The effect of simvastatin, ezetimibe and their combination on the lipid profile, arterial stiffness and inflammatory markers.
OBJECTIVE
Arterial stiffness and highly sensitive C-reactive protein (hsCRP) serum level predict the risk for cardiovascular events. The most commonly used drugs for lowering cholesterol levels, the statins, also have anti-inflammatory effects and can decrease arterial stiffness. Ezetimibe is the first drug of a new class of cholesterol absorption inhibitors in common use and, to date, its effect on arterial stiffness has not yet been studied. The aim of this study was to compare the effect of simvastatin and ezetimibe, both singly and in combination, on arterial stiffness and hsCRP serum concentration in hypercholesterolemic patients.


METHODS
Forty hypercholesterolemic patients were studied. Group1 comprised previously untreated patients, who received simvastatin at doses of 40 mg/day during the study; group 2 comprised patients previously treated with simvastatin at 40 mg/day, who received simvastatin at 80 mg/day during the study; group 3 consisted of patients previously untreated, who received ezetimibe at doses of 10 mg/day during the study; group 4 comprised patients previously treated with simvastatin at 40 mg/day, who received simvastatin at 40 mg/day and ezetimibe at 10 mg/day during the study. Arterial stiffness expressed as the Augmentation Index (AIx) (assessed by pulse wave analysis), the lipid profile and the hsCRP level were measured at baseline and after 3 months of treatment.


RESULTS
The reduction in low-density lipoprotein (LDL) after treatment was significantly greater in groups 1 and 4 (39.9 and 35.7%) than in groups 2 and 3 (17.7 and 16.9%; p = 0.005). The AIx decreased significantly only in group 1 patients, from 30.2 +/- 8.3% before treatment to 21.6 +/- 6.5% after treatment (p < 0.001). Changes in hsCRP paralleled the changes in AIx, with a significant decrease in patients in group 1 only, from 2.8 +/- 2.5 mg/L before treatment to 1.6 +/- 1.5 mg/L after treatment (p = 0.016).


CONCLUSIONS
Ezetimibe as a monotherapy had no effect on arterial stiffness or hsCRP, while the administration of simvastatin at 40 mg per day improved arterial stiffness and CRP. However, increasing the dose of simvastatin or administering ezetimibe in combination with simvastatin had no beneficial effects on arterial stiffness.
Efrati
S
S
Department of Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel. efratishai@013.net
Averbukh
M
M
Dishy
V
V
Faygenzo
M
M
Friedensohn
L
L
Golik
A
A
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D002097:C-Reactive Protein / Q000187:drug effects* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004548:Elasticity; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D014280:Triglycerides; D002097:C-Reactive Protein; D019821:Simvastatin