The counteroffensive is gaining steam. Last night, the American College of Cardiology issued a statement urging docs and patients not to panic over the results of the controversial Vytorin trial released - two years late - by Merck and Schering-Plough, and the widely publicized remarks by the Cleveland Clinic's Steve Nissen that Vytorin (and Zetia, which is one-half of the med) should be used only as a last resort. The trial compared Vytorin with Zocor, the other drug in the combo.
This morning, the American Heart Association issues a similar statement, prompting Tim Anderson, an analyst at Sanford Bernstein, to write that "the two biggest organizations representing cardiovascular medicine have now weighed in on the matter, in support of Vytorin. This should help to quell the hysteria around Enhance results, which have been blown out of proportion in our view." Separately, Congress will still probe the delay and the reasons why the primary endpoint was, briefly, changed.
The AHA statement notes that the Enhance trial found the combo was no more effective in reducing artery plaque build-up than Zocor alone....but "there were no statistically significant differences in the safety of the drugs, which are used to lower cholesterol...and the LDL levels in both groups remained well above target level."
Plaque build-up (atherosclerosis) in the arteries can lead to coronary heart disease or stroke, the AHA statement continues. However, the study was not large enough or long enough to determine whether the combination drug is more or less effective than the single drug in reducing heart attacks or deaths, the AHA argues. Because high cholesterol levels are a very important risk factor for coronary heart disease, the AHA urges patients to consult with their physician before changing or stopping any medication treatment.
“It will be very important for those larger studies, directed at assessing cardiac outcomes, to be completed, so we can fairly assess the potential of (Vytorin),†says AHA president Dan Jones, in the statement. “Because Vytorin does not appear to be unsafe, lipid-lowering therapy with (Zocor) is of proven benefit, and some patients have been prescribed Vytorin, because a statin alone may not have been sufficiently effective in lowering their LDL or was not appropriate for them because of other medical conditions, we do not believe patients should stop taking the drug on their own,†says Jones.
15 Comments
Talk about "panic" and "hysteria" misses the point.
As has been reiterated here, it's not about the drug - at least at this point. It's about the handling of the study by MSP.
Every time it looks like a company is about to take a solid step forward it finds a new way to shoot itself in the foot.
Vytoin/Zetia isn't unsafe -it's just useless and a waste of money!
Agreed - one point is definitely about how/when the study was interpereted and communicated. But "panic and hysteria" are certainly important points too. This time it was a cholesterol drug - okay, chances are nobody's going to be harmed (at least for a while) because they stopped taking their Vytorin after watching the 6 o'clock news. Let's hope that when the next episode of on-air punditry occurs, it doesn't involve a drug that's used for seizures, asthma, or other condition where the consequences of discontinuation could be far more serious.
AHA statement no doubt bought and paid for by Merck and Schering-Plough. Guess who sits on the elite AHA pharma board? You got it! Guess how much it costs? Minimum $100,000! It's like being a member of Augusta National and having your say with the position of the golf club. The FAVOR had to be called in. Money talks!! Once agaain, the AHA should disclose their financial ties as well as the people that wrote the response.
As stated above, it's not about whether or not the drug lowers cholesterol. It's about whether or not the price of the drug is worth it. And it's also about how this fiasco was handled by the leaders of Merck and Schering-Plough. The answer is very poorly!!
You got it! I think now Congress needs to investigate the AHA and the ACC so all can see how dirty their hands are. These Big Pharma companies are disgusting! They throw around money that they make from the public as if it was water. There needs to be a divorce between Big Pharma and medical and scientific organizations.
I don't think that divorce should be limited to big pharma
This really pisses me off......I have been counting on the doctors to give me the best possible solution for my hereditary high cholesterol problem and now this happens way after they knew better......what the heck! Who can we trust?........this is an example of how money making gets in the way of doing the right thing....I am just another sucker.
There is little doubt that the AHA statement has been bought and paid for by MSP. They sit on the highest level pharma board at AHA and it's times like these that the Big Pharma "goons" call in their FAVORs to the societies. Most of the major players in these organizations have very close ties to pharma. Some of the opinion leaders make 4500,000 dolloars or more per year just from Big Pharma. The top guys get that kind of money simply as a retainer for when they're needed!
Stuff like this makes me glad I am just a regular schmo and not some guy making a living through deceit and deception. There is no price tag you can put on being able to look yourself in the mirror.
the remarks I saw on NBC were not alarming or creating hysteria. the doctor said, "don't stop taking a drug because of what you saw in a news report, check with your doctor" The company dropped the ball here and consumers are paying for it with there pocket books.
[...] PharmaLot: AHA Counteroffensive - Vytorin isn’t “Unsafe” [...]
A little more debate on the science side of these results can be found here:
http://pipeline.corante.com/archives/2008/01/14/vytorin_holed_under_the_waterline.php#comments
All this hysteria is a little silly. Both drugs work -- they do exactly what the manufacturer says that they should: They lower cholesterol. In fact, as would be expected, Vytorin lowers cholesterol more than Zetia.
The problem is that doctors have always said that lowering cholesterol should lead to a reduction in arterial plaque. As expected, both medications reduced arterial plaque. However, the problem is simply that an additional decrease in cholesterol (with Vytorin) did NOT lead to additional decreases in plaque. It will probably be years before we know why.
This doesn't mean either drug is unsafe. In fact, both drugs are effective. The only problem (for Merck) is the fact that Vytorin is not MORE effective than Zetia. (as well, of course, as the controversy around the clinical trial endpoints)
One other point: As pointed out in Ed's article, this was a relatively small clinical trial -- so heart attack risk could not be measured. It is entirely possible after all this that a larger clinical trial will show that there IS a benefit to Vytorin when looking a heart attacks as the primary endpoint. Moreover, from what I understand, this clinical trial enrolled only people that already had VERY high cholesterol. This was not a trial that looked at your average overweight American with a cholesterol level of 230 or so. Entirely different results might be obtained by looking at a more "typical" patient.
I think that the big point is being missed here. Ezetimibe works to lowere cholesterol and may very well turn out to be a beneficial drug. The companies and their top management completely blew it. If they would have done the responsible thing and let it be known early on that there were some problems with the data, things would be fine. Instead, they held onto it for probably about 18 months too long, permitted some of their top executives to sell off their stock at a huge profit, and now are suffering for their deeds. Patients shouldn't worry about taking ezetimibe to lower their cholesterol, but they and the Congress should worry about the incestuous relationships between Big Pharma, the Key Opinion Leaders at our top academic institutions, and the major medical societies in this country.
More about conflicts of interest affecting the AHA statement can be found on Health Care Renewal here: http://hcrenewal.blogspot.com/2008/01/why-should-patients-continue-to-take.html
BACKPEDDLE Century!!! Wow, if the results of the trial were positive, we would have heard about what a landmark trial this was. Instead, now all of a sudden:
"There were too few patients to change prescribing...it wasn't long enough...we needed more time" Give me an absolute break. Who do they think they are kidding? One of the main reasons imaging studies such as ENHANCE are done is b/c they are strong predictors of CV events and you don't need 5,000 patients and 5+ years to prove the product's benefit. For a carotid artery study such as ENHANCE, all MSP needed was ~300 patients and 18-24 months. They had 720 patients, more than double the patients needed to effectively power this study, and 24 months!
Not convinced? Try to google ASAP, ARBITER, REVERSAL, or ASTEROID. These are all medically sound, landmark imaging studies with 200 - 700 patients, ranging 12-24 months!!! Mainstream doctors find these studies to be reliable so why should ENHANCE suddenly fit a different category?
Is 720 still not a big enough number? Then let's visit the number of images "they had to collect." And I write it that way b/c that is how they portrayed it. Remember the excuse as to why they were not releasing the data? They just had way too many images to collect and they were not prepared for it? Try around 30,000 images. Can a reasonable conclusion be drawn from the objective, hard evidence that lies in 30,000 images? Again, this is why imaging studies do not require a high number to be powered.
"The patients in our trial were too sick." Again, google ASAP...same patient type, same LDL levels. Trial showed a difference in treament arms. 1/2 the number of patients. Also two years. Next.
Who funded the study??? Ahhhh, let me think....oh that's right, MSP did. The makers of Vytorin. Are people losing sight of the fact that they conceived the trial as a future confidence statement? Look how great we are vs. straight Simvastatin! They don't get the results they want and now follow the excuses of the study's weaknesses. Boring and predictable.
As far as the ACC/AHA statements go, suggesting doctors not to panic and change patients based on this study...they are right. There is no need to panic and switch all of their patients overnight vs. casually as the patients cycle through regular office appointment. Again, "Vytorin is not un-safe"...their new marketing phrase.
Regarding AHA's backing of the "too few patients / not long enough" theory. They should be ashamed of themselves because they know better. Read USA today from Thurs, Jan 17. They even know what is needed to effectively power an imaging trial. Again ~300 fits the bill, let alone 720 with two years worth of images.
Regarding MSP or even ACC's suggestion to wait for the heart attack / stroke studies to be completed: How legit will that study be given that the study's patients are already dropping out officially or unofficially due to ENHANCE and the media hype?
Why wait for that data to be completed when there is amazing heart attack and stroke data already out spreading across Pravachol (generic), Simvastatin (generic), and Lipitor which will be generic by the time Vytorin has it's data we should all so excitedly wait around for.
HIPOCRITIC ACC's "major clinical decisions should not be made on the basis of enhance alone"...to me, a major clinical decision is switching a patient from Vytorin to a straight statin based on ENHANCE. Sounds to me like they are suggesting not to change anyone or anything until the "real" data is out in 2-3 years... Lean in for this one... AHA/ACC Guidelines for Secondary Prevention: Journal of the American College of Cardiology (May 16, 2006 Volume 47, No 10, Page 2133)..."The writing group emphasizes the importance of giving consideration to the use of CV medications that have been proven in randomized clinical trials to be of benefit. This strengthens the evidence-based foundation for therapeutic application of these guidelines." What are AHA/ACC suggesting in their latest ENHANCE release? Sounds like they need to get their story straight.
Am I the only one not seeing the dilemma here? Vytorin was approved by the FDA on the "Me too" notion that is also lowers cholestrol and makes the lipid panel look great on paper, therefore it must provide benefit. Now we know it doesn't provide anymore benefit than the common, generic Simvastatin. In the meantime, many statin drugs both generic and branded (Simvastatin / Lipitor) do have great data NOW! No need to wait 2-3 years to find out that they look good on paper and actually do their real job, reducing heart attacks and strokes!