Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND

Patients undergoing percutaneous coronary intervention (PCI) have a high cardiovascular risk. Current guidelines recommend a ≥50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline. Notably, the recently published 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline continues to support >50% LDL-C reduction while reinstating specific LDL-C targets for very high-risk patients. Statins are widely used to achieve these goals; however, higher-intensity therapy has been associated with adverse effects, including new-onset diabetes mellitus through mechanisms that may include impaired insulin sensitivity, reduced insulin secretion, and altered adipokine signaling. The combination of ezetimibe with a moderate-intensity statin may offer an effective lipid-lowering strategy with fewer metabolic side effects.

OBJECTIVE

This meta-analysis aimed to compare the efficacy and risk of diabetes in patients receiving moderate-intensity statin plus ezetimibe vs high-intensity statin therapy after PCI.

METHODS

A systematic search was conducted in MEDLINE, Scopus, Cochrane Library, and Web of Science through July 18, 2025. Relative risks (RR) with 95% CIs were estimated using random-effects or fixed-effects models. Heterogeneity was assessed with the I² statistic. Analyses were performed in RStudio 4.4.2.

RESULTS

Seven studies, including 121,480 patients, were analyzed. Of these, 26,228 (21.5%) received moderate-intensity statin plus ezetimibe, and 95,252 (78.4%) received high-intensity statins. The moderate-intensity group showed a lower risk of new-onset diabetes requiring medication (RR = 0.83; 95% CI: 0.76-0.91), and all-cause mortality favors moderate-intensity statin plus ezetimibe (RR: 0.89; 95% CI: 0.84-0.95). No significant differences were observed in major adverse cardiovascular events (RR: 0.99; 95% CI: 0.65-1.52) or revascularization (RR: 0.96; 95% CI: 0.83-1.12).

CONCLUSION

This meta-analysis suggests that moderate-intensity statin therapy combined with ezetimibe provides cardiovascular protection equivalent to high-intensity statin therapy, while significantly reducing the risk of new-onset diabetes in patients undergoing PCI.