Trial Results for the Cholesterol Blocker Zetia Have Not Been Revealed

Friday, February 15, 2008 by: Teri Lee Gruss
Tags: Zetia, health news, Natural News

(NewsTarget) Has your doctor prescribed Zetia or the combination drug Vytorin to you to lower your total cholesterol or your LDL cholesterol? If so, you and your doctor should know that data from clinical trials designed to assess the effectiveness and safety of Zetia has yet to be published even though the FDA approved Zetia five years ago.

A recent report titled Data About Zetia Risks Was Not Fully Revealed by Alex Berenson appeared in the New York Times (NYT) during the busy week before Christmas, December 21, 2007.

Blocking Cholesterol

Zetia (ezetimibe), manufactured by Schering Plough, was approved by the FDA in 2002. According to the NYT article, it was approved after a 12 week clinical trial that involved 3,900 people. Vytorin, a combination drug containing Zetia and Zocor was approved by the FDA in July of 2004. Zocor is Merck's statin, simvastatin.

We have all seen the clever direct-to-consumer ads for Vytorin. The ads emphasize a genetic link to elevated cholesterol. In fact, familial hypercholesterolemia (HeFH) is a very rare disorder.

According to Merck, "Patients with this uncommon genetic condition usually have very high cholesterol levels. HeFH occurs in approximately 0.2 percent of the population".

Public Citizen's website Worstpills.org explains that Zetia works by "partially blocking the absorption of cholesterol in the intestine. It doesn't decrease the production of cholesterol by the liver and may actually increase the production of cholesterol".

Worstpills.org notes that Zetia was approved even though a FDA Pharmacology reviewer warned of serious safety issues with Zetia, both alone and combined with statins.

Worstpills.org says that "evidence for the treatment of elevated cholesterol is weak for people who do not have CVD [Cardiovascular Disease] particularly for those without hypertension, who do not smoke, are not obese, don't have a close family history of CVD or for those who have not already experienced a heart attack or stroke".

The ENHANCE Trial - Where's All the Data?

Mr. Berenson's NYT article notes that the ENHANCE clinical trial, designed to assess the efficacy (effectiveness) of Zetia ended in April of 2006, yet data of possible serious adverse effects remains unpublished.

According to a Merck press release, "The primary objective of the ENHANCE trial is to measure the change in the intima media thickness at three points of the carotid artery (the internal carotid, carotid bulb and the common carotid) at the beginning of the study and at two years".

Since its approval, Zetia has been prescribed to millions of Americans, a brisk seller with sales of about $5 billion in 2007 according to the NYT article.

Public Citizen's website worstpills.org has recommended that the public wait until October of 2009 before using Zetia. This is their "7 year rule", a recommendation designed to protect the public from unknown or unreported adverse side effects of drugs due to the short duration of many industry clinical trials and the FDA's approval of drugs.

To date, we have no significant scientific evidence that Zetia prevents heart attack or stroke, only that it blocks the absorption of cholesterol in the intestines during clinical trials of short duration. Public Citizens' "7 year rule" seems prudent.

Safer Than Statins?

There are increasing questions regarding the possibility that Zetia may increase the risks for rhabdomyolysis (muscle cell damage) hepatitis, pancreatitis and depression.

According to the NYT article, both Canada and Australia have issued warnings for these potential risks.

While the manufacturer of Zetia claims that it has improved safety over other cholesterol lowering drugs, particularly statins, worstpills.org notes that there is "no actual proof that it is safer".

An FDA reviewer notes that in animal studies, Zetia alone showed toxicity to heart, lymph nodes, kidneys, bone marrow, lung and liver tissue. Combined with statins, increased toxicity was found in liver, stomach, skeletal muscle, spleen, heart, testes, lung and prostate tissue.

In 2004 and 2005 the FDA "added new warnings to the list of adverse events associated with the use of Zetia in the drug's professional product labeling" according to worstpills.org (WPO). WPO lists the following adverse effects included in the updated FDA warnings:

* Angioedema: described as "a serious allergic skin condition characterized by patches of circumscribed swelling involving the skin and its subcutaneous layers, the mucous membranes, and sometimes the heart, liver, or intestine"

* Inflammation of the gallbladder and gallstones

* Inflammation of the pancreas (pancreatitis)

* Nausea

* Diffuse muscle pain and weakness (myalgia) including muscle disintegration (myopathy/rhabdomyolysis),

* Elevated creatine phosphokinase (a possible indication of kidney dysfunction)

* Elevated liver enzymes

* Inflammation of the liver (hepatitis)

* Low platelet count (thrombocytopenia)

According to the Merck press release: "The ENHANCE trial is complex and is being conducted with great care," said John Kastelein, M.D., Ph.D., professor of medicine and chairman of the Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.

"We anticipate that results of the ENHANCE study will be presented at the American College of Cardiology meeting in 2008, dependent upon successful completion of the data analysis."

Why should anyone take Zetia or Vytorin before this vital information is made available to the medical community and to the public, especially when we have no evidence that these drugs prevent heart attacks and strokes?

The omission of original clinical trial data in the FDA drug approval process is one more sign and symptom of a chronically diseased process.

Sources:

Data About Zetia Risks Was Not Fully Revealed by Alex Berenson, New York Times, 12/21/2007
(http://www.nytimes.com/2007/12/21/business/2...)

Merck Press Release
Merck/Schering-Plough Pharmaceuticals Provides Update on ENHANCE Trial
WHITEHOUSE STATION, KENILWORTH, N.J., Nov. 19, 2007 - Merck/Schering-Plough Pharmaceuticals today announced that an independent panel of clinical and biostatistics experts was convened on Friday, November 16, 2007 to offer advice about the prospective analysis of the ENHANCE trial
(http://www.merck.com/newsroom/press_releases...)

Public Citizen: Worstpills. Org
(http://www.worstpills.org/)

(http://www.fda.gov/cder/foi/nda/2002/21445_Z...)
(Have not been able to open links)

About the author

Teri Lee Gruss, MS Human Nutrition