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Ezetimibe offers extra protection against secondary heart attacks and strokes  

Treating heart attack patients with the lipid-lowering drug ezetimibe as well as a statin lowered their risk of another cardiovascular event, research published in NEJM shows.

The study – providing the first long-term outcomes data on ezetimibe – found the combination was associated with a two percentage point reduction in the rate of a composite outcome that included cardiovascular death, MI and stroke, when compared with treatment with a statin alone.

Over 18,000 patients were involved, all of whom had recently had an acute coronary syndrome and had ‘normal’ LDL cholesterol levels - above 50 mg/dL (1.3 mmol/L), but no higher than 100 mg/dL (2.6 mmol/L) if they were already on lipid-lowering therapy or 125 mg/dL (3.2 mmol/L) if not. The participants were randomly assigned to a combination of simvastatin (40mg) and ezetimibe (20mg) daily, or simvastatin (40mg) and placebo.

Over the six-year study period, the patients who took ezetimibe achieved lower cholesterol levels, with a median LDL cholesterol of 53.7 mg/dL (1.4 mmol/L) compared with 69.5 mg/dL (1.8 mmol/L) in the statin-only group.

The rate of the primary endpoint (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalisation, coronary revascularisation or nonfatal stroke) at seven years of follow-up was 32.7% in the ezetimibe group compared with 34.7% in the simvastatin only group – equating to a significant 6% relative reduction in risk.

The researchers concluded: ‘The addition of ezetimibe to statin therapy in stable patients who had had an acute coronary syndrome and who had LDL cholesterol levels within guideline recommendations further lowered the risk of cardiovascular events.

‘The event reduction was consistent with the predicted effects seen with statins, even in the range of low LDL cholesterol levels in this trial, and no offsetting adverse events or toxic effects were observed.’

The research provides long-awaited evidence to support NICE recommendations on ezetimibe - its use was first recommended in 2007 lipid modification guidelines, a decision that was questioned at the time and came under further scrutiny when an interim study found that the addition of the drug did not reduce progression of atherosclerosis any further than with statin monotherapy.

NEJM 2015; available online 3 June


Readers' comments (16)

  • If you prescribe ezetimibe in our area medicines management make you feel like a child killer,I think there is a national target not to use it,I just love it when managers are wrong footed by science

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  • Ivan Benett

    It took a population of 18,000 and 7 years to show a statistical significant difference. Whether this represents a clinical difference is debatable. NNT therefore enormous. Don't fall for this Pharma con!

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  • Well said Ivan. A 2% reduction in 5 clinical end points detected after 7 yrs in 18,000 patients. In 7 years the treatment of most of these 5 end points have changed and so have other areas of clinical practice. have they corrected for all those changes as well?
    Lets see this "science" repeated by anther group or lets have an independent organisation analyse all the data.
    Paul C

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  • I was going to mention the NNT but Ivan beat me to it.

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  • Vinci Ho

    Interesting American Study but reality is patients with ACS will be discharged with more potent statin e.g. Atorvastatin 80mg in UK. Simvastatin 40mg is certainly less potent . In their description of study protocol , the authors wrote this ;
    ......For patients in either study group who had LDL cholesterol levels higher than 79 mg per deciliter (2.0 mmol per liter) on two consecutive measurements, the simvastatin dose was increased to 80 mg in a double-blind manner. In June 2011, in accordance with Food and Drug Administration guidance for limiting new prescriptions of 80 mg of simvastatin, patients were no longer eligible for an increased dose of simvastatin to 80 mg, and any patient who had been receiving the 80-mg dose for less than 1 year had the dose reduced to 40 mg.23 If an LDL cholesterol measurement on the new regimen was confirmed to be higher than 100 mg per deciliter, the study drug could be discontinued and more potent therapy initiated. The study continued until each patient had been followed for a minimum of 2.5 years and until the target number of events (5250) was reached. Five amendments to the protocol were implemented during the course of the study, including an increase in the sample size.

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  • Samuel Lewis

    the scandal is that Ezetemibe has been marketed since last century, and only now is there a sliver of evidence ( 32.7% versus 34.7% after 8 years ) that adding it to Statin might be a marginal improvement over statin alone.

    For heaven sake - many GPs on this forum haven't accepted the long-proven power of statin yet !!

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  • Samuel Lewis

    sorry ... I meant 6 year study period.

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  • Samuel Lewis

    Quick maths..
    ACS is a very high risk starting group, and the 34.7% events outcome confirms this.

    34.7% event rate on statin leads me to infer on event rate of 51% if there had been a placebo group, since we know that statins cut cvd events by one-third.

    thus over 6 years an ARR of 17% with statin (NNT per annum= 36 ) , compared to an extra 2% ARR by adding ezetimibe ( NNT per annum= 300) . How many of the GPs who have argued against statin in risk category 10-20 % still prescribe ezetimibe ??

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  • thanks re NTT but as always ; NNH ??
    so hard to explain to patients -lay people -
    and even colleagues and do not even get me started on NICE or Jezza. H$$t......and his larger family

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  • Russell Thorpe

    I use it for pts with high Tgs and increased risk of pancreatitis. Not relevant to this study or discussion. Its use will be one of the "triggers" discussed by the CCG at our practice visit in a few days.

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