Atherosclerosis not slowed by adding ezetimibe to simvastatin
Clinicians treating patients with high cholesterol should return to statins first line — this was the message
from a panel of experts at the American College of Cardiology annual scientific session held in Chicago this week. The panel had been convened after the ENHANCE study
showed that adding ezetimibe to simvastatin produced no additional
benefits over simvastatin alone for progression of atherosclerosis.
Speaking for the expert panel, Harlan Krumholz, of Yale University, New
Haven, Connecticut, said: “We know statins lower risk and need
to go back to what works and stay with the evidence.”
The next step, he added, should be to use niacin, resins and fibrates. “We
know they’re not tolerated as well, but at least there’s
evidence they’re worth trying.”
In the ENHANCE study, 720 patients with familial hypercholesterolaemia
were randomised to 80mg of simvastatin with either placebo or 10mg of
ezetimibe. Patients underwent ultrasonography to assess intima media
wall thickness of carotid and femoral arteries at baseline and then at
six, 12, 18 and 24 months.
Results showed the mean change in carotid artery intima media thickness
was 0.0058±0.0037mm in the simvastatin-only group and 0.0111±0.0038mm
in the combination simvastatin plus ezetimibe group (P=0.29). The combination
arm did, however, show reduced levels of low-density lipoprotein cholesterol,
triglyceride and C-reactive protein levels.
Presenting the results, John Kastelein, of the Academic Medical Centre,
Amsterdam, suggested three possible explanations for lack of benefit — the
technique for measuring arterial thickness might not be accurate enough,
certain lipid-independent effects of statins, such as the pleiotrophic
effect, may not be shared by ezetimibe, and due to the study population’s
intensity of pre-treatment with statins, it might be difficult to show
any additional benefit.
In the UK, ezetimibe accounts for less than 5 per cent of lipid-lowering
medicines, compared with 16 per cent in the US, said Helen Williams,
specialist cardiac pharmacist at King’s College Hospital, London.
“This
study emphasises the importance of optimising statin doses in the first
instance, but, after that, ezetimibe represents a valid option for adding
in. One positive thing to come out of ENHANCE is that combining ezetimibe
with a statin is safe and tolerable, which is not the case with fibrates,
resin and niacin.”
Ms Williams added that because the trial was a surrogate endpoint study
conducted in a small number of patients, the relevance of the results
to clinical practice is questionable.
The ENHANCE results are published
online in The New England Journal of
Medicine. |
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