Abstract Body (Do not enter title and authors here): Introduction
Guidelines recommend high-intensity statin treatment for achieving target low-density lipoprotein cholesterol (LDL-C) levels in high-risk patients. Nonetheless, moderate-intensity statin use has been suggested as an alternative in older adult patients due to concerns about adverse effects. Whether a combination approach of a moderate-intensity statin plus ezetimibe is superior to high-intensity statins in older adult patients for hypercholesterolemia is unknown.

Objective
We performed a meta-analysis comparing the combination therapy of moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in older adult patients (≥65 years) with hypercholesterolemia.

Methods
PubMed, Scopus, and Cochrane CENTRAL databases were searched from inception through May 2025 for randomized controlled trials (RCTs) comparing moderate-intensity statin plus ezetimibe versus high-intensity statin in older adults. Outcomes of interest were reduction in LDL-C levels (LDL-C <70 mg/dL or ≥50% reduction in LDL-C), muscle-related adverse effects, new-onset diabetes mellitus (DM), death, and treatment discontinuation due to drug-related adverse effects. Frequentist random-effects meta-analysis was performed to calculate risk ratios (RRs) with 95% confidence intervals (CIs).

Results
Four RCTs with 2453 patients (moderate-intensity statin plus ezetimibe: 1218, 49.6%) were included. The rate of reduction in LDL-C levels (RR 1.2; 95% CI 1.04-1.38; p=0.011; I²=67.2%) was higher with the combination therapy of moderate-intensity statin plus ezetimibe compared with high-intensity statin. Muscle-related adverse effects (RR 0.21; 95% CI 0.07-0.60; p=0.004; I²=0%) and new-onset DM (RR 0.55; 95% CI 0.36-0.86; p=0.008; I²=0%) were lower with moderate-intensity statin plus ezetimibe compared with high-intensity statin. Death and treatment discontinuation were similar between the groups.

Conclusion
In older adult patients, combination therapy of moderate-intensity statin plus ezetimibe demonstrated superior LDL-C reduction and a more favorable safety profile, with lower rates of muscle-related adverse effects and new-onset DM compared with high-intensity statin monotherapy. Moderate-intensity statin plus ezetimibe is a viable treatment option for older adult patients with hypercholesterolemia.