title: Therapeutic efficacy of PCSK9 monoclonal antibodies in statin-nonresponsive patients with hypercholesterolemia and dyslipidemia: A systematic review and meta-analysis.
abstract: OBJECTIVE
  Heterozygous familial hypercholesterolemia and dyslipidemia are the predominant causes for cardiovascular disease (CVD). Clinical guidelines for lowering CVD risk have advocated that low density lipoprotein-cholesterol (LDL-C) must be reduced. The primary choice of therapy for controlling lipidemia has been statins, which are not completely effective. Proprotein convertase subtilisin/kexin type-9 (PCSK9), which interferes with LDL clearance from circulation, inversely relates to the LDL-C levels. The loss of statin efficacy is likely due to increased circulating PCSK9 and antibody therapy against PCSK9 has been found to be efficacious in lowering LDL-C. In this study, we evaluated the efficacy of PCSK9-mAbs for lowering LDL-C, in statin non-responsive hypercholesterolemia patients.
  
  
  METHODS
  PubMed, EMBASE, Scholar, Web of Science and Scopus databases were searched to identify randomized controlled trials of PCSK9 antibody-statin combination vs statin, published till 2015. Two reviewers independently screened the articles, and a collective decision was reached about the included studies in the metaanalysis. Parameters analyzed: change from baseline in LDL-C, high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); ApoB and ApoA1 levels.
  
  
  RESULTS
  A total of 12 studies with 4909 patients were selected. Overall, add-on therapy with PCSK9-mAb to the ongoing statin therapy was found to achieve greater reduction in LDL-C, ApoB, TC, compared to statin therapy. There were no major treatment emergent adverse effects due to PCSK9-mAb therapy.
  
  
  CONCLUSIONS
  In adult patients with heterozygous familial hypercholesterolemia and dyslipidemia, PCSK9-mAb therapy in combination with statins was able to achieve the goal of lowering LDL-C.
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Wan
authors: W
authors: Peng
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China. Electronic address: fuqiang@medmail.com.cn.
authors: Fu
authors: F
authors: Qiang
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Wei
authors: W
authors: Peng
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Zhang
authors: Z
authors: Qian
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Zhu
authors: Z
authors: Ke
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Lu
authors: L
authors: Yi
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Zhong
authors: Z
authors: Jian
authors: Department of Cardiology, Xuzhou Hospital Affiliated East South University School of Medicine, Xuzhou Cardiovascular Disease Institute, 199 Jiefang Road, Xuzhou 221009, PR China.
authors: Qiu
authors: Q
authors: Chongrong
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006952:Hyperlipoproteinemia Type III / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D054539:Medication Therapy Management; D000071449:Proprotein Convertase 9 / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Dyslipidemia; Hypercholesterolemia; LDL-Cholesterol; PCSK9; Statins