Abstract
Objective. Statin treatment alone has been demonstrated to significantly increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The effect of policosanol combined with statin on PCSK9 is unknown. Methods. Protocol I: 26 patients with atherosclerosis were randomly assigned to receive either atorvastatin 20 mg/d or policosanol 20 mg/d + atorvastatin 20 mg/d for 8 weeks. Protocol II: 15 healthy volunteers were randomly assigned to either policosanol 20 mg/d or a control group for 12 weeks. Serum levels of PCSK9 were determined at day 0 and the end of each protocol. Results. Protocol I: atorvastatin 20 mg/d significantly increased serum PCSK9 level by 39.4% (256 ± 84 ng/mL versus 357 ± 101 ng/mL, P = 0.002). However, policosanol 20 mg/d + atorvastatin 20 mg/d increased serum PCSK9 level by only 17.4% without statistical significance (264 ± 60 ng/mL versus 310 ± 86 ng/mL, P = 0.184). Protocol II: there was a trend toward decreasing serum PCSK9 levels in the policosanol group (289 ± 71 ng/mL versus 235 ± 46 ng/mL, P = 0.069). Conclusion. Policosanol combined with statin attenuated the statin-induced increase in serum PCSK9 levels. This finding indicates that policosanol might have a modest effect of lowering serum PCSK9 levels.
Highlights
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein in low-density lipoprotein cholesterol (LDLC) metabolism by virtue of its pivotal role in the degradation of the LDL receptor [1]
The interactions of statins with PCSK9 are of great interest, because statins are the predominant therapeutic agents used to decrease LDLC and cardiovascular adverse events and because statin exposure might increase the concentration of serum PCSK9 [2]
After 8 weeks of treatment in Protocol I, atorvastatin 20 mg/d significantly increased serum PCSK9 levels by 39.4%, while policosanol 20 mg/d + atorvastatin 20 mg/d increased serum PCSK9 levels only by 17.4% and this difference did not reach a statistical significance
Summary
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein in low-density lipoprotein cholesterol (LDLC) metabolism by virtue of its pivotal role in the degradation of the LDL receptor [1]. Several small studies have found that moderate- to highdose statins could increase serum PCSK9 levels [3, 4]. An increased PCSK9 level largely negates further statin-induced increases in the hepatic LDL-C receptor level. This may be a major reason behind statins’ “6%” rule in its lipid-lowering effect [5, 6]. Policosanol is a natural lipid-modulating drug that slowly and modestly lowers LDL-C, is well tolerated, and has an excellent safety profile. Our previous study on policosanol showed that it does not increase PCSK9 as much as statins (unpublished data). We aimed to explore a potentially useful combination lipid-modulating strategy that would not increase PCSK9 levels. This study was designed to examine the efficacy of a combination of policosanol 20 mg and atorvastatin 20 mg in patients with atherosclerosis in a small, randomized, controlled trial
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