title: Efficacy and safety of mipomersen in treatment of dyslipidemia: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in people at risk for cardiovascular diseases. Mipomersen inhibits apolipoprotein B-100 (apoB) synthesis and causes reduction in LDL-C by reducing apoB.
  
  
  OBJECTIVE
  We aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia.
  
  
  METHODS
  We searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size.
  
  
  RESULTS
  We identified 8 randomized controlled trials (n = 462). Mipomersen compared with placebo significantly reduced LDL-C by 32.37% (95% confidence interval, 25.55-39.18; P < .00001), total cholesterol by 24.18% (18.54-29.83; P < .00001), very low-density lipoprotein cholesterol by 21.59% (9.16-34.02; P = .0007), non-high-density lipoprotein cholesterol (HDL-C) by 30.83% (23.92-37.74; P < .00001), and triglycerides by 36.26% (22-50.54; P < .00001). It also significantly reduced apoB, lipoprotein(a), and apolipoprotein A1. However, mipomersen did not significantly change HDL-C levels. In safety analysis, mipomersen compared with placebo increased the risks of injection-site reaction (risk ratio, 2.05; 95% confidence interval, 1.39-3.04; P = .0003), flu-like symptoms (1.63; 1.22-2.17; P = .0008), alanine aminotransferase ≥3X upper limit of normal (4.44; 1.67-11.86; P = .003), and hepatic steatosis (3.85, 1.39-10.67; P = .01). The risks of alanine aminotransferase ≥10X upper limit of normal did not reach statistical significance (1.57; 0.32-7.6, P = .58).
  
  
  CONCLUSIONS
  Mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo.
authors.affiliation: Department of Hospital Medicine, LRGHealthcare, Laconia, NH, USA. Electronic address: rpanta@lrgh.org.
authors.forename: Raju
authors.initials: R
authors.lastname: Panta
authors.affiliation: Department of Hospital Medicine, LRGHealthcare, Laconia, NH, USA.
authors.forename: Khagendra
authors.initials: K
authors.lastname: Dahal
authors.affiliation: Department of Hospital Medicine, LRGHealthcare, Laconia, NH, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kunwar
mesh_terms: D053299:Apolipoprotein B-100 / Q000097:blood; D054316:Biomarkers, Pharmacological / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D009841:Oligonucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011973:Receptors, LDL / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D053299:Apolipoprotein B-100; D054316:Biomarkers, Pharmacological; D008076:Cholesterol, HDL; D009841:Oligonucleotides; D011973:Receptors, LDL; D014280:Triglycerides; C524142:mipomersen
keywords: Apolipoprotein B; Apolipoprotein B synthesis inhibitor; Familial dyslipidemia; HDL cholesterol; Hepatic steatosis; Hyperlipidemia; LDL cholesterol; Mipomersen; Non-HDL cholesterol; Total cholesterol