A systematic review and meta-analysis of randomized controlled trials (RCTs) published in the Journal of Clinical Lipidology assessed the relationship between remnant cholesterol (RC) reduction and cardiovascular (CV) outcomes in adults receiving lipid-lowering therapies. Searches of Cochrane Central and Embase identified RCTs enrolling ≥1000 participants with a planned duration of ≥2 years, comparing cholesterol- or triglyceride-lowering therapies with placebo, usual care, or alternative lipid-lowering agents.

Data extraction and methodological quality assessment were conducted independently by two reviewers. Meta-analysis and meta-regression techniques were applied to evaluate associations between lipid parameter changes and clinical outcomes. Inclusion criteria comprised large-scale RCTs meeting duration and comparator requirements, while specific exclusion criteria were not detailed in the abstract.

A total of 43 RCTs met eligibility criteria. Most studies exhibited some degree of bias, and overall certainty of evidence was rated as moderate. Meta-analysis demonstrated absolute risk reductions in treatment groups compared with controls of 0.4% (95% confidence interval [CI] 0.1%–0.6%) for all-cause mortality, 1.3% (95% CI 1.1%–1.6%) for myocardial infarction (MI), and 0.4% (95% CI 0.2%–0.6%) for stroke. 

However, meta-regression analysis found no significant association between RC reduction and any clinical outcome. In contrast, reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were associated with improved outcomes.

RC reduction was not associated with measurable CV benefit in this analysis. Differences from observational findings may reflect methodological and exposure-related variations.