Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Abstract

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 randomeffects 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 3 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.

Fenofibrate improves renal function by amelioration of NOX‐4, IL‐18, and p53 expression in an experimental model of diabetic nephropathy

“…This finding is consistent with previous studies suggesting pleiotropic effects of fibrates besides their putative triglyceride‐lowering properties . Fibrates are known to possess antioxidant effects and also ameliorate some glycemic and thrombotic factors, reduce uric acid, increase adiponectin, and enhance endothelial function …”

Lipid Parameters are Independently Associated with Cardio–Ankle Vascular Index (CAVI) in Healthy Japanese Subjects

“…Fibrate is a widely used class of lipid-regulating agents that affects lipoprotein metabolism, attenuates postprandial lipemia and reduces TG-rich lipoprotein 60 , 61 ) . Fibrate was reported to improve endothelial function as assessed by flow-mediated dilation 62 , 63 ) . In addition, Satoh et al 64 ) .…”

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“…Fenofibrate may also increase tetrahydrobiopterin levels (BH 4 ), an essential cofactor for eNOS and ultimately NO production [22] , [23] . With increases in NO bioavailability, comes improved vascular reactivity in vivo [24] , [25] . Although studies examining changes in endothelial function with fenofibrate in humans have been relegated to the brachial artery, changes in brachial endothelial-dependent flow-mediated dilation correlate with changes in coronary [26] and pulmonary vascular endothelial reactivity [27] , suggesting the fenofibrate may have favorable systemic endothelial effects, particularly in vascular beds impacted by COVID-19 [28] , [29] , [30] , [31] .…”