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FOCUS ON LIPIDS
MANAGEMENT Amber Briggs,
Section Advisor
Niacin better than ezetimibe when added to statin therapy
Key point: Based on 14-month data from 208 patients,
the addition of extended release niacin (Niaspan—Abbott) to
long-term statin monotherapy resulted in a significant reduction in
carotid intima-media thickness (CIMT), whereas the addition of ezetimibe
(Zetia—Merck; Schering-Plough) to statin therapy resulted in no
significant changes in CIMT, despite greater reductions in low-density
lipoprotein (LDL) levels compared with niacin.
Finer points: Results of the ARBITER 6-HALTS
(Arterial Biology for the Investigation of the Treatment Effects of
Reducing Cholesterol 6: HDL and LDL Treatment Strategies in
Atherosclerosis) trial were presented at the 2009 American Heart
Association Scientific Sessions by principal investigator Allen Taylor,
MD, FAHA, of the Washington Hospital Center and published simultaneously
online in the New England Journal of Medicine. The trial was a
randomized, open-label study that compared the effects of extended
release niacin, dosed to a target of 2,000 mg at bedtime (n = 97), with
ezetimibe 10 mg daily (n = 111) on CIMT in patients with coronary heart
disease or a coronary heart disease risk equivalent. These drugs were
given to patients with LDL levels less than 100 mg/dL and high-density
lipoprotein (HDL) levels less than 50 mg/dL for men or 55 mg/dL for
women who were on long-term statin therapy; 95% of the patients had
received simvastatin or atorvastatin (Lipitor—Pfizer) at a mean
daily dose of 42 mg for approximately 6 years.
The trial was terminated early on the basis of efficacy because the
change in CIMT at 14 months was significantly better with niacin therapy
(–0.0142 mm) compared with ezetimibe (–0.0007 mm, P
= 0.003). In addition, major cardiovascular events occurred more
frequently in the ezetfimibe group compared with the niacin group (5%
vs. 1%, P = 0.04), although the difference represents only
seven patients. When assessing lipid parameters, LDL levels were reduced
to a greater extent with ezetimibe compared with niacin (–17.6
mg/dL vs. –10.0 mg/dL, P = 0.01); however, a posthoc
analysis revealed a “paradoxical” increase in CIMT in
patients in the ezetimibe group who had greater reductions in LDL. HDL
levels were only increased in the niacin group (7.5 mg/dL vs. –2.8
mg/dL, P < 0.001). Flushing of the skin was reported by more
than one-third of patients (36%) in the niacin group.
What you need to know: In an attempt to explain the
results, Taylor and colleagues wrote, “We hypothesize that the
seemingly paradoxical association of greater ezetimibe-induced reduction
of LDL cholesterol level with a greater increase in carotid intima-media
thickness is biologically plausible if it is associated with the
unintended disruption of reverse cholesterol transport.” Other
experts have commented on the limitations of ARBITER 6-HALTS, including
the use of a controversial surrogate marker such as CIMT for coronary
atherosclerosis, the fact that the majority of patients received maximum
doses of statin therapy before the addition of a second lipid-lowering
agent, the trial’s premature discontinuation, and its small sample
size. Nonetheless, ARBITER 6-HALTS is another negative trial for
ezetimibe and places this agent further down the list for add-on agents.
Until data from larger outcomes trials with ezetimibe are available,
agents such as niacin appear to be a better second-line treatment option
added to a maximum tolerated dose of a statin. Currently, ezetimibe
approved by FDA as monotherapy or in combination with other
lipid-lowering therapies to reduce total cholesterol and LDL.
What your patients need to know: Educate patients
that recent data suggest that the addition of niacin to statin therapy
is preferred over the addition of ezetimibe. If patients begin using
niacin, counsel them on ways to minimize flushing, such as taking the
drug after meals or taking aspirin 325 mg 30 minutes before the
niacin.
Sources:
Related resources on www.pharmacist.com
Beth Farnstrom (bfarnstrom@aphanet.org)
Posted December 14, 2009
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