Sahebkar Amirhossein, Giua Renato, Pedone Claudio, Ray Kausik K, Vallejo-Vaz Antonio J, Costanzo Luisa
Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Geriatric Department, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.
Pharmacol Res. 2016 Sep;111:163-179. doi: 10.1016/j.phrs.2016.06.011. Epub 2016 Jun 15.
Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A random-effects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p<0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p<0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p<0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.
肱动脉血流介导的舒张功能（FMD）反映了内皮依赖性血管舒张功能；由于它与冠状动脉内皮功能相关，其降低可预测心血管事件。多项研究探讨了贝特类药物治疗对内皮功能的潜在影响，但临床研究结果并不完全一致。我们旨在对随机安慰剂对照试验进行荟萃分析，以阐明贝特类药物治疗是否能改善内皮功能。我们在PubMed-Medline、SCOPUS、Web of Science和谷歌学术数据库中进行了系统检索，以确定随机安慰剂对照试验，这些试验研究了贝特类药物对通过FMD评估的内皮功能的影响。荟萃分析采用随机效应模型和通用逆方差法。使用标准方法进行敏感性分析、偏倚风险评估和发表偏倚评估。采用随机效应荟萃回归评估治疗持续时间对估计效应大小的影响。15项试验共556名受试者符合纳入标准。贝特类药物治疗显著改善了FMD（加权平均差[WMD]：1.64%，95%CI：1.15，2.13，p<0.001），并且在治疗持续时间≤8周（WMD：1.35%，95%CI：0.85，1.86，p<0.001）和>8周（WMD：2.55%，95%CI：1.21，3.89，p<0.001）的两个亚组中均得到证实。当根据贝特类药物类型进行分层分析时，非诺贝特组观察到显著效果，而吉非贝齐组未观察到，尽管两个亚组之间的差异不显著。对有硝酸酯介导的舒张功能（NMD）数据的试验进行荟萃分析，未发现贝特类药物治疗后NMD有显著变化。该荟萃分析结果表明，即使在短期治疗过程中，贝特类药物也可能对内皮功能产生有益影响。
