VYTORIN, ANOTHER DISAPPOINTMENT

The prelim, interim analysis of SEAS study was released on monday. The SEAS study is a study to study the effect of intensive LDL-cholesterol lowering, on patients with aortic stenosis. Aortic stenosis is a common condition in elderly caucasians when the aortic valve ( the main outlet valve of the heart ), gets narrowed ( usually from atherosclerosis ) and so restricts blood flow out of the heart. The treatment is usually aortic valve replacement surgery. The primary endpoint of SEAS was a composite of cardiac events and aortic valve replacement surgery. The study failed to meet the primary endpoint. It also failed to meet the secondary endpoint of composite CVS events. But that was not where the excitement was. It was also revealed, ( transparency, after the ENHANCE fiasco ) that there were 102 cancers in the treatment arm and 67 in the placebo arm. When the researchers contacted their colleagues doing other clinical trials with Vytorin ( there are two more large scale study in the pipeline, the IMPROVE-IT and the SHARP study ), they quickly check their numbers, and found that it both the studies ( which is still in progress ), there were 4 times more cancers in the treatment arm then in the placebo arm. The cancers noted were of different types. Is this a chance finding or is real. Are the cancers caused by Vytorin or ezetimide, bearing in mind that Vytorin is ezetimide + simvastatin. Simvastatin, did not show a cancer-producing tendency in all their previous large trials. Or could it be that intensive LDL-cholesterol lowering is the cause. I have always held the rather unpopular ( non clinical guideline ) view that you must never lower LDL-Cholesterol too much. In the SEAS study, the average LDL-cholesterol level, in the vytorin arm was 52 mg%. I am of the opinion that the body cells need some cholesterol for their proper function. Knocking off most of our LDL-cholesterol may be good for prevention of atherosclerosis, but may be very bad for our proper cell function. However, most of the " big guns " in cardiology, is against my view. The standard answer is that there is no association, between cholesterol lowering and cancers. I can surely remember some of the earlier trials with " clofibrates " which showed such a " trend " too. Well, now that this " trend " is again seen in the SEAS, SHARP and IMPROVE-IT, maybe all my "gurus " will sit up and take notice. I have this feeling that God gave us LDL-cholesterol for a good reason, not just to harm our arteries, but perhaps also to protect us for malignant cell multiplication. I suppose, until more studies are done, we may not be sure. But one thing is for certain. The days of Vytorin are numbered. Of course shares of MSD in Wall Street fell, on the monday release of the interim analysis. If I had a choice, I will not put my patients on Vytorin and I will not lower my patients LDL-cholesterol below 80mg%, unless of course I wish them to run the risk of cancers. But as a good doctor, I will not do that.