Ask Dr. H: Best treatment for bad cholesterol

Question:

In light of the recent ENHANCE study, I am in a quandary as to whether I should switch my cholesterol medication from Vytorin (a combination of Zetia and the statin drug simvastatin) to simvastatin alone. It seems as if Zetia doesn't do any good, and switching to a generic drug will save me a whole lot of money. What's your advice?

Answer: The folks at Schering-Plough, manufacturers of Zetia and the combo drug Vytorin, had hoped that the ENHANCE study would show an "enhanced" effect of adding Zetia (a drug that blocks cholesterol absorption from the digestive tract) to 80mg of the statin drug simvastatin (brand name: Zocor).

The study population was a group of patients with very high inherited cholesterol levels.

In the ENHANCE study, the Vytorin (10mg Zetia/80mg simvastatin) combo drug lowered LDL "bad" cholesterol by 55.6 percent versus 39.1 percent with 80mg simvastatin alone. Vytorin also reduced the C-reactive protein level (a presumed biomarker reflecting underlying blood vessel inflammation caused by plaque) in patients more so than 80mg simvastatin alone (49.2 percent versus 23.5 percent). But hopes were dashed when ENHANCE showed that there was a small but not-statistically significant increase in the buildup of carotid artery plaque in the Vytorin group versus the 80mg simvastatin group.

While ENHANCE was not intended as an outcomes study looking at reduction of heart attacks, stroke and death, it has left many doctors questioning whether Zetia does any good despite its additional benefit in lowering LDL "bad" cholesterol.

Adding Zetia to a statin lowers LDL by an additional 18-23 percent; doubling the dose of a statin such as simvastatin (Zocor or Lipitor) lowers LDL by 6-9 percent. But if it does not translate to less illness and death, where's the benefit? That is, after all, why doctors prescribe these drugs in the first place. Vytorin's own prescribing information states: "No incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established."

To confidently answer the question of whether Zetia improves clinical outcome and doesn't just give you better lab results, the IMPROVE-IT trial is under way. It will include up to 18,000 patients and will conclude in 2012.

In view of the ENHANCE findings, my advice is to try statins (e.g., simvastatin and Lipitor), fibrates (e.g., Tricor or Antara), and niacin alone or in combination before considering Zetia.