Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials.
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.
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.
Amirhossein
A
Sahebkar
Geriatric Department, Campus Bio-Medico University and Teaching Hospital, Rome, Italy. Electronic address: r.giua@unicampus.it.
Renato
R
Giua
Geriatric Department, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.
Claudio
C
Pedone
Department of Public Health and Primary Care, School of Public Health, Imperial College London, UK.
Kausik K
KK
Ray
Department of Public Health and Primary Care, School of Public Health, Imperial College London, UK.
Antonio J
AJ
Vallejo-Vaz
Geriatric Department, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.
Luisa
L
Costanzo
D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D058607:Fibric Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012039:Regional Blood Flow; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D014665:Vasodilator Agents
Cardiovascular risk; Endothelial function; Flow-mediated dilation; Meta-analysis; Pharmacology