16 August 2010
A recent editorial in the Drug and Therapeutics Bulletin questions whether adding ezetimibe to simvastatin▼* is a cost-effective or outcome-based intervention, and whether the increasing monies being spent on ezetimibe (more than £70million in 2009) is a rational use of NHS resources.
*Note: The MHRA has advised that the black triangle (▼) refers to intensive monitoring being requested only when simvastatin is used in children and adolescents (10–17 years), in line with the recently licensed paediatric dosing recommendation.
Prescribers should review, and where appropriate, revise prescribing of ezetimibe to ensure it is in line with NICE guidance.
NICE guidance on lipid modification recommends the use of simvastatin 40mg/day for secondary prevention of cardiovascular (CV) events as well as in primary prevention for adults who have a 20% or greater 10-year risk of developing CV disease. For secondary prevention in patients without acute coronary syndrome (ACS), prescribers should consider increasing the dose of simvastatin to 80mg (or a drug of similar efficacy and acquisition cost) only in patients whose total cholesterol is greater than or equal to 4mmol/L and also whose LDL-cholesterol is greater than or equal to 2mmol/L.
Ezetimibe has a limited role for the treatment of primary hypercholesterolaemia. Addition of ezetimibe to simvastatin 40mg increases the acquisition cost considerably over simvastatin 40mg and has not been demonstrated to deliver better patient-oriented outcomes.
How much does ezetimibe cost the NHS?
Prescribing of ezetimibe has continued to increase steadily over the last five years (see Figure 1). According to the editorial, in 2009 around £73.5 million was spent on ezetimibe in primary care in England, with another £10 million on the combination product simvastatin with ezetimibe (Inegy®).
Figure 1. Prescribing of ezetimibe (not including combination product with simvastatin) in Primary Care in England (NHSBSA © 2010)
Is ezetimibe being used according to NICE guidance?
NICE guidance recommends ezetimibe as an option for the treatment of adults with primary (heterozygous-familial or non-familial) hypercholesterolaemia only in the following circumstances:
- where statins are contraindicated or not tolerated
- in conjunction with a statin where serum total or LDL-cholesterol is not appropriately controlled by initial statin therapy (after appropriate dose titration or because dose titration is limited by intolerance) and when consideration is being given to changing the initial statin therapy to an alternative statin.
When the decision has been made to treat with ezetimibe in conjunction with a statin, ezetimibe should be prescribed on the basis of lowest acquisition cost. Prescribing ezetimibe as a separate tablet with generic simvastatin, rather than using the combination tablet, is a less expensive option.
The NICE implementation costing statement estimated that the primary hypercholesterolaemia guidance would result in an additional 1,400 people receiving ezetimibe monotherapy at an additional annual cost of £260k and that potential increased use of ezetimibe in combination with a statin would be unlikely to have a significant resource impact on the NHS. However, prescribing data suggests that ezetimibe is being used well in excess of that anticipated by NICE following implementation of this guidance.
Why should ezetimibe not be used routinely?
Evidence for efficacy of ezetimibe is based largely on surrogate outcomes (i.e. cholesterol lowering). It is not known whether the reduction in cholesterol achieved with ezetimibe in clinical trials translates into reduced cardiovascular mortality or morbidity, and there is no evidence to suggest its addition to simvastatin 40mg offers any improved tolerability over simvastatin 80mg or alternative NICE-recommended statins.
Concerns have been expressed about a possible link between ezetimibe use and cancer, although the MHRA advised in 2008 that current data were insufficient to draw conclusions. Furthermore, post-marketing adverse event reports did not find any increased risk of cancer with ezetimibe compared with statins, either alone or when taken in combination with simvastatin (see MeReC Rapid Review Blog No. 366).
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