Diapositiva 1

1
EZETIMIBE, A SELECTIVE INHIBITOR OF
CHOLESTEROL ABSORPTION,

AS A NEW
STRATEGY FOR TREATMENT OF HYPERCHOLESTEROLEMIA
SECONDARY TO ANTIRETROVIRAL THERAPY E. NEGREDO1,
C. REY-JOLY2, J. PUIG1, A. BONJOCH1, J. MOLTÓ1,
A. BLANCO1, B. CLOTET1. 1 Lluita contra la SIDA
and IrsiCaixa Foundations 2 Internal Medicine
Department. Germans Trias i Pujol University
Hospital, Universitat Autònoma de Barcelona,
Badalona, Barcelona, Spain.
BACKGROUND Ezetimibe (EZB), the first selective
inhibitor of cholesterol absorption at intestinal
level, reduces its absorption at duodenal level
by approximately 50, attaining reductions of LDL
cholesterol of 20. With any of the statins,
reductions of LDL cholesterol reaches up to 50.
Studies in HIV-infected subjects with dyslipemia
frequently show only partial responses to
statins.
DESIGN and OBJECTIVE This is a
prospective, open-label study to 24 weeks of
follow-up designed - To assess
the short term efficacy and safety of the
addition of EZB to pravastatin in HIV-infected
patients with LDL-cholesterol 130 mg/dL despite
pravastatin. - To assess the pharmacokinetic
interactions between EZB and antiretrovirals.
METHODS
Follow-up BL and Weeks 6, 12 and 24
Total-cholesterol Liver enzymes
LDL-cholesterol CK HDL-cholesterol
Pharmacokinetic study BL and after 12 weeks
of EZB AUC12h, Cmax, Cmin of NNRTIs
or PIs
Participants HIV-1 infected patients with
stable (? 3 months) HAART LDL ?130 md/dL despite
the use of pravastatin, 20 mg/day Triglycerides
lt350 mg/dL to avoid interferences to calculate LDL
Baseline visit (BL) To continued pravastatin,
20 mg/day, and the same HAART to start EZB,
10 mg/day, at dinner time. Recommendations The
maintenance of the usual diet and of grade of
exercise throughout the follow-up.
Reasons for study discontinuation changes on
diet or exercise changes on HAART, ? grade II
adverse event, EZB discontinuation for any reason.
RESULTS
Total, LDL- and HDL-cholesterol considering all
patients and depending on ARV
BL characteristics
Pharmacokinetic study (n 7 patients)
Change from baseline at wks 6 and 24
Pre - Ezetimibe Post - Ezetimibe
Men / Women, n 15 / 7
Mean age, years 43
BMI 25,7
Smokers, 10
Antiretroviral treatment PI NNRTI No treatment 10 8 1
LDL - cholesterol
Total cholesterol
HDL - cholesterol
LPV
mg/dL
of change from baseline
NVP
p ns between pre- and post-ezetimibe Cmax and
AUC12h for lopinavir (LPV, n6) and nevirapine
(NVP, n1).
plt0.05 between baseline and weeks 6, 12 and 24
for all paramenters
CONCLUSIONS
At the short term, the addition of EZB to low
doses of pravastatin improved significantly lipid
parameters in patients with poor responses to
pravastatin alone. The lack of interaction with
the cytochrome CYP3A4 and its good tolerance mean
that EZB can be given jointly with
antiretrovirals without the risk of
pharmacokinetic interactions or greater toxicity.
Contact e-mail enegredo_at_ns.hugtip.scs.es