Vytorin and Zetia Lower Cholesterol But Do Not Improve Health

Keris KrennHrubec and Diana Zuckerman, PhD

There are many cholesterol-lowering medications on the market today, but which of these drugs improve health and save lives? Just because a drug lowers cholesterol doesn’t necessarily mean that it will do either. What do the latest research studies tell us about Vytorin and Zetia, two of the most popular (and expensive) cholesterol medications?

A new study published in the New England Journal of Medicine in November 2009 reported that patients taking Vytorin were more likely to have heart attacks or die from heart disease than patients taking a combination of Zocor (an older statin) and Niaspan, an extended release form of niacin (a type of vitamin B).1 Zocor and Niaspan are both available as less expensive generic medications. The study included only 208 patients, because it was stopped early for ethical reasons when it became clear that patients taking Vytorin were benefiting less than the other patients.  Note: In 2011, the FDA recommended that patients should avoid taking an 80 mg dose of Zocor (also known as simvastatin) because of muscle injury risk.

Zetia has been widely advertised as better at treating cholesterol and heart disease than its competitors. About 70 percent of people who take Zetia take it as Vytorin, which is a combination of Zetia and Zocor (also known as simvastatin).

The new study was a comparison of Zocor with niacin compared to the combination of Zocor and Zetia, the ingredients in Vytorin.

A previous study had indicated that the addition of Zetia to Zocor is also not effective compared to Zocor alone. After Zetia was approved by the Food and Drug Administration, the drug companies that make it, Merck and Schering-Plough, conducted a two-year clinical trial of 720 patients. Half the patients were given Vytorin (the combination of Zetia and Zocor) and half were given Zocor alone.2 The results of this study were supposed to have been released in March 2007, however they were not published in a peer-reviewed journal until March 2008. When they finally were made public, the results indicated that patients taking the Zetia-Zocor combination drug (Vytorin) were at the same risk for heart disease as the patients who took Zocor alone.

Zetia had been previously shown to reduce cholesterol by about 15-20 percent, which makes it a better cholesterol-lowering medication than traditional drugs like Zocor. However, Zetia had not been shown to prevent the buildup of fatty plaques on the insides or arteries that commonly lead to heart attacks and strokes. The goal of the Vytorin vs. Zocor study was to prove that the combination of Zetia with Zocor is better at reducing this buildup than Zocor alone, which would indicate that it is probably more effective at preventing strokes and heart attacks.2

However, the results show that while Zetia combined with Zocor is more effective at lowering cholesterol, it is not better at reducing plaque build up in the arteries than Zocor alone. On the contrary, the arterial wall was somewhat thicker for patients taking both drugs.2 In fact, 2 patients taking the combination pill died, compared to one taking Zocor, and 3 of the patients taking the combination pill had non-fatal heart attacks, compared to 2 taking Zocor. None of these differences were statistically significant2, but they all suggest that Zocor alone is a better choice than Zocor combined with Zetia. The bottom line is: why take a combination of two drugs that has no clear health benefits compared to taking just one of the drugs?

The study of Zocor plus Niacin vs. Vytorin also found more plaque build up for the latter, compared to Zocor plus Niacin.

Doctors and patients had assumed that Zetia is worth the cost because it is so effective at lowering cholesterol. But, after the March 2008 study was published, doctors were advised that Zetia should only be used if all other medications have failed. Although prescriptions for Vytorin and Zetia decreased, the drugs continued to sell well. The November 2009 study findings may change that situation, and also should be a wake-up call for the FDA to re-evaluate their approval of Zetia.

It is important to keep in mind that lowering cholesterol is a means to an end (better health), not a sign of health in and of itself. And, of course, all drugs have unwanted side effects and potentially serious risks. The listed side effects for Zetia include: stomach pain, tiredness, allergic reactions, and joint pain. Rarely, patients also experience severe muscle problems with symptoms of muscle pain, tenderness, or weakness caused by muscle breakdown.3

If a drug that lowers cholesterol does not improve health, and other drugs are more likely to improve health, then the risks outweigh the benefits.

References

1. Taylor, AJ et al. (2009) Extended-release niacin or Ezetimibe and carotid intima-media thickness. The New England Journal of Medicine. Published at www.nejm.org November 15, 2009.

2. Kastelein, J et al. (2008). Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. The New England Journal of Medicine. 358, 14: 1431-1443

3. FDA Patient Information Sheet: Ezetimibe (marketed as Zetia). (July 2006). Retrieved from: http://www.fda.gov/Cder/drug/InfoSheets/patient/ezetimibePIS.htm