Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis

Aims: Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials. Methods: A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI). Results: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI –0.28, 0.96; P = 0.288), leptin (SMD –0.75, 95% CI: –2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD –1.06, 95% CI: –2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: –0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD –0.48, 95% CI –0.87, −0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy. Conclusions: The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.