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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial
Heiner K Berthold1, Manfredi Rizzo2, Nadine Spenrath3
1Department of Internal Medicine and Geriatrics, Bielefeld Evangelical Hospital (EvKB), Bielefeld, Germany.
Insights
Simvastatin favorably altered HDL subclasses in healthy men, increasing large HDL and decreasing intermediate HDL. Ezetimibe did not show these effects, with simvastatin
Area of Science:
- Lipid metabolism and cardiovascular disease research.
- Pharmacological effects on lipoprotein subclasses.
Background:
- Investigating lipid-lowering drugs' impact on HDL subclasses has yielded inconsistent findings.
- This study addresses the need for clarity on how specific drugs affect HDL composition.
Purpose of the Study:
- To assess the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution in healthy men.
- To determine if simvastatin or ezetimibe induces more favorable changes in HDL subclasses.
Main Methods:
- A 14-day randomized, open-label study in 72 healthy men.
- Participants received ezetimibe, simvastatin, or a combination.
- HDL subclasses were analyzed using polyacrylamide gel-tube electrophoresis before and after treatment.
Main Results:
- Simvastatin treatment (alone or combined) significantly increased large HDL by ~3.9% and decreased intermediate HDL by ~3.5% compared to ezetimibe.
- These changes were partially attributed to simvastatin's greater LDL-cholesterol-lowering effect.
- Ezetimibe monotherapy did not significantly alter HDL subclass distribution.
Conclusions:
- Simvastatin demonstrates beneficial effects on HDL subclass composition in healthy individuals.
- Ezetimibe does not appear to induce similar favorable shifts in HDL subclasses.
- The enhanced HDL profile with simvastatin may be partly explained by its potent LDL-cholesterol reduction.
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.
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