Changes in lipoproteins associated with lipid-lowering and antiplatelet strategies in patients with acute myocardial infarction

PLoS One. 2022 Aug 30;17(8):e0273292. doi: 10.1371/journal.pone.0273292. eCollection 2022.

Abstract

Background: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles.

Methods: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions.

Results: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size.

Conclusions: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents* / adverse effects
  • Clopidogrel
  • Ezetimibe / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lipoproteins
  • Myocardial Infarction* / chemically induced
  • Myocardial Infarction* / drug therapy
  • Prospective Studies
  • Rosuvastatin Calcium / therapeutic use
  • Scattering, Small Angle
  • Simvastatin / therapeutic use
  • Ticagrelor
  • X-Ray Diffraction

Substances

  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins
  • Rosuvastatin Calcium
  • Clopidogrel
  • Simvastatin
  • Ezetimibe
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT02428374

Grants and funding

FF received financial support by the Research Foundation of the State of Sao Paulo - FAPESP (grant # 2012/51692-7) and by an investigator-initiated grant from AstraZeneca (ESR 14-10726). AF received grant by the National Institute of Science and Technology Complex Fluids (INCT-FCX) (grant # 428793/2016-9) and by FAPESP Thematic Project # 2016/24531-3 and 2018/07340-5. the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.