Abstract 13757: Niacin Reverses Increased Plasma PCSK9 Induced by Statin and Fibrate Therapy: A Novel Mechanism for Further LDL Reduction

Abstract

Background PCSK9 is a secreted glycoprotein that reduces active LDL receptor (LDLR), thereby raising low density lipoprotein cholesterol (LDL-C) levels. Both statins and fibrates have been shown to increase plasma PCSK9 levels. The effect of niacin on plasma PCSK9 levels is unknown.

Objective To investigate the added effect of niacin on plasma PCSK9 levels in dyslipidemic subjects on statin and/or fibrate therapy.

Methods We compared the additive effects of niacin on plasma PCSK9 in two studies. Study 1 was a placebo-controlled trial (n = 71) in which subjects with carotid atherosclerosis and dyslipidemia were randomized to simvastatin 20 mg+2 grams extended-release (ER) niacin versus simvastatin monotherapy with 20 or 80 mg. Plasma PCSK9 levels were assessed at baseline and month 12. Study 2 was an open-label study (n=19) in which patients with dyslipidemia on atorvastatin 10 mg daily were treated with 8 weeks of fenofibric acid (150 mg) followed by 10 weeks of 2 grams ER niacin. Plasma PCSK9 levels were measured at baseline, 8 weeks of fenofibric acid and 10 weeks of niacin therapy

Results In study 1, compared to baseline, 80 mg simvastatin increased plasma PCSK9 levels from 364 to 505 ng/ml (38.7% increase; p <0.01), whereas there was no significant change on 20 mg simvastatin. In contrast, the statin+niacin combination decreased plasma PCSK9 levels from 399 to 331 ng/ml (17% reduction; p <0.05). In study 2, fenofibric acid+atorvastatin increased PCSK9 level from 415 ng/ml to 504 ng/ml (21 % increase; p < 0.01). In contrast, adding niacin to this combination lowered plasma PCSK9 level from 504 to 402 ng/ml (20% decrease; p<0.01)

Conclusion Both of our studies demonstrate a novel PCSK9 lowering effect of niacin: niacin lowers plasma PCSK9, and this effect was potent enough to reverse statin and fibrate induced increases in PCSK9. The LDL-lowering effect of niacin may be due in part to reduction in PCSK9. Further studies are warranted to test this and confirm our findings.