Friday, July 25, 2008

The more-rigorous reviews of SEAS are beginning to appear. . . .


And, the ever-on-point PM, over at Gooznews, has done a stellar job of synthesizing them -- do go read that one, top-to-bottom, but here is one money quote:

. . . ."This drug [Vytorin] does not have sufficient evidence for it to be used as a front-line agent," [Dr. Harlan Krumholz, of Yale University Medical School] said. "Statins are the drugs of choice. The evidence is not even strong enough to say that people who cannot tolerate statins should go on it. It is an option. Right now using it is based on an assumption that you know what IMPROVE-IT will find. . . ."

[Emphasis supplied.]

Gooz, himself, had written on the cancer concerns, driven by the SEAS data release, earlier in the week. Do go read it, as well.

UPDATED -- 07.26.08 @ 10 AM EDT: Ed, at Pharmalot, has also put up a similar review -- with additional, exclusive Krumholz quotes.

Also a very worthy read on the topic.

7 comments:

Anonymous said...

Krumholtz, although respected and distinguished does not reflect the entire population of opinion. He and Nissen have always been critical of more than just Vytorin and Zetia. There are many who listen to them and do the opposite, for they have created their own political storm for themselves. For Balance, refer to Thomas Dayspring who says the news is FANTASTIC. (HE SUPPLIED HIS OWN EMPHASIS.) His newsletter, Lipidaholics is up to date and his credentials are as good if not better than Krumholtz.
Remember, this population has no Tx except surgery so a Tx that offers 22% decline in events is not a bad thing. Whether the decline is due to the statin or to zetia is a good question but does not change the usefulness of this new information. The cancer incidence has been dealt with quite nicely by the experts from Oxford so I am not concerned and believe it to be unrelated to the Vytorin.
Be careful to take a completely negative opinion of SEAS. Take it in context with all other studies and advance your knowledge, not limit it. This will result in better Tx for pts and a better discussion.

Harlan Krumholz said...

I appreciate being called respected and accomplished -- I do not know Dayspring and whether he is a speaker and consultant for the companies, but I take your word that he is a good source. The people in London were also the stars of the medical world and they discounted the risk. There is controversy and people of substance on different sides of this discussion. From my perspective SEAS provided no evidence to support ezetimibe (the study was negative -- but statin trials of AS have also been -- it did have a 22% reduction in risk but that is not more than what we would have expected from simva alone -- but that is an indirect comparison -- so all we can say is no supportive evidence) -- and then a question of a cancer risk -- that was strong in SEAS but unexpected -- and then there also exists an excess risk for cancer death in IMPROVE-IT/SHARP (the P value is somewhere around 0.05 and whether it is above or below may depend on what analysis you do -- but essentially it is close to 0.05). Now there is other info that would lead one to doubt the association -- but, in my opinion, it is hard to dismiss it completely. The findings from these studies would seem to reinforce the message that people should be on statins if they can take them and get to target. And for people who cannot, many will consider ezetimibe as an option but patients and doctors should know that the safety and effectiveness has not yet been established in clinical trials.

SEAS has raised a safety issue -- many are uncertain about it, were surprised by it, and have some concern about it (that is, we do not believe the evidence from IMPROVE-IT/SHARP can dismiss it). We hope it is not a true adverse effect as 3 million people worldwide are reportedly on the drug. But patients should be aware that the issue will not be settled until more data become available.

Anonymous said...

http://www.biocritique.com/panel.cfm?groupid=a37c869a-d617-4e63-a100-5c8bfcbe2763

Thomas Dayspring, MD, F.A.C.P. has disclosed that he is on the Speaker's Bureau for Astra Zeneca, Reliant, Abbott, Merck, Schering Plough and Sanofi-Aventis and is a consultant for Abbott and Reliant.

Marilyn said...

Great article by Matt Herper on differences between statins and ezetimibe:

http://www.forbes.com/healthcare/2008/06/30/cholesterol-schering-vytorin-biz-healthcare-cx_mh_0630cholesterol.html

Anonymous said...

The webcast of the SEAS trial can be viewed at clients.mediaondemand.net/Pederson with Tedje Pederson, chairman of the SEAS study, Sir Richard Peto and Rory Collins from Oxford, Eugene Brown from Harvard, Robert Califf - Duke University.

An additional worthwhile review can be seen at the National Lipid Association - www.lipid.org where ENHANCE is reviewed in a virtual roundtable discussion, "An Examination of the ENHANCE Trial - proceedings of an expert roundtable discussion webcast" www.lipid.org/news/lipid_insight_enhance.pdf

Anonymous said...

On ENHANCE:

On theheart.org, you can see "Surrogate End Points on Trial: ENHANCE and Other Controversies"

http://www.theheart.org/article/855277.do

Also, on MedPage Today:

http://www.medpagetoday.com/Cardiology/Dyslipidemia/tb/9111

Anonymous said...

hm, the second url got cut off

Researchers Debate Ezetimibe/Simvastatin (Vytorin) ENHANCE Trial, Part 1
http://www.medpagetoday.com/
Cardiology/Dyslipidemia/tb/9111