Introduction: Statins, also known as 3-Hydroxy-3-Methylglutaryl Co-A (HMG-CoA) reductase inhibitors, are lipid-lowering agents that are central in preventing or reducing the complications of atherosclerotic cardiovascular disease. Because statins have anti-inflammatory properties, there is considerable interest in their therapeutic potential in other chronic inflammatory conditions. We aim to identify the statin with the greatest ability to reduce systemic inflammation, independent of the underlying disease entity.
Methods and analysis: We aim to conduct a comprehensive search of published and peer-reviewed randomized controlled clinical trials (RCT), with at least one intervention arm of an FDA or EMA-licensed statin and a minimum treatment duration of 12 weeks. Our objective is to investigate the effect of statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin) on lipid profile, particularly, cholesterol low-density lipoprotein (LDL-C) and inflammation markers such as hsCRP, CRP, TNF-α, IL-1β, IL-6, IL-8, sCD14, or sCD16 in adults, published in the last 20 years (between January 1999 and December 2019). We aim to identify the most potent statin to reduce systemic inflammation and optimal dosing. The following databases will be searched: Medline, Scopus, Web of Science, and Cochrane Library of Systematic Reviews. The risk of bias of included studies will be assessed by Cochrane Risk of Bias tool and Quality Assessment Tool for Quantitative Studies. The quality of studies will be assessed, to show uncertainty, by the Jadad score. If sufficient evidence is identified, a meta-analysis will be conducted with risk ratios or odds ratios with 95% confidence intervals (CI) in addition to mean differences.
Ethics and dissemination: Ethics approval is not required as no primary data will be collected. Results will be presented at conferences and published in a peer-review journal.
PROSPERO registration number: Pending

Strengths and limitations of this study
• This study will include randomized controlled clinical trials to determine the most effective statin on the combined reduction of lipid profile and inflammatory biomarkers.
• High-quality clinical trials will be reviewed accurately to generate reliable evidence.
• This study will be conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines.
• Variation of statin doses among included studies will likely produce heterogeneity that will subsequently reduce the sample size of the meta-analysis.