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



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).



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.



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.
Faculty of Pharmacy in Hradec Kralove, Department of Biological and Medical Sciences, Charles University, Hradec Kralove, Czech Republic.
Eva
E
Dolezelova
Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA.
Evan
E
Stein
Centre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Center for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, Pavia, Italy.|Molecular Medicine Laboratory, University of Pavia, Pavia, Italy.
Giuseppe
0000-0003-3573-4760
G
Derosa
Centre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|PhD School in Experimental Medicine, University of Pavia, Pavia, Italy.
Pamela
P
Maffioli
Faculty of Pharmacy in Hradec Kralove, Department of Biological and Medical Sciences, Charles University, Hradec Kralove, Czech Republic.
Petr
P
Nachtigal
Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|School of Medicine, University of Western Australia, Perth, WA, Australia.
Amirhossein
A
Sahebkar
D052242:Adiponectin / Q000097:blood; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D000069438:Ezetimibe / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
C499918:ADIPOQ protein, human; D052242:Adiponectin; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069438:Ezetimibe
adipose tissue; cytokine; ezetimibe; pleiotropic; statin; tumour necrosis factor α