Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects

• Published in: Atherosclerosis Vol. 233; no. 1; pp. 319 - 325
• Main Authors: Mangili, Otavio Celeste, Moron Gagliardi, Ana C, Mangili, Leonardo Celeste, Mesquita, Carlos H, Machado Cesar, Luiz A, Tanaka, Akira, Schaefer, Ernst J, Maranhão, Raul C, Santos, Raul D
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2014
• Subjects: Aged; ApoB-48; Azetidines - administration & dosage; Cardiovascular; Cholesterol Esters - metabolism; Chylomicron Remnants - metabolism; Chylomicrons; Chylomicrons - blood; Chylomicrons - metabolism; Coronary Disease - blood; Coronary Disease - drug therapy; Drug Therapy, Combination; Emulsions; Ezetimibe; Female; Humans; Kinetics; Male; Middle Aged; Simvastatin; Simvastatin - administration & dosage; Triglyceride-rich lipoproteins; Triglycerides - blood; Triolein - metabolism; ApoB-48; Chylomicrons; Triglyceride-rich lipoproteins; Emulsions; Simvastatin; Ezetimibe
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2013.12.008

Abstract Objective Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. Methods 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with14 C-CE and3 H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. Results The14 CE-FCR in group 1 were 0.005 ± 0.004, 0.011 ± 0.008 and 0.018 ± 0.005 min−1 and in group 2 were 0.004 ± 0.003, 0.011 ± 0.008 and 0.019 ± 0.007 min−1 respectively at baseline, after 6 and 12 weeks ( p  < 0.05 vs. baseline, and 6 vs. 12 weeks). The3 H-TG-FCR in group 1 were 0.017 ± 0.011, 0.024 ± 0.011 and 0.042 ± 0.013 min−1 and in group 2 were 0.016 ± 0.009, 0.022 ± 0.009 and 0.037 ± 0.012 min−1 at baseline, after 6 and 12 weeks ( p  < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. Conclusion Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.