Put Vytorin back—way back—on the shelf

Last month, Merck/Schering Plough Pharmaceuticals finally released the disappointing results of a clinical trial, completed nearly two years ago, on the hoped-for ability of Vytorin to halt the progression of thickening in the carotid arteries (the two major blood vessels in the neck). In the interim, with the public totally unaware of those results, Vytorin continued to be heavily advertised to the public and widely prescribed by physicians.

That two-year study of 720 volunteers with inherited very high cholesterol levels, showed no significant differences between the carotid artery scans of those patient who took Vytorin (a combination of Zocor and Zetia) and those who took Zocor alone, despite the finding that the Vytorin takers had lower LDL cholesterol levels.

I think this study has two important implications, over and above the money wasted on purchases of Vytorin:

1. There’s no connection between the lowered LDL cholesterol levels and the lack of change in carotid artery thickening (actually the Vytorin group had more plaque formation which was not, however, statistically significant). This is unlikely in view of the overwhelming evidence that ties LDL cholesterol to cardiovascular disease. Perhaps the study was not long enough.

2. There is fallibility in clinical studies that use so-called intermediate end-points (imaging techniques, biochemical changes) instead of real events (heart attack, stroke, death). There are still many unknowns about the causes of heart attacks; fully half of coronary-disease deaths occur in people with no discernable risk factors.

And what about the patients and professionals who believed the TV ads and the hype of the drug reps and spent large sums of money on a drug that was very likely not helping them?
Here’s my advice:

Regard Zetia for what is—excessive and expensive baggage and a relatively weak LDL cholesterol lowerer. It should only be used by those who cannot tolerate statins or by the few patients who are already on high-dose statin therapy and are not achieving desirable LDL cholesterol levels. As for the combination product Vytorin? Put it back—way back—on the shelf and stick to a statin drug, preferably one available as a less-costly generic version. Read our CR Best Buy Drug report on statins to see which ones we recommend.
—Marvin M. Lipman, M.D.

Dr. Lipman has been Consumers Union's chief medical advisor since 1967. He is a diplomate of the American Board of Internal Medicine (certified in endocrinology and metabolism) and is clinical professor of medicine emeritus at New York medical College.

Comments

[Gregor Beck]

Regarding prices for Lipitor in Saskatchewan:
I have been taking Atorvastatin/Lipitor for several years now.
The price I am paying is CAD $ 91.36 as of Dec 21, 2007 for 34 Tablets Lipitor 20 mg, Atorvastatin Calcium 20 mg.
Best Regards Gregor Beck

[Concerned Reader]

Dr. Lipman's comments are accurate albeit a little inflammatory. The ENHANCE trial to which he is referring to in his essay is not really a study that will change clinical practice for many doctors. Unfortunately, the study just is not very good.

There are 2 reasons why the study is not very applicable to the majority of patients. First, the patients in the study had FH, a genetically inherited lipid disorder. Patients with this disorder have much higher levels of certain lipids than the average patient. Secondly, the end point in the study was a change in carotid intima-medial thickness (CIMT). This means that the authors of the study looked to see if there was a change in carotid wall thickness related to taking the drug rather than looking to see if the drug actually helped people live longer or have fewer heart attacks and strokes. CIMT measurements are very difficult to make because differences are measured in millimeters. The ability to detect minute differences is not very good. Surrogate markers are just not good substitutes for true, hard end points.

I agree that Vytorin, which is a combination of simvastatin and ezetemide, is not the ideal drug, but my reasons differ. Drug companies make combination pills of their medications when their drugs are about to become available in generic form because the new combination pill can be patented and sold exclusively in non-generic form. This of course means that the new pill is more expensive and more profitable. The consumers get the convenience of taking fewer pills but pay a hefty price for that privilege. The ezetemide in Vytorin does not make the pill bad but the marketing does.

Do not discount the beneficial LDL or bad cholesterol lowering effects of ezetemide because of the ENHANCE trial. There is a role for the drug as Dr. Lipman’s essay points out. This small, insignificant study is one of hundreds of studies that are published every day that will not change clinical practice for many physicians. Some research studies are just not very good.

[Erwin Hunsberg]

From varios doctors and health
reports VYTORIN received splip opinons either not too
helpful, causing health problems compared with other
cholesterol lowering medicine beside too costly. What and whom to believe ? Since weeks I am taking VYTORIN 10/20 so my doctor recommends.EH5/19/08