Title:Impact of Statin or Fibrate Therapy on Homocysteine
Concentrations: A Systematic Review and Meta-analysis
Volume: 31
Issue: 14
Author(s): Abolfazl Akbari, Muhammad Islampanah, Hadise Arhaminiya, Mohammad Mahdi Alvandi Fard, Tannaz Jamialahmadi and Amirhossein Sahebkar*
Affiliation:
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Statin, fibrate, homocysteine, atherosclerosis, dyslipidemia, lipid-lowering drugs.
Abstract:
Introduction: Statins and fibrates are two lipid-lowering drugs used in patients
with dyslipidemia. This systematic review and meta-analysis were conducted to determine
the magnitude of the effect of statin and fibrate therapy on serum homocysteine
levels.
Methods: A search was undertaken of the PubMed, Scopus, Web of Science, Embase,
and Google Scholar electronic databases up to 15 July 2022. Primary endpoints focused
on plasma homocysteine levels. Data were quantitatively analyzed using fixed or random-
effect models, as appropriate. Subgroup analyses were conducted based on the
drugs and hydrophilic-lipophilic balance of statins.
Results: After screening 1134 papers, 52 studies with a total of 20651 participants were
included in the meta-analysis. The analysis showed a significant decrease in plasma homocysteine
levels after statin therapy (WMD: -1.388 μmol/L, 95% CI: [-2.184, -0.592], p
= 0.001; I2 = 95%). However, fibrate therapy significantly increased plasma homocysteine
levels (WMD: 3.459 μmol/L, 95% CI: [2.849, 4.069], p < 0.001; I2 = 98%). The effect
of atorvastatin and simvastatin depended on the dose and duration of treatment (atorvastatin
[coefficient: 0.075 [0.0132, 0.137]; p = 0.017, coefficient: 0.103 [0.004, 0.202];
p = 0.040, respectively] and simvastatin [coefficient: -0.047 [-0.063, -0.031]; p < 0.001,
coefficient: 0.046 [0.016, 0.078]; p = 0.004]), whereas the effect of fenofibrate persisted
over time (coefficient: 0.007 [-0.011, 0.026]; p = 0.442) and was not altered by a change
in dosage (coefficient: -0.004 [-0.031, 0.024]; p = 0.798). In addition, the greater homocysteine-
lowering effect of statins was associated with higher baseline plasma homocysteine
concentrations (coefficient: -0.224 [-0.340, -0.109]; p < 0.001).
Conclusion: Fibrates significantly increased homocysteine levels, whereas statins significantly
decreased them.
