title: Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta-analysis of clinical trials.
abstract: OBJECTIVE
  To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta-analysis of clinical trials.
  
  
  METHODS
  A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using an unrestricted maximum likelihood method to evaluate the association between statin-induced elevation of plasma PCSK9 concentrations with duration of treatment and magnitude of LDL cholesterol reduction.
  
  
  RESULTS
  A total of 15 clinical trials examining the effects of statin therapy on plasma PCSK9 levels were included. Meta-analysis of data from single-arm statin treatment arms [weighted mean difference (WMD) 40.72 ng/ml, 95% confidence interval (CI) 34.79, 46.65; p < 0.001] and randomized placebo-controlled trials (WMD 22.98 ng/ml, 95% CI 17.95, 28.01; p < 0.001) showed a significant increase in plasma PCSK9 concentrations after statin therapy, irrespective of the type of statin administered in either of the analyses (single-arm or randomized placebo-controlled trial). There was no significant elevation of plasma PCSK9 levels with statin/ezetimibe combination therapy compared with statin monotherapy (WMD 23.14 ng/ml, 95% CI -1.97, 48.25; p = 0.071); however, removal of one study in the meta-analysis yielded a significant result in the sensitivity analysis (WMD 31.41 ng/ml, 95% CI 7.86, 54.97; p = 0.009).
  
  
  CONCLUSIONS
  This meta-analysis suggests that statin therapy causes a significant increase in plasma PCSK9 concentrations.
authors.affiliation: Biotechnology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.|Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico.
authors.forename: L E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Guerrero-Romero
authors.affiliation: Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University Townsville, Townsville, Queensland, Australia.|Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Golledge
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D000069438:Ezetimibe / Q000494:pharmacology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012044:Regression Analysis; D012697:Serine Endopeptidases / Q000097:blood*; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe
keywords: PCSK9; meta-analysis; statin