title: Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia.
abstract: Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a +23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9.
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: avkhera@mgh.harvard.edu.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Khera
authors.affiliation: Department of Medicine, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania; Cardiovascular Institute, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Arman
authors.initials: A
authors.lastname: Qamar
authors.affiliation: Department of Medicine, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania; Cardiovascular Institute, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Department of Medicine, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania; Cardiovascular Institute, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Dunbar
authors.affiliation: Department of Medicine, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania; Cardiovascular Institute, Smilow Center for Translational Research, Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D009525:Niacin / Q000008:administration & dosage*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood* / Q000187:drug effects; D012697:Serine Endopeptidases / Q000097:blood* / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009525:Niacin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D011345:Fenofibrate