Zetia: Why does Merck do this... again?

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Today I had my first group appointment led by my new endocrinologist (a.k.a. my favorite endocrinologist) at the Palo Alto Medical Foundation, Dr. Randolph Linde.

After seeing my lipids, Dr. Linde too me off of Zetia and left me only on Simvastatin (Zetia and Simvastatin combined make up Vytorin, which I had been on for almost two years now).

I happened to learn during my appointment that late last year, Merck, the manufacturer of Zetia made headlines ONCE MORE with this drug. The NYT posted this late last December:
Data About Zetia Risks Was Not Fully Revealed
New evidence shows that the drug makers Merck and Schering-Plough have conducted several studies of their popular cholesterol medicine Zetia that raise questions about its risks to the liver, but the companies have never published those results.

Partial results of the studies, alluded to in documents on the Food and Drug Administration’s Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

Furthermore, in January the Washington Post published:
Drug Doesn’t Slow Artery Clogs, Study Says
A popular cholesterol-lowering drug failed to help slow the buildup of artery-clogging plaque in a long-awaited study, the companies that market the medication said yesterday, raising questions about whether its use should be limited.

The drug, Vytorin (a combination of Zetia and Zocor), also did not reduce the thickness of plaque lining artery walls, a significant disappointment for the manufacturers.

“Obviously, we would have preferred a more favorable result,” said Skip Irvine, a spokesman for Merck-Schering-Plough Pharmaceuticals, a joint venture between the two companies that markets both Zetia and Vytorin.

Questions that cross my mind:
-How is it possible that the FDA approves medicines on the basis of lowering cholesterol alone, while not helping (actually going against) reduction in the probabilities of cardiovascular disease?
-What type of principles guide the conduct of Merck and Schering-Plough, when they are unwilling to publish these results (1), the best they can say is they “would have preferred a more favorable result” and they are simply dissapointed? What kind of morals (if any) do these people have?

I am outraged and happy at the same time. Outraged at things like the ones I learned about today and happy that I learned about them and people with ethics like Dr. Linde will let me know about them and hopefully reduce the chances of me having complications down the road.

These things are out right WRONG and should NOT be happening and if they happen, they should be questioned and those who approve and those who put drugs like these go on the market should be held responsible!

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I agree. Cholesterol lowering drugs are very profitable and are being aggressively marketed. My 92 year old father was on Symvastatin for slightly elevated lipids. He started to become confused and seemed to be developing dementia. A little research on the internet showed several studies which had proved that statins cause memory loss and are not necessary or effective in elderly patients. Why don’t doctors read the studies before prescribing potentially dangerous and/or ineffective drugs? Since stopping the Symvastatin, my dad is slowly regaining his cognitive functioning. We were lucky because he was only taking the drug for a short time and it looks like the effects won’t be permanent.

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I have been on and off Lipitor for the last few years even though my LDL was just above 100, they want it below 70 for us diabetics.

I thought about the every three month test to check out my liver and I thought something is not right here, so I stopped taking it on my own. Both my endo and PCP tried to get me back on it, but I refused stating my concerns about liver testing and now I know I was right.

Very scary.

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Manny,

The problem is the use of “surrogate markers” in the drug approval process rather than outcomes. This means they will approve a drug if it lowers some lab test result, without looking at what it does to overall health.

This, by the way, is the problem with all cholesterol drugs, since the data have never shown that lowering LDL improves heath for any but a tiny subset of middle aged men who had already had heart attacks. The surrogate “LDL levels” doesn’t predict cardiac mortality.

This is the problem with drugs that lower blood sugar too. Januvia gave me normal blood sugars, but it did so by turning off the protease the body uses to fight melanocytes that have become melanoma. The FDA has no data about the long term effects on the body of crippling the immune system, which is what Januvia does.

And the scary part is that the only time the mortality data comes to light is when drug companies attempt to show their drug prolongs life. After the failure of the Vytorin trial and the DREAM study which found Avandia was killing people, drug companies will simply NOT run such studies.

The FDA doesn’t require them and the system for tracking side effects after a drug is released is almost completely useless since it relies on doctors a) recognizing the side effect, which studies have shown most don’t–even for well known drugs with well publicized side effects, and b) filing out a very daunting, time-consuming form.

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“How is it possible that the FDA approves medicines on the basis of lowering cholesterol alone, while not helping (actually going against) reduction in the probabilities of cardiovascular disease?”

The reason is that in order to show effect on CVD, you need to run huge trials that last for years. Not only are these hugely expensive, but some people might not to wait 10 or 20 years before getting access to a drug that appears to be effective.

If researchers think that other studies have shown that reducing cholesterol with another medication reduces CVD, then they infer that reducing cholesterol alone is sufficient.

I’m not arguing that this is correct. Many people now think the statins work by reducing inflammation and that the cholesterol lowering is just a “side effect.”

Gary Taubes in his book “Good Calories, Bad Calories” has pages and pages showing how people skipped steps in analyzing all this.

We have no long-term data showing that many of the diabetes drugs, including the newer insulins, are safe in the long term. The FDA could restrict their use to a study population and then follow them for 20 years to see if they did better than the people using NPH and R. But a lot of people don’t want to wait.

It’s a matter of balancing risks and benefits, and we all need to become informed and make some of these decisions ourselves.

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Also, it seems that the system would depend on pharmaceutical companies behaving ethically upon learning about side effects.

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I know you are not condoning things, Gretchen. And upon reading my post now in the morning I realize it does come across as a bit of an infantile rant.

Still, it seems to me that, when it’s people’s lives on one side of the scale, I have a hard time finding what could be worth having on the other side, that would be justifiable: I guess this is what very big pharma decisions come down to…

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Manny, I didn’t think it was a rant. But I think we all want the impossible. We want the very best health care, with expensive MRIs and things like that, but we don’t want our insurance rates to go up. We want our drugs to be safe, but we want them to be available tomorrow, and cheap. Etc. etc.

If we’d stop spending billions and billions of dollars on defense and killing people in wars, we could afford all that. Unfortunately, our leaders seem more interested in power than in keeping us healthy.

What would be on the other side of testing every drug for CVD risks would be waiting for 10 or 20 years until the people in the test started dying of heart attacks.

When I was in college, most people didn’t survive after a cancer diagnosis. Hodgkin’s disease was one of the first cancers they were able to cure. They used heavy radiation. More recently, they’ve discovered that the radiation they used causes damage to the heart, so the survivors are having heart attacks in their 50s. But I think I’d rather be alive with a damaged heart than dead with a perfect one.

We have to work with what we know.

What is inexcusable is the million dollar bonuses they give to Big Pharma execs and the backside covering they all do when they make mistakes. I think we should aim our wrath at that rather than the fact that some drugs turn out to have bad side effects years after they’ve been approved.