Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy.
It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
L M
LM
Camargo
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
C N
CN
França
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
M C
MC
Izar
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
H T
HT
Bianco
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
L S
LS
Lins
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
S P
SP
Barbosa
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
L F
LF
Pinheiro
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
F A H
FA
Fonseca
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001241:Aspirin / Q000627:therapeutic use; D001384:Azetidines / Q000494:pharmacology*; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy*; D004338:Drug Combinations; D066026:Endothelial Progenitor Cells / Q000187:drug effects*; D000069438:Ezetimibe; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D000077144:Clopidogrel; D019821:Simvastatin; D000069438:Ezetimibe; D013988:Ticlopidine; D001241:Aspirin