Main differences between two highly effective lipid-lowering therapies in subclasses of lipoproteins in patients with acute myocardial infarction

Leticia C S Pinto, Ana P Q Mello, Maria C O Izar, Nagila R T Damasceno, Antonio M F Neto, Carolina N França, Adriano Caixeta, Henrique T Bianco, Rui M S Póvoa, Flavio T Moreira, Amanda S F Bacchin, Francisco A Fonseca, Leticia C S Pinto, Ana P Q Mello, Maria C O Izar, Nagila R T Damasceno, Antonio M F Neto, Carolina N França, Adriano Caixeta, Henrique T Bianco, Rui M S Póvoa, Flavio T Moreira, Amanda S F Bacchin, Francisco A Fonseca

Abstract

Background: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI).

Methods: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test).

Results: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin.

Conclusions: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk.

Trial registration: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.

Conflict of interest statement

Dr. FAH Fonseca declares receiving consulting fees from NovoNordisk, Novartis, and AstraZeneca, lecture fees from Novo Nordisk, Abbott, Ache, Biolab, Libbs, Ely Lilly, Sanofi Aventis, Amgen, and AstraZeneca, and travel support from Amgen, Bayer and NovoNordisk. MC Izar declares receiving consulting fees from Amgen, PTC, Amryt Pharma, Novartis, lecture fees from Amgen, PTC, Libbs, Ache, and travel support from Novo Nordisk and Amgen. The authors have no additional relevant financial or nonfinancial interests to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart. Only patients with a first myocardial infarction (STEMI) undergoing pharmacological thrombolysis during the first 6 h and coronary angiogram followed when necessary by percutaneous coronary intervention in the first 24 h were included. Patients receiving lipid-lowering or immunosuppressive therapy and those with clinical instability and contraindications or known intolerances for the lipid-lowering drugs of the study were excluded. One patient died during the first month after myocardial infarction
Fig. 2
Fig. 2
Delta (final minus initial content in cholesterol) of intermediate-density lipoprotein (IDL) subfractions by lipid-lowering therapies. A The delta of IDL-A (nonatherogenic) was similar after simvastatin plus ezetimibe or rosuvastatin treatment. B The delta of IDL-B plus IDL-C (atherogenic) showed higher effectiveness with simvastin plus ezetimibe than rosuvastatin monotherapy (*P = 0.047, Mann–Whitney U test)
Fig. 3
Fig. 3
Delta (final minus initial cholesterol content) in low-density lipoprotein (LDL) subfractions by lipid-lowering therapies. A The delta of LDL-1 plus LDL-2 (nonatherogenic) was similar after exposure to lipid-lowering therapies. B The delta of atherogenic LDL subfractions (LDL-3 to LDL-7) showed greater reduction by simvastatin plus ezetimibe in comparison with rosuvastatin (*P = 0.043, Mann–Whitney U test)
Fig. 4
Fig. 4
Effects of lipid-lowering therapies on the atherogenic and nonatherogenic subfractions of lipoproteins. Rosuvastatin monotherapy decreased endogenous cholesterol synthesis and augmented both LDL receptor (LDL-R) expression and intestinal cholesterol absorption. The higher expression of LDL-R facilitated the clearance of large and buoyant LDL particles, which had more affinity to LDL-R than small dense particles. Following the use of simvastatin plus ezetimibe, other mechanisms were involved, and the decrease in cholesterol absorption by ezetimibe increased cholesterol synthesis and LDL-R expression. Differences in LDLR expression and lower intestinal cholesterol absorption may contribute to differences in the residual lipoprotein subfraction pattern. Higher effectiveness in the clearance of atherogenic IDL particles was also observed following simvastatin plus ezetimibe therapy compared with rosuvastatin monotherapy

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