Dataset Information

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

ABSTRACT:

Context and objective

Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution.

Design and participants

A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n?=?24), simvastatin (40 mg/day, n?=?24) or their combination (n?=?24) for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition.

Results

Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05) and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01) in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering.

Conclusions

In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin.

Trial registration

ClinicalTrials.gov NCT00317993.

SUBMITTER: Berthold HK

PROVIDER: S-EPMC3963857 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

Berthold Heiner K HK Rizzo Manfredi M Spenrath Nadine N Montalto Giuseppe G Krone Wilhelm W Gouni-Berthold Ioanna I

PloS one 20140324 3

<h4>Context and objective</h4>Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution.<h4>Design and participants</h4>A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg ...[more]

PMID: 24662777

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Project description:AimsLipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.Methods and resultsCardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.ConclusionBaseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

Dataset Information

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

Context and objective

Design and participants

Results

Conclusions

Trial registration

Publications

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

Similar Datasets

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