LOWERING CHOLESTEROL WITHOUT REGRESSING PLAQUE - A PROBLEM WITH EZETIMIDE

EuroPCR is still ongoing in Paris. I was looking very hard to see if there are any landmark information coming out of Paris at this time. Looks like the answer is now. Angioplasty and stents have reached a plateau and we are seeing refinements, and a shift to other forms of intervention like Renal Denervation and TAVI. Maybe I should mention two small piece of information out of Paris. Firstly, looking on at Resolute all comers, the diabetic subset did rather well. In fact a statement was made at the presentation that Endeavor resolute may be the stent of choice in Diabetic coronary artery disease. The TLR was in the range of 3-4%. That is very good. The second piece of information, is the launch of the 10,000patient strong Global Leaders, to test the Biomatrix Biolimus A9, abluminal biodegradable polymer coated stent, against another -limus ( unnamed ), which I guess must be Xience V. Lets see what happens in 3-5 years. I fear that after 5 years, the comparision is meaningless ( besides one up manship ), as the clinical issues and target may have moved. Anyway, Biosensors have decided to embark on it, so it is up to them

Anyway, today, I picked up a review of a paper by the group from University of Virginia Health System led by Dr Amy West. They studied a group of about 67 patients with peripheral vascular disease, involving the superficial femoral artery. 16 of the group ( those already on simvastatin and their LDL-C was controlled ) were on simvastatin, another 16 were on Vytorin ( simvastatin + ezetimide, and their LDL-C was also in the controlled range ) and the third group whose LDL-C was not controlled by simvastatin alone, had ezetimide added to bring the LDL-C down. All three groups achieved the target LDL-C of 80mg/L. All these patients had baseline, 1yr, 2 yr MRI scan of their superficial femoral artery, plaque volume. After 2 years of followup, group 1 ( simvastatin group ), had plaque regression, group 2 ( Vytorin group ), had no change in plaque volume, but in group 3 the plaque volume increased ( by almost 4% % in two years). Now this is worrying, as this same findings were also noted in the earlier ENHANCE, and ARBITER 6 study.
This raises two big issues. 1. Does ezetimide reduces LDL-C but progresses plaque? and what are the consequences of this, is it hard plaques or soft plaques? 2. How do we understand lower LDL-C with increase plaque volume as a concept? So cholesterol is not the only component of plaque build-up, and more importantly maybe smooth muscle cell proliferation or other cellular reactions. We can lower LDL-C and yet promote plaques. This has consequences.
So ezetimide is not so straight forward. Looking at LDL-C alone to see benefit in CAD treatment, may not be sufficient. It is true that this study is a small study and that MRI of superficial femoral artery is not a standard way of estimating plaque volume. Be that as it may, these findings are in line with two other bigger study, making it three studies over a period of time, over three different cohorts. Now that must mean something.
I suppose we should watch this scene carefully.
For the moment, I would only use ezetimide in statin intolerant patients, who have established CAD, and who cannot achieve their LDL-C target of 100 mg/L. Yes, I am rather conservative. By the way, ezetimide is not cheap either.