Dolezelova Eva, Stein Evan, Derosa Giuseppe, Maffioli Pamela, Nachtigal Petr, Sahebkar Amirhossein
Faculty of Pharmacy in Hradec Kralove, Department of Biological and Medical Sciences, Charles University, Hradec Kralove, Czech Republic.
Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA.
Br J Clin Pharmacol. 2017 Jul;83(7):1380-1396. doi: 10.1111/bcp.13250. Epub 2017 Mar 10.
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.
已知他汀类药物会影响脂肪因子的状态,而脂肪因子在心脏代谢疾病的病理生理学中起关键作用。由于目前尚不清楚依折麦布作为他汀类药物治疗的附加药物对他汀类药物对血浆脂肪因子水平影响的作用,本研究的目的是通过对对照试验的荟萃分析来对此进行调查。
进行了系统评价,随后在PubMed、Medline、SCOPUS、科学网和谷歌学术数据库中进行文献检索。使用固定效应或随机效应模型(基于研究间异质性水平)和通用逆方差加权法进行定量数据合成。效应大小以标准化均数差(SMD)和95%置信区间(CI)表示。
对23项对照试验的荟萃分析表明,在他汀类药物治疗基础上加用依折麦布对脂联素(SMD 0.34,95%CI -0.28,0.96;P = 0.288)、瘦素(SMD -0.75,95%CI:-2.35,0.85;P = 0.360)、纤溶酶原激活物抑制剂1(SMD -1.06,95%CI:-2.81,0.69;P = 0.236)和白细胞介素6(SMD 0.30,95%CI:-0.08,0.67;P = 0.124)的血浆浓度均无显著影响。然而,依折麦布/他汀联合治疗可使肿瘤坏死因子α(TNF-α)的血浆浓度显著降低(SMD -0.48,95%CI -0.87,-0.08;P = 0.018)。
结果表明,与他汀类药物单药治疗相比,在他汀类药物治疗基础上加用依折麦布可增强降低TNF-α的效果。鉴于TNF-α在代谢紊乱发病机制中的新作用,需要进一步研究以揭示这种降低TNF-α效果的转化相关性。