Plasma PCSK9 is increased by fenofibrate and atorvastatin in a non-additive fashion in diabetic patients.
OBJECTIVE
Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by fenofibrate and statins. Here, we determined how standard dose of statin and combined therapy with fenofibrate modulate PCSK9.


METHODS
Randomized, open-label cross-over study investigating the effect of fenofibrate (160 mg), atorvastatin (10 mg), and combination of both in patients with type 2 diabetes mellitus and atherogenic dyslipidemia. After the single administration of atorvastatin and fenofibrate for 6 weeks, patients received both for another 6 weeks. PCSK9, lipids and lipoproteins levels were determined at day 1, weeks 6, 9 and 12.


RESULTS
Upon 6 weeks of treatment, atorvastatin decreased LDL-cholesterol by 30% (p<0.001) and fenofibrate decreased triglyceride level by 31% (p<0.01) and increased HDL-cholesterol by 13% (p<0.05). Combination did not show further benefit. Atorvastatin increased PCSK9 by 24% at day 1 and by 14% at week 6 (p < or = 0.01). Fenofibrate increased PCSK9 by 26% at week 6 (p < or = 0.01), but had no effect at day 1. Three weeks of combination therapy increased PCSK9 by 42%, 6 weeks by 19% (p < or = 0.01). PCSK9 changes were not different between treatments over 6-week periods.


CONCLUSIONS
Fenofibrate and atorvastatin increased circulating PCSK9 in diabetic patients, with no additive effect after 6 weeks of combined therapy.
Costet
P
P
INSERM, U915, Nantes F-44000, France. philippe.costet@univ-nantes.fr
Hoffmann
M M
MM
Cariou
B
B
Guyomarc'h Delasalle
B
B
Konrad
T
T
Winkler
K
K
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005602:France; D005858:Germany; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011758:Pyrroles / Q000627:therapeutic use*; D012697:Serine Endopeptidases / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D011345:Fenofibrate