Zetia: Down for the count?

For the second time in six months, ezetimibe (Zetia), a featherweight LDL (bad) cholesterol fighter, has taken a hit, and this blow could well end its career. The referee, with the initials FDA emblazoned on his white lab coat, has begun the countdown.

Ezetimibe (made by Schering-Plough and still on patent as the brand name Zetia) was approved in 2002 for use with a statin to achieve additional small reductions in LDL cholesterol, compared to just the statin alone. In 2004, when Merck's brand of simvastatin, known as Zocor, was about to go off patent, Merck teamed up with Schering-Plough to produce a new patented product called Vytorin, a combination of simvastatin and Zetia. A vigorous advertising campaign resulted in billions of dollars in sales.

Then, in February of this year, the first blow landed: A two-year study showed that the combination product was no better than simvastatin alone in decreasing the growth rate of plaque in the carotid arteries. At that time the Consumer Reports Health blog referred to ezetimibe, alone or in combination, as "excess and expensive baggage, to be put back on the shelf and be used only in people who were either intolerant of statins or in conjunction with a generic statin only when LDL cholesterol goals were difficult to achieve."

The second, and much more devastating, punch was landed in early September when The New England Journal of Medicine reported the preliminary results of a study that pitted Vytorin against a placebo to compare the number of strokes and heart attacks that occurred in older people with narrowing of the heart’s aortic valve. After five years, except for a decreased number of coronary artery bypasses in the Vytorin group, there were no differences in the incidence of strokes and heart attacks.

What did show up, however, was an increased number (101 vs. 65) of cancer cases and deaths (37 vs. 20) from cancer. Also analyzed in that issue of the Journal were two other similar ongoing studies in England. According to those studies, looked at after just two years, that increased cancer incidence could not be confirmed. [The FDA also reported that their analysis of the available interim data from the two ongoing English studies of Vytorin, showed no increased incidence of cancer.] But a statistically non-significant trend toward increased cancer deaths (97 vs. 72) was noted.

The final results of the English studies will not be known until 2012. The U.S. Food and Drug Administration is studying the situation and is expected to make an announcement in six months.

As with the Avandia caper, health professionals and their patients are faced with a conundrum. The issues now are not ezetimibe's relatively limited ability to reduce LDL cholesterol or its cost, but its safety. Good scientists are on either side of the question: Is the evidence sufficient to indict? Consumer Reports believes that whenever safety is an issue with a drug, caution has to be brought to bear until more definitive studies are done. Our previous cautions about Zetia, and its use in the combination product Vytorin, can now be extended to exclude its use in new patients, especially those with a personal history of cancer. The reasons for maintaining patients on Zetia or Vytorin should be carefully examined and its use limited to those with multiple coronary risk factors who cannot tolerate statins.

Ezetimibe is down, a recipient of the one-two punch, and the referee has begun his slow count: one, two, three …

CR’s Recommendation: Vytorin or Zetia should not be prescribed for new patients, particularly those with a personal history of cancer. Patients currently taking Vytorin or Zetia should be reevaluated to make sure the potential benefits outweigh the potential risks. Under no circumstances should a patient discontinue any medication on his or her own volition without discussing the matter with a physician.

—Marvin M. Lipman, M.D., chief medical adviser

Find out if statins, fibrates, and the Mediterranean diet (subscribers only) could help lower your cholesterol, and take a look at our free Best Buy Drugs report on low-cost cholesterol-lowering drugs.

Comments

[Ron]

I have been taking Zetia for two years or more along with 200mg Niaspan and 80 mg Lipitor. Zetia solved the last problem of LDL levels.
Early this year my med insurance company refused Zetia. since that time my LDL has risen to 211 and I have just come out of hospital after a stroke and loss of sight in my left eye. The hospital physician gave me a scrip for Zetia and this time it was filled with no problem. all the time I have been taking Zetia, I have not had any significant side effects or problems.
After this recent episode I have to ask, What the hell is going on here?

[Debbie]

I have been on Zetia for just over one month. Since starting it I have had urinary problems. I can not make it to the bathroom fast enough, and also seem to produce more urine than normal. I was taking a diretic for fluid retention and had to stop it as combined with the Zetic I would be in the bathroom all day, and end up dehydrated! Has anyone else had this response to taking Zetia? If yes, did you find a way to correct it or did you stop taking it? I am not taking a statin with it.

I have also been more tired and in more pain than normal. Sounds like from reading the other comments, this is a problem for many people.

My mother in law recently had 2 stents put in after having a heart attack. They found she had high cholestrol when checking her blood levels after her surgeries, and also put her on Zetia. Each time she takes it, her heart starts racing and when she check her heart rate it is very high. She has just stopped taking it due to this. Any comments would be appreciated!

[Marie Fleming]

Why did the study of Vytorin assume that the increased cancer was due to the Ezetimibe and not the Statin ingredient? Also, the increase in numbers of cancer deaths you give is absolute- you did not state if this increase was statistically significant for the size of population in the study. You do note that the British studies showed no statistically significant increase in cancer.

It would seem to me that your analysis and reporting of these studies is unnecessarily skewed towards damning Zetia and favoring Statins.

[Doug Hilton]

Have been taking zetia and lipitor started losing muscle in my right arm and having muscle twitches, also pain in joints, anyone with these problems.

[Maureen]

I'm worried to death about what to do. I have been taking Zetia for a few years and during that time I never felt good, always aching or tired. In 1-09 I had to have 2 stents put in my heart due to being blocked,also my liver enzine test came back with a count of over 900. They took me off the Zetia and I had been off of it up until 2 days ago due to my cholesterol being over 300. Since I've taken it my legs ache so bad I can barely walk. What is one to do when all we're told is to take a pill for everything and then we find out that these are killing us. Any suggestions from anyone who has lowered their cholesterol naturaly???

[Eleanore]

I have been using Zetia continuously for about 1 year. during this time, I have noticed increasing muscle pain, occasional lightheaded, nausea. After researching Zetia from different websites, I decided to discontinue taking my prescription. I also stopped taking Tricor. The side effects from both drugs are practically the same. My cholesterol dropped some, but I cannot continue taking meds that will increase the pain and incapacitate me. It has been almost a week and I am beginning to feel much less pain. The latest comments of cancer connection is enough to say goodbye to Zetia.

[NameTricia koltko]

i was given zetia to help the lipitor reduce my colesterol. after the second time i took it i started having anxiety attacks. on the fifth day i had a mild heart attack and stoped taking the zetia. within a week i had a mini stroke (tia). the took me off the lipitor because of liver damage and i now take three fish oil pills a day.

[Debbie]

My husband and I have been taking zetia for over a year and so far we have had no side effects from it. We werent ablet to take two other drugs zocor was one of them. It seems most of the meds we take will either cure you or kill you what do we do?

[Sandie]

Has anyone heard that cholestrol medication may cause head hair to break, or to lose hair? I started taking Zetia and Pravastatin 6 months ago, and in the last month I have noticed that the hair on the crown of my head and front hairline looks like I am growing new hair, but my hairdresser informed me today, that is not new hair, it is broken hair, and she had noticed that with several other of her customers, and they had all been taking cholesterol medication. I am taking other medications, for other issues, but the cholesterol medication is the only new one within the last 6 months. Any comments would be appreciated.

[Lois Getz]

I have sandy bowel movements for over a year,,,perhaps it's the Zetia?????? No illness, no pain.

[tom moebius]

I have been on Zetia for 8 months, 10mg., & Crestor @ 20mg. for the past 21 months since quad by-pass, I'm 62. 190 was my choelesterol, now 135, HDL 71. My liver produces choelesterol at a higher then normal rate; my consumption of choelesterol is never more then 30mg. a day; most days 2 or 3mg. & NO red meat other then 4-5oz. chicken breast maybe 2 times aweek. Saturated Fat no more then 5mg. a day, if that much. My Great, Grand and Father all died of heart disease. My left carotid artery went from 10% to 60% blockage in one year; that was 8 months ago. November 15, 2008, still at 60%. Diet-Zetia-Crestor is working for me. I find it difficult to believe Cancer is due to Zetia, vs. the individuals previous life style and poor eating habits, but who is to say.

[Janie Sheehan]

I had a hemorrhagic stroke 5 years ago which left me paralyzed on my right side. I thought I was getting quite a bit of motion back, walking fairly well, and then it reversed and worsened. By a few months ago I could not even get out of a chair without help, and then had to hold on for the first dozen steps before I was steady enough to walk with a cane by myself. A friend mentioned how she'd taken lipitor and zetia (exactly what I had been taking for 5 years) and had to use the sink to pull herself up from the toilet. I told my new doctor (I'd retired to Florida) and she told me to quit taking the lipitor but continue taking the zetia. That was two months ago and while my muscles are still weak, I can get up and walk by myself. I'm wondering if I should also quit the zetia. My total cholesterol after 2 months off the lipitor has gone up to 203.

[Pamela King]

I was taking Zedia and Vitorin from 8/07 - 1/08 In May 08 I was diagnosed with stage 4 colon cancer. Any corelation?

[Everett Richardson]

My sister was just diagnoised with cholangiocarcinoma. She has been on Vytorin for three years. Does the Vytorin studies indicate any higher proponderance of a specific type of cancer?

[Marilyn Mann]

If someone is able to tolerate Vytorin (simvastatin/ezetimibe), they are by definition able to tolerate simvastatin, which is a statin. Therefore, they could easily switch from Vytorin to simvastatin (or possibly another statin).

Bear in mind that some people are intolerant to a particular statin, but can tolerate another statin.

If someone is on ezetimibe alone (Zetia) because they cannot tolerate statins, they may want to consider other alternatives, such as resins or niacin.

[M. D. Weston, O. D.]

My wife has been taking Vytorin for three years. She has just been diagnoised with large cell b lymphoma. Dr. Rosenfeld on Fox News Sunday advised all doctors to stop Rxing this drug until the study is finished.