Abstract
BACKGROUND: Currently, there are various lipid-lowering therapies in clinical practice, and the emergence of PCSK9 inhibitors has undoubtedly added a valuable tool to lipid-lowering strategies. However, existing studies lack comparisons between different PCSK9 inhibitors and between the outcomes of using PCSK9 inhibitors alone versus in combination with statins. Therefore, this study aims to explore the efficacy and safety of different lipid-lowering regimens, aiming to determine the optimal lipid-lowering regimen. METHODS: We searched PubMed/Medline and the Cochrane Library of Clinical Trials for related articles published up to October 2024. A network meta-analysis was applied including studies comparing PCSK9 inhibitors with statins or ezetimibe that have MACE outcomes. The efficacy endpoint was MACE, and the safety endpoints were new-onset diabetes and neurocognitive impairment. RESULTS: We included a total of 29 studies, comprising 68,686 patients. Compared to oral lipid-lowering drugs, PCSK9 inhibitors combined with statins significantly reduced the incidence of MACE. While, PCSK9 inhibitors alone did not significantly reduce the risk of MACE. CONCLUSION: For patients requiring intensive lipid lowering, the combination of PCSK9 inhibitors with statins provides the greatest clinical benefit. While, for patients with moderate to low risk who need only single-drug therapy, statins are generally preferred over PCSK9 inhibitors considering various factors.