Dataset Information

Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.

ABSTRACT:

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted inhibitor of the low-density lipoprotein (LDL) receptor and an important regulator of LDL metabolism. Elevated PCSK9 levels have been associated with cardiovascular risk. The purpose of this study was to investigate how ezetimibe and simvastatin, alone and in combination, affect PCSK9 circulating concentrations.

Methods

A single center, randomized, open-label parallel 3-group study in healthy men (mean age 32±9 years, body mass index 25.7±3.2 kg/m(2)) was performed. Each group of 24 subjects was treated for 14 days with either simvastatin 40 mg/d, ezetimibe 10 mg/d, or with both drugs. Multivariate analysis was used to investigate parameters influencing the change in PCSK9 concentrations under treatment.

Results

The baseline plasma PCSK9 concentrations in the total cohort were 52±20 ng/mL with no statistically significant differences between the groups. They were increased by 68±85% by simvastatin (P?=?0.0014), by 10±38% by ezetimibe (P?=?0.51) and by 67±91% by simvastatin plus ezetimibe (P?=?0.0013). The increase in PCSK9 was inversely correlated with baseline PCSK9 concentrations (Spearman's R?=?-0.47, P<0.0001) and with the percent change in LDL cholesterol concentrations (Spearman's R?=?-0.30, P<0.01). In multivariate analyses, only baseline PCSK9 concentrations (??=?-1.68, t?=?-4.04, P<0.0001), percent change in LDL cholesterol from baseline (??=?1.94, t?=?2.52, P?=?0.014), and treatment with simvastatin (P?=?0.016), but not ezetimibe (P?=?0.42), significantly influenced changes in PCSK9 levels. Parameters without effect on PCSK9 concentration changes were age, body mass index, body composition, thyroid function, kidney function, glucose metabolism parameters, adipokines, markers of cholesterol synthesis and absorption, and molecular markers of cholesterol metabolism.

Conclusions

Ezetimibe does not increase circulating PCSK9 concentrations while simvastatin does. When added to simvastatin, ezetimibe does not cause an incremental increase in PCSK9 concentrations. Changes in PCSK9 concentrations are tightly regulated and mainly influenced by baseline PCSK9 levels and changes in LDL cholesterol.

Trial registration

ClinicalTrials.gov NCT00317993.

SUBMITTER: Berthold HK

PROVIDER: S-EPMC3609731 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.

Berthold Heiner K HK Seidah Nabil G NG Benjannet Suzanne S Gouni-Berthold Ioanna I

PloS one 20130327 3

<h4>Background</h4>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted inhibitor of the low-density lipoprotein (LDL) receptor and an important regulator of LDL metabolism. Elevated PCSK9 levels have been associated with cardiovascular risk. The purpose of this study was to investigate how ezetimibe and simvastatin, alone and in combination, affect PCSK9 circulating concentrations.<h4>Methods</h4>A single center, randomized, open-label parallel 3-group study in healthy men (mean ...[more]

PMID: 23544125

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Dataset Information

Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.

Background

Methods

Results

Conclusions

Trial registration

Publications

Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.

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