Key result
In patients with acute myocardial infarction, simvastatin/ezetimibe with ticagrelor or clopidogrel reduced LDL oxidation, while rosuvastatin with ticagrelor uniquely increased LDL particle size.
Why the study?
Despite lipid-lowering and antiplatelet therapy, residual lipoprotein patterns remain relevant to long-term outcomes, prompting evaluation of how combined acute myocardial infarction therapies affect LDL particle quality.
Does the combination of different antiplatelet (ticagrelor vs clopidogrel) and lipid-lowering (rosuvastatin vs simvastatin/ezetimibe) therapies improve the quality of LDL particles in patients with acute myocardial infarction?
RCT (n=123)
Open-label (with blinded endpoints)
1:1 and 1:1 (two-by-two factorial design)
No
Does the combination of different antiplatelet (ticagrelor vs clopidogrel) and lipid-lowering (rosuvastatin vs simvastatin/ezetimibe) therapies improve the quality of LDL particles in patients with acute myocardial infarction?
In patients with acute myocardial infarction, the combination of ticagrelor with either rosuvastatin or simvastatin/ezetimibe is associated with improved LDL particle quality and reduced atherogenicity.
Answers are grounded in this paper and cite their sources.
No immediate clinical implications for regimen selection; leaves open whether LDL changes affect prognosis in acute MI.
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.
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Lotfollahi et al. (2022) conducted an RCT in Acute myocardial infarction (STEMI) (n=123). Ticagrelor or clopidogrel plus rosuvastatin or simvastatin/ezetimibe vs. Active comparators (2x2 factorial design) was evaluated on Quality of low-density lipoprotein (LDL) particles (oxidative state, size, and subfractions). In patients with acute myocardial infarction, simvastatin/ezetimibe with ticagrelor or clopidogrel reduced LDL oxidation, while rosuvastatin with ticagrelor uniquely increased LDL particle size.
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