Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials

Ann Med. 2018 Sep;50(6):485-493. doi: 10.1080/07853890.2018.1495338. Epub 2018 Sep 7.

Abstract

Aims: To assess the effect of fibrates on circulating cystatin C levels.

Material and methods: Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels.

Results: This meta-analysis of data from nine published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; eight studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p < .001; I2 = 82.66%). When the analysis was restricted to randomized controlled trials (four studies comprising six treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p < .001; I2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate and not with other fibrates.

Conclusions: The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events. Key message Fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.

Keywords: Fibrates; cystatin C; fenofibrate.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / antagonists & inhibitors
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic
  • Cystatin C / blood*
  • Cystatin C / metabolism
  • Fibric Acids / pharmacology
  • Fibric Acids / therapeutic use*
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy*
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use*
  • PPAR alpha / agonists
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • Cystatin C
  • Fibric Acids
  • Hypolipidemic Agents
  • PPAR alpha
  • PPARA protein, human