Beyond Cholesterol Lowering: Clinical Caution, Personalization, and Nutritional Integration in Statin Therapy

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Statins are the cornerstone of LDL-C reduction and are highly effective in secondary prevention. However, their benefit in primary prevention among individuals at low-to-moderate cardiovascular risk remains controversial, and long-term adherence is often limited by adverse effects. Methods: This narrative review summarizes current evidence on the clinical effectiveness of statin therapy, with particular attention to the role of nutritional status in modulating statin efficacy, safety, and interpretation of clinical outcomes. Results: In primary prevention among low- to moderate-risk populations, statin therapy often fails to demonstrate a clear reduction in cardiovascular events. Furthermore, 20–30% of patients in secondary or high-risk prevention do not achieve clinically meaningful benefits despite adequate LDL-C lowering. More than half of statin-treated patients discontinue therapy within two years, most commonly because of adverse effects, without a corresponding increase in cardiovascular mortality. Emerging evidence suggests that malnutrition and sarcopenia may significantly influence statin pharmacokinetics and pharmacodynamics, thereby affecting both therapeutic response and susceptibility to adverse events. In addition, statin-induced lipid lowering may alter nutrition-related biomarkers, potentially leading to misclassification or overestimation of malnutrition. Conclusions: Although statins remain effective agents for lowering LDL-C, their prescription should be embedded within an individualized, patient-centered approach. Current guidelines provide a robust methodological framework for statin use; however, their application should be contextualized rather than automatic. Optimal effectiveness is achieved when pharmacological therapy is integrated with dietary patterns, nutritional status, and lifestyle factors. Incorporating nutritional assessment into statin management may improve tolerability, enhance clinical outcomes, and enable more accurate cardiovascular risk stratification beyond standardized cholesterol-lowering strategies.