The Pharmaceutical Journal
Vol 270 No 7244 p506
12 April 2003

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Congress summary  April 12    April 5

Related websites
American College of Cardiology congress (more)
Journal of the American College of Cardiology (www.cardiosource.com)

Cholesterol absorption inhibitor adds to reductions in heart disease marker

Adding ezetimibe (Ezetrol), a cholesterol absorption inhibitor, to low-dose simvastatin (Zocor) gives an additional reduction in C-reactive protein (CRP), an important independent marker for cardiovascular events and atherosclerosis.

Dr Philip Sager, cardiovascular clinical project director, Schering Plough, told The Journal, that when added to simvastatin at doses of 10mg, 20mg, 40mg or 80mg, ezetimibe 10mg produces further reductions in lipid levels.

In a trial of 668 patients, low-density lipoprotein cholesterol was reduced by 49.9 per cent in the ezetimibe plus simvastatin group compared with an average of 36.1 per cent in those given simvastatin alone (P<0.01). In addition, there were further reductions in CRP (34.8 per cent vs 18.2 per cent, P<0.01). The reductions in CRP seen with ezetimibe plus 10mg simvastatin were the same as those for 80mg simvastatin alone (Journal of American College of Cardiology 2003;41[Suppl A]:316A).

Dr Sager, speaking during the ACC meeting in Chicago last week, said that doctors are often not good at titrating patients to higher doses of statins and there are concerns about adverse effects of taking high doses. Adding a second drug might be seen as an easier way of achieving lower lipid targets. He noted that in the United States combination products have become more popular for treating hypertension in order to improve patient compliance. A combination of ezetimibe and a statin is under development.

In trials, ezetimibe monotherapy had an adverse event profile similar to that of placebo and when combined with statins and adverse events were similar to those seen with statins. Dr Sager said that reversible episodes of elevated liver enzymes had been seen, but such rises had also been seen with non-systemic treatments such as resin binding agents and aggressive low-fat diets.

In order to see if the effects of ezetimibe on CRP lead to atherosclerotic regression, a phase III study in Europe, under the acronym ENHANCE, will look at the effects of ezetimibe 10mg and simvastatin 80mg in comparison with simvastatin 80mg alone on carotid artery wall thickness in patients with high cholesterol levels. Other ongoing trials are looking at combination therapy in patients with hyperlipidaemia and either chronic kidney disease (SHARP trial) or aortic stenosis (SEAS trial).

Ezetimibe is expected to be launched in the United Kingdom later this year by a Merck Schering-Plough joint venture.

The Pharmaceutical Journal attended the American College of Cardiology congress courtesy of Merck/Schering-Plough Pharmaceuticals