Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction

Abstract

For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Figure 1

Evaluation of clinical results for the infarcted patients under investigation. G1: Patients randomized to the rosuvastatin group at the first day of myocardial infarction (D1); G2: Patients treated by rosuvastatin after 30 days (D30); G3: Patients randomized to the simvastatin + ezetimibe group at the first day of myocardial infarction (D1); G4: Patients treated by simvastatin plus ezetimibe after 30 days (D30). Total cholesterol (TC), low density lipoprotein—cholesterol (LDL-C), high density lipoprotein—cholesterol (HDL-C) and triglycerides (TG*). Figure was created in Minitab 17.0 (Minitab Statistical Software; URL: https://www.minitab.com/pt-br/)) and Microsoft PowerPoint 2013 (URL: https://www.microsoft.com/pt-br/microsoft-powerpoint-2013).

Figure 2

Evaluation of lipid classes for the infarcted patients under evaluation itemized by class (a) and by group (b). CE cholesterol ester, Cer ceramides, FA free fat acids, LPC lysophosphatidylcholine, LPE lysophosphatidylethanolamine, PC phosphatidyl choline, PE phosphatidylethanolamine, SM sphingomyelin, TG triacylglycerides; group labels as in Fig. 1. Figure was created in Minitab 17.0 (Minitab Statistical Software; URL: https://www.minitab.com/pt-br/) and Microsoft PowerPoint 2013 (URL: https://www.microsoft.com/pt-br/microsoft-powerpoint-2013). ±Mean Value.

Figure 3

Pearson’s correlation of lipid classes concentrations and clinical parameters. (a) for rosuvastatin treatment at D1 (G1), (b) for simvastatin plus ezetimibe treatment at D1 (G3), (c) for rosuvastatin treatment (G2) at D30, and (d) for simvastatin plus ezetimibe treatment at D30 (G4). Figure was created in R 3.6.3 (The R Project for Statistical Computing; https://www.r-project.org/packages: corrplot, Hmisc, RColorBrewer, Cairo).

Figure 4

OPLS-DA scores plot (PC1 vs PC2) of all infarcted patients in the four groups considered. G1: Patients randomized to the rosuvastatin group at first day after myocardial infarction (D1); G2: Patients treated by rosuvastatin after 30 days of treatment (D30); G3: Patients randomized to the simvastatin plus ezetimibe group at the first day after myocardial infarction (D1); G4: Patients treated by simvastatin plus ezetimibe after 30 days (D30). Figure was created in SIMCA 16 (Statistical Software Package, Umetrics, Sweden; URL: http://umetrics.com/product/simca).

Figure 5

Discriminant lipids from multivariate (VIP > 1) and univariate analysis (repeated measures ANOVA). (a) % change of metabolites considering the temporal treatment effect (*metabolite statistically significant are highlighted with black borders); (b) % of change of metabolites considering the lipid-lowering therapy effect (*metabolite statistically significant are highlighted with black border); (c) Venn Diagram considering lipid-lowering therapy; (d) Venn Diagram considering temporal treatment effect. Figure was created in Microsoft Excel 2013 (URL: https://www.microsoft.com/pt-br/microsoft-excel-2013) and Microsoft PowerPoint 2013 (URL: https://www.microsoft.com/pt-br/microsoft-powerpoint-2013).