What is this about?
The results (login required) of the ENHANCE Study have found no significant difference between the combination of ezetimibe▼ and simvastatin compared to simvastatin alone in patients with heterozygous familial hypercholesterolemia.
The results of this study were due to be presented later this year at a meeting of the American College of Cardiology but many of the results are already available in an attempt to “end speculation about the results of the study” according to the manufacturers.
What happened in this study?
The study recruited 720 patients with heterozygous familial hypercholesterolemia and randomised them to treatment with ezetimibe▼10mg and simvastatin 80mg or simvastatin 80mg alone for a period of 2 years. The primary end point was the mean change in the intima media thickness as measured at three sites in the carotid arteries.
There was no statistical difference in the primary outcome, the components of the primary outcome or the secondary imaging end points. Although the trial was not powered to assess it, there was also no significant differences in cardiovascular events either. Additional long-term cardiovascular outcome studies with ezetimibe▼ are on going but are not due for completion until 2011.
The NICE technology appraisal on ezetimibe▼ in hypercholesterolaemia states that ezetimibe▼ may be used in combination with a statin in limited circumstances in adults with primary hypercholesterolaemia. This option should be considered only where statin therapy has not appropriately controlled serum total or LDL cholesterol despite appropriate statin dose titration (or in people who cannot tolerate higher doses of a statin) and consideration is being given to changing from the initial statin used to an alternative statin.
Despite ENHANCE patients having heterozygous familial hypercholesterolemia, the results should, in our view, strengthen support for a very cautious approach to using ezetimibe▼ as discussed in a previous NPC blog. There are difficulties in doing research which will unequivocally demonstrate that ezetimibe▼ will reduce cardiovascular events because comparison with placebo will usually be unethical. Publication of the ENHANCE results appears to have been complicated by attempts to amend the primary endpoint after the trial had ended, and the results released only after intervention by the chairman of a US Congressional Committee. This raises concerns that clinicians have been, and perhaps still are, unable to assess for themselves some of the relevant research on ezetimibe▼.
For most patients who require a drug to lower their cholesterol, simvastatin 40mg remains first line and monotherapy with atorvastatin remains a suitable second line in patients who fail to reach the national cholesterol targets of 5mmol/L for total cholesterol or 3mmol/L for low-density lipoprotein (LDL-C).The great majority of concordant patients will achieve a good reduction in their total cholesterol, and meet the Quality and Outcomes Framework (QOF) standard of 5 mmol/L total cholesterol or less, on simvastatin 40 mg a day alone.
Action: Clinicians should be aware of this negative study, which did not assess whether patients with heterozygous familial hypercholesterolemia would live longer or better if ezetimibe▼ is added to simvastatin
More information on lipid management can be found on the lipids section of NPC.
Acknowledgement: This blog first appeared on Matt Robinson’s Prescribing Advice for GPs and is used with permission.