Efficacy of High-Intensity Versus Moderate-Intensity Statins in Primary Prevention of Cardiovascular Disease: A Meta-Analysis

Abstract

Background: Statins are commonly prescribed for the primary prevention of cardiovascular disease (CVD). However, there is ongoing debate about the most appropriate intensity of statin therapy for individuals without established CVD. Although high-intensity statins produce greater reductions in low-density lipoprotein cholesterol (LDL-C), it remains uncertain whether this biochemical benefit leads to meaningful improvements in cardiovascular outcomes when compared with moderate-intensity therapy.

Objective: To evaluate and compare the efficacy and safety of high-intensity versus moderate-intensity statin therapy in adults receiving statins for primary prevention of cardiovascular disease.

Methods: A systematic review and meta-analysis were performed in accordance with PRISMA guidelines. Randomised controlled trials and observational studies published between 2020 and 2025 were identified through structured database searches. Studies that directly or indirectly compared high-intensity and moderate-intensity statin therapy in primary prevention populations were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for major adverse cardiovascular events (MACE), myocardial infarction, stroke, all-cause mortality, and statin-associated adverse effects. Differences in LDL-C reduction were assessed using mean differences, and random-effects models were applied to account for heterogeneity.

Results: A total of fifteen studies met the inclusion criteria. High-intensity statin therapy resulted in significantly greater reductions in LDL-C compared with moderate-intensity therapy (mean difference −12.4%, 95% CI −10.1 to −14.7; p < 0.001). Despite this, no statistically significant difference was observed in the incidence of major adverse cardiovascular events between the two treatment strategies (RR 0.97, 95% CI 0.91–1.04; p = 0.42). High-intensity statin use was associated with a higher risk of statin-associated muscle symptoms (RR 1.32, 95% CI 1.18–1.48; p < 0.001) and increased rates of treatment discontinuation.

Conclusion: In individuals undergoing primary prevention, high-intensity statins achieve greater LDL-C lowering but do not provide a clear additional benefit in reducing cardiovascular events compared with moderate-intensity therapy. Given the higher frequency of adverse effects and reduced tolerability associated with high-intensity regimens, moderate-intensity statins—particularly when used in combination with ezetimibe—offer an effective and more sustainable option for many patients. Clinical decision-making should therefore focus on individual cardiovascular risk, long-term adherence, and treatment tolerability rather than statin intensity alone.