title: Raloxifene Lowers Plasma Lipoprotein(a) Concentrations: a Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.
abstract: OBJECTIVE
  Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein and an independent risk factor for atherosclerotic cardiovascular disease. We investigated the effects of raloxifene, selective estrogen receptor modulator, on circulating Lp(a) levels in postmenopausal women using a systematic review and meta-analysis of randomized controlled trials (RCTs).
  
  
  METHODS
  To identify relevant studies, electronic databases (PUBMED, Scopus, Web of Science, and Google Scholar) were searched by up to May 2015 to find controlled trials exploring the effects of oral raloxifene treatment on plasma Lp(a) levels in postmenopausal women. A random-effects model and generic inverse variance method were used for quantitative data synthesis.
  
  
  RESULTS
  Overall, seven eligible RCTs with ten treatment arms were included in this meta-analysis. Meta-analysis suggested a significant reduction of Lp(a) levels after treatment with raloxifene (standardized mean difference (SMD) -0.42; 95% CI -0.65, -0.19; p < 0.001), which may be considered as a medium effect size. When the studies were categorized according to the administered dose, there was a significant effect in both subsets of studies with administered doses ≤60 mg/day (SMD -0.43; 95% CI -0.73, -0.13; p = 0.004) and >60 mg/day (SMD -0.36; 95% CI -0.68, -0.05; p = 0.025). No significant association between the changes in plasma concentrations of Lp(a) with dose and baseline Lp(a) levels was found in the random-effects meta-regression analysis. However, a significant inverse association was observed between the Lp(a)-lowering effect of raloxifene and duration of treatment (p = 0.001).
  
  
  CONCLUSIONS
  Results of the present meta-analysis showed a reduction in plasma Lp(a) concentrations of postmenopausal women with oral raloxifene treatment.
authors.affiliation: Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Ferretti
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bacchetti
authors.affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.affiliation: Department of Internal Medicine, University Hospital Center Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12, Zagreb, Croatia.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Reiner
authors.affiliation: Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir.|Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir.|School of Medicine, University of Western Australia, Perth, Iran. sahebkara@mums.ac.ir.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017270:Lipoprotein(a); D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride
keywords: Cardiovascular diseases; Estrogen receptor modulators; Lipoprotein(a); Menopause; Raloxifene