Should I Take Zetia or Vytorin?

Effectiveness of the cholesterol medications Zetia (ezetimibe) and Vytorin (simvastatin/ezitimibe) were called into question this week in well-publicized reports from the American College of Cardiology meetings, as published in the New England Journal of Medicine.

Specifically, the ENHANCE trial found that although adding ezetimibe to maximal statin doses over 24 months effectively lowered bad cholesterol (LDL) and inflammatory markers of heart disease risk, it did nothing to decrease the size of cholesterol plaques in the large neck arteries (carotid arteries). Such plaque size is a well-documented marker for heart attack risk.

Importantly, the ENHANCE trial does not raise safety concerns about ezetimibe, but rather questions its effectiveness in achieving one clinical outcome. Additionally, the study was conducted on a select population of patients with familial hypercholesterolemia and a very high mean LDL level of 317. The patients did not achieve the target cholesterol goals known to you loyal Bloggers. These facts make the study outcome difficult to interpret and somewhat controversial.

So, what should you do if you are taking these medicines or if you have non-goal cholesterol levels?
* Achive LDL levels at ATP III-recommended levels.
* Utilize lifestyle changes like diet and exercise in addition to optimal sugar and blood pressure control.
* Realize that statins are the first drugs of choice, and should be titrated to the highest tolerated dose to achieve the target.
* Know that if optimal statin dosing does not achieve the goal, additional therapy is needed. Options include niacin, bile acid resins (like Colestipol), psyllium (like Metamusil), and fibrates (like Tricor), in addition to cholesterol absorption inhibitors like ezitimibe (Zetia). Some authorities believe that the non-ezetimibe options should be tried first given results of prior studies.

Ongoing trials will help clarify these issues further. Stay tuned to the Blog, and, as always, if your levels are not at the goal, ask your doctor "why not?"

Zetia, Premarin, and the safety of medicines

Part of our Federal tax money goes to support the Food and Drug Administration (FDA), charged with overseeing the safety of medicines sold in America. The pharmaceutical companies are quick to describe how very expensive it is to take a proposed new medicine through the FDA approval process. So, why is the effectiveness and even safety of Zetia, (ezetimibe; a component of Vytorin) a cholesterol reducing medicine, being questioned now quite some time after its FDA approval.

Everyone would like their risks of heart attacks and strokes to be reduced. This is the ultimate goal of preventing and treating cardiovascular diseases, the number 1 cause of deaths in the US. Heart attacks and strokes are thought to be caused by cholesterol plaque being deposited in the walls of blood vessels thus narrowing them or by clots lodging in the blood vessels of the heart and brain.

The ideal means of experimenting with a proposed medicine for reducing the risks of heart attacks and strokes would be to treat some people with the medicine and not treat others. Then, wait to see which group gets more and which group gets fewer heart attacks and strokes. And, ideally, everyone in both groups would have the same diet, stresses, living conditions, etc. Well, reality is far from the ideal and people tend to live for a long time so either the groups on the medicine and on a placebo need to be huge or the groups need to be followed for decades in order to get statistically valid results to answer the question - does the medicine prevent heart attacks and strokes.

We have thought that blood cholesterol levels served as indicators of what was going on in the blood vessel walls but this has not been shown to be the case for people on Zetia or for women taking Premarin (an estrogen hormone supplement). When the expensive studies were done, there was not a close correlation between the cholesterol levels and the diameter of the blood vessels (for Zetia) or the numbers of heart attacks and strokes (Premarin). We are just more complicated than was thought and these two surprises to medicine may end up having a great influence on how medical research is done and medicines approved in the future.