Monday, July 28, 2008

Of Rough SEAS -- And McLuhan's "You know nothing of my work. . . ." scene


[UPDATED -- 07.29.08 @ Noon EDT: The Insider, over at PharmaGossip, has named this blog (presumably, on the strength of the below-post), a "hot blog"! Cool!]

This feels a little like the scene in the movie "Annie Hall" -- where Woody Allen pulls Marshall McLuhan, almost bodily, from behind a cut-out [A Real-audio stream of that moment!], to suggest that a near-by bloviating know-it-all, in the ticket-line at the movies -- really. . . . doesn't -- Ahh, but "What the heck?", here goes:



Slide it forward, to the 2:05 mark in the clip! He~He!


You'll need to read my post quoting Dr. Harlan Krumholz (the noted-cardiovascular authority, of Yale University Medical School), of this past-Friday, for this to make the most sense -- but on those SEAS-related cancer incidence observations, the following took place, in the comment-box connected to that post, over the weekend. I think it deserves a much wider audience -- so I re-print it now, as its own post.
Anonymous said...

Krumholtz [sic], 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 [sic].

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.

July 26, 2008 4:35 PM


~~~~~~~~~~~~~~~

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.

July 26, 2008 5:47 PM


~~~~~~~~~~~~~~~

Anonymous said...

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.

July 26, 2008 6:08 PM

~~~~~~~~~~~~~~~

Marilyn said...

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

July 27, 2008 7:40 AM


~~~~~~~~~~~~~~~

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

July 27, 2008 8:04 AM


~~~~~~~~~~~~~~~

On ENHANCE:

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

Also, on MedPage Today:

Researchers Debate Ezetimibe/Simvastatin (Vytorin) ENHANCE Trial, Parts 1, 2 and 3:








Indeed. Do follow the links.

No comments: