Comments on: The Vytorin Anomaly: ‘You’ve Got To Be Worried’

By: Marilyn Mann

Marilyn Mann — Tue, 19 Aug 2008 00:27:24 +0000

There is a possible way ezetimibe might increase cancer risk, discussed August 11 on Gooznews. Ezetimibe reduces absorption of plant sterols, aka phytosterols. Plant sterols are thought to have anticancer properties. By lowering blood levels of plant sterols in the treatment group, ezetimibe may have increased cancer risk.

By: SP 2

SP 2 — Mon, 04 Aug 2008 16:51:18 +0000

Davidson is in SP’s back pocket! Everything he says must be taken with a grain of salt. Any patient who takes ezetimibe after hearing about SEAS is playing Russian roulette with their body. The results were statistically significant and cannot simply be dismissed as “occurring by chance.” That’s why statistics exist!!!!

By: Piper

Piper — Wed, 30 Jul 2008 21:47:21 +0000

For a more informed take on ENHANCE, vs. Dr. Taylor’s editorial in the CCJ, I recommend Dr. Davidson’s recent write-up, which can also be found in this month’s CCJ: http://www.ccjm.org/ccjm_pdfs_toc/July08_Davidson.pdf

By: Jack2

Jack2 — Tue, 29 Jul 2008 18:23:33 +0000

FPME in a RANDOMIZED, PLACEBO-CONTROLLED trial you don’t A) worry about the lifestyle of patients going into the trial because the study was randomized*, and B) you don’t need to check if the risk was “above what we [sic] the normal population of incidence of cancer” because the trial was placebo-controlled - you just need to compare to the placebo-group - that’s why they’re there. You did work in pharma right?

Merck and SP - did your stats correct for multiplicity? I’d also say JiM makes a good point - clearly it is a signal.

*After the trials done, you do double-check the demographics of both groups to make sure your randomization was good - and both populations were equal.

By: Practicing Doc

Practicing Doc — Tue, 29 Jul 2008 15:02:16 +0000

The cancer findings in SEAS are what they are. From the data I’ve seen reported, the findings met significance from a statistical point of view (p<0.05). It’s very troubling that MSP is seeking to wash this away with a letter stating their interpretation of the finding. We know that statins have CV benefits. We don’t know if Zetia (or the addition of it to simvastatin in Vytorin) does anything beneficial for morbidity or mortality. I’m not using it until I see good data from IMPROVE-IT.

By: Marilyn Mann

Marilyn Mann — Tue, 29 Jul 2008 14:52:08 +0000

Another link to Condor’s blog — he imbedded the videos of the debate between Drs. Taylor and Stein:

http://shearlingsplowed.blogspot.com/2008/07/of-rough-seas-and-mcluhans-you-know.html

I recommend this editorial by Dr. Taylor in the July Cleveland Clinic Journal of Medicine:

http://www.ccjm.org/ccjm_pdfs_toc/July08_Taylor.pdf

By: Justice in MI

Justice in MI — Tue, 29 Jul 2008 02:52:44 +0000

Many thanks, Marilyn - That clarifies a good deal for me.

By: Marilyn Mann

Marilyn Mann — Tue, 29 Jul 2008 01:52:22 +0000

Hi Justice in Michigan,

I can give the general concept of what Dr. Liao means. Statins inhibit HMG-CoA reductase which causes less cholesterol to be synthesized by the body. This is part of the mevalonate pathway which also produces something called Rho-kinase, which has inflammatory vascular effects. By inhibiting HMG-CoA reductase, statins also decrease production of Rho-kinase.
When ezetimibe decreases cholesterol absorption, that causes the body to synthesize more cholesterol to try to make up for it. HMG-CoA reductase activity increases, which causes Rho-kinase to increase. So ezetimibe counteracts some of the antiinflammatory effects of statins. Hope that helps.
For a recent review article, see Chao-Yung Wang, Ping-Yen Liu and James K. Liao, Pleiotropic effects of statin therapy: molecular mechanisms and clinical results, Trends in Molecular Medicine, Vol. 14, Issue 1, January 2008, pages 37-44.

By: Former pharma Marketing Exec

Former pharma Marketing Exec — Mon, 28 Jul 2008 13:41:38 +0000

What’s missing in the studies for Vytorin is the information that is needed about the patient population in detail. What are their life styles, where to they live? Do we know for certain that any of the cancers that developed while on Vytorin were not present beforehand? No, we don’t know because for many of them we do not even have bio markers to effectively test if they are present. After the fact, is there or was there any bio material from the patient/subjects in the clinical trial to go back and do DNA and epigenetic analysis? I haven’t read if any of this was done.

Right now all we can say is there was an increase in cancer that was above what we the normal population of incidence of cancer.

What percentage of the patients in the studies had high cholesterol due to genetics rather than poor health habits? It is becoming more and more evident that poor nutrition habits and poor exercise habits lead to higher incidences of cancer. Patients with high cholesterol, unless it is genetic are at a higher risk for cancer already.

What is really distrurbing is that both Merck and SP want to send out letters essentially “blowing off” the cancer incidence data. That is unacceptable and completely unethical in my view, because we haven’t established why this is occurring.

So, we have a drug that hasn’t really shown any benefit to do what it was originally designed to do, and a higher incidence in cancer in the patient subjects who took it.

That people are being asked to “overlook” these important facts is just plain wrong.

Ther perfect storm!!!

By: Justice in MI

Justice in MI — Sun, 27 Jul 2008 22:59:28 +0000

Thanks for the Forbes reference, Marilyn. I was especially curious about this bit:

“But Liao argues that Zetia might actually make this inflammation worse and therefore may have less benefit at preventing heart attacks or even, theoretically, cause some harm.”

Elsewhere in Matt’s piece, it says that crp appears to be reduced by adding zetia. Do you or anyone have speculations about by what mechanism zetia might act to increase inflammation?

Thanks for anyone’s thoughts.