non-high-density lipoprotein cholesterol (non-HDL-C) (MD -17.04, 95% CI [-29.55, -4.54] p < 0.05) to a greater extent and superior in achieving LDL-C <70 (RR1.26, 95% CI [1.22, 1.29] p < 0.05) and LDL-C <55 (RR1.66, 95% CI [1.56, 1.77] p < 0.05) ratios and in the incidence of adverse events than the high-intensity Rosuvastatin monotherapy group. However, there was no statistical difference between the two in improving HDL-C, total cholesterol (TC), and preventing long-term composite adverse cardiovascular events (ACE). Funnel plots indicated publication bias. Sensitivity analysis suggested instability in long-term composite cardiovascular events, HDL-C, and TC results. Conclusions: Moderate-intensity statin plus ezetimibe with combination therapy had better efficacy and safety than high-intensity statins. Future validation is needed with more long-term high-quality large samples.

To systematically evaluate the effect of ABCG2 c.421 C > A (rs2231142) single nucleotide polymorphism (SNP) on the lipid-modulating efficacy of rosuvastatin (RST). Searches were conducted using the Wan Fang database, Web of Science, Embase, PubMed, Cochrane Library, and China Journal Full Text Database. The time frame for the search was from the database's creation to September 1, 2024. The RevMan 5.4 software was used to conduct a meta-analysis after the literature was filtered based on the inclusion and exclusion criteria, and pertinent data was extracted following methodological quality evaluation. A total of 7 studies, including 1347 patients, were included. Meta-analysis showed that in a dominant model of inheritance, RST had a significant effect on low-density lipoprotein cholesterol (LDL-C) [MD = -7.23, 95% CI (-8.71, -5.75), P < 0.05], total cholesterol (TC) [MD = -7.15, 95% CI (-8.71, -5.75), P < 0.05], and triglyceride (TG) [MD = -7.34, 95% CI (-10.88, -3.80), P < 0.05] in patients harboring an A allele decreased significantly more than CC, but there was no significant difference in the change of high-density lipoprotein cholesterol (HDL-C) [MD = -2.22, 95% CI (-19.87, 15.43), P = 0.81]. The results of the sensitivity analysis suggested that all outcome indicators were stable. However, this study's small sample size may be heterogeneous, and more large-sample, multi-center studies are needed for future validation. The ABCG2 c.421 C > A (rs2231142) SNP significantly affected the lipid-modulating efficacy of RST, especially the down-regulation of LDL-C, TC, and TG.

Objective: To investigate the effects of SLCO1B1, apolipoprotein E (APOE) and ABCG2 gene polymorphisms on the lipid-modulating efficacy of rosuvastatin. Methods: Systematic searches were conducted in PubMed, Cochrane Library, Embase, Web of Science, PharmGKB, CNKI, VIP, and Wanfang databases (from database establishment to 1 March 2025). Studies on the correlation between SLCO1B1, APOE, ABCG2 gene polymorphisms and the lipid-modulating efficacy of rosuvastatin were collected, and meta-analysis was performed using RevMan 5.4 software. Results: A total of 16 studies involving 6167 patients were included, covering APOE (p.C130R/rs429358, p.R176C/rs741), SLCO1B1 (p.V174A/rs4149056, p.N130D/rs2306283), and ABCG2 (p.Q141K/rs2231142) genes. The results showed that SLCO1B1 [AG+GG vs. AA, mean difference = −4.36, 95% confidence interval (CI): −7.92 to −0.80, P = 0.02], APOE (E2 vs. E3, mean difference = −5.58, 95% CI: −8.04 to −2.51, P < 0.00001] and ABCG2 (CA+AA vs. CC, mean difference = −7.07, 95% CI: −9.47 to −4.68, P < 0.00001) genotypes all significantly affected statin-induced low-density lipoprotein cholesterol (LDL-C) reduction; patients with ABCG2 CA+AA genotype had statistically significant differences in total cholesterol level changes (mean difference = −7.15, 95% CI: −8.78 to −5.53) and triglyceride level changes (mean difference = −7.37, 95% CI: −10.91 to −3.83) (both P < 0.05). Conclusion: The lipid-lowering efficacy of rosuvastatin (especially the reduction of LDL-C level) is significantly affected by the polymorphisms of SLCO1B1 (c.388A>G), ApoE (c.388T>C, c.526C>T) and ABCG2 (c.421C>A) genes.