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2015 ; 36
(1
): 39-48
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Anacetrapib reduces progression of atherosclerosis, mainly by reducing
non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects
of atorvastatin
#MMPMID25142968
Kühnast S
; van der Tuin SJ
; van der Hoorn JW
; van Klinken JB
; Simic B
; Pieterman E
; Havekes LM
; Landmesser U
; Lüscher TF
; Willems van Dijk K
; Rensen PC
; Jukema JW
; Princen HM
Eur Heart J
2015[Jan]; 36
(1
): 39-48
PMID25142968
show ga
BACKGROUND: The residual risk that remains after statin treatment supports the
addition of other LDL-C-lowering agents and has stimulated the search for
secondary treatment targets. Epidemiological studies propose HDL-C as a possible
candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters
from atheroprotective HDL to atherogenic (V)LDL. The CETP inhibitor anacetrapib
decreases (V)LDL-C by ?15-40% and increases HDL-C by ?40-140% in clinical trials.
We evaluated the effects of a broad dose range of anacetrapib on atherosclerosis
and HDL function, and examined possible additive/synergistic effects of
anacetrapib on top of atorvastatin in APOE*3Leiden.CETP mice. METHODS AND
RESULTS: Mice were fed a diet without or with ascending dosages of anacetrapib
(0.03; 0.3; 3; 30 mg/kg/day), atorvastatin (2.4 mg/kg/day) alone or in
combination with anacetrapib (0.3 mg/kg/day) for 21 weeks. Anacetrapib
dose-dependently reduced CETP activity (-59 to -100%, P < 0.001), thereby
decreasing non-HDL-C (-24 to -45%, P < 0.001) and increasing HDL-C (+30 to +86%,
P < 0.001). Anacetrapib dose-dependently reduced the atherosclerotic lesion area
(-41 to -92%, P < 0.01) and severity, increased plaque stability index and added
to the effects of atorvastatin by further decreasing lesion size (-95%, P <
0.001) and severity. Analysis of covariance showed that both anacetrapib (P <
0.05) and non-HDL-C (P < 0.001), but not HDL-C (P = 0.76), independently
determined lesion size. CONCLUSION: Anacetrapib dose-dependently reduces
atherosclerosis, and adds to the anti-atherogenic effects of atorvastatin, which
is mainly ascribed to a reduction in non-HDL-C. In addition, anacetrapib improves
lesion stability.
|Animals
[MESH]
|Anticholesteremic Agents/*pharmacology
[MESH]
|Atherosclerosis/*prevention & control
[MESH]
|Atorvastatin
[MESH]
|Cholesterol Ester Transfer Proteins/metabolism
[MESH]