Pleiotropic effects with equivalent low-density lipoprotein cholesterol reduction: comparative study between simvastatin and simvastatin/ezetimibe coadministration.
BACKGROUND
Coadministration of any statin with ezetimibe is as effective as using high doses of the same statin in the reduction of low-density lipoprotein cholesterol (LDL-c). There may be other effects called pleiotropics.


OBJECTIVE
To compare the effectiveness of 2 different treatments that obtain equivalent LDL-c reductions (80 mg of simvastatin, once a day and coadministration of 10 mg of simvastatin and 10 mg of ezetimibe, once a day) over endothelial function and inflammation.


METHODS
Twenty-three randomized patients with hypercholesterolemia in a 2 x 2 crossover protocol were studied. Endothelial function was analyzed by ultrasound assessment of endothelial dependent flow-mediated vasodilation of the brachial artery, and inflammation was estimated by high-sensitivity C-reactive protein (hs-CRP).


RESULTS
LDL-c reduction was similar between the 2 treatments with simvastatin/ezetimibe and with simvastatin (P < 0.001); no difference between treatments was found (P = 0.968). Both treatments improved significantly the endothelial function [3.61% with simvastatin/ezetimibe (P = 0.003) and 5.08% with simvastatin (P < 0.001)]; no difference was found between the 2 treatments (P = 0.291). hs-CRP had a 23% reduction with simvastatin/ezetimibe (P = 0.004) and a 30% reduction with simvastatin alone (P = 0.01), with no significant difference between the 2 treatments (P = 0.380).


CONCLUSIONS
The 2 forms of treatment presented similar pleiotropic effects: improvement in endothelial function and decrease in hs-CRP levels.
Araujo
Daniel B
DB
Dyslipidemia Department of Dante Pazzanese, Institute of Cardiology, Sao Paulo, Brazil. dbaraujo@gmail.com
Bertolami
Marcelo C
MC
Ferreira
Waldinai P
WP
Abdalla
Dulcineia S P
DS
Faludi
Andre A
AA
Nakamura
Yara
Y
Bricharello
Liliana P
LP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D002097:C-Reactive Protein; D019821:Simvastatin; D000069438:Ezetimibe