"For one thing, ENHANCE was not a clinical-end-point trial, as was reported in the media, nor were the results "negative," said Greenland. They were not statistically significant, a big difference lost among some in the media. Moreover, the end point was not "fatty plaque," as reported by others, but intima-media thickness. More concerning, however, was the fact that ENHANCE "mushroomed" to the point where almost 50 years of "serious and logical research has been damaged and defamed for no good purpose," write Greenland and Lloyd-Jones."
http://www.theheart.org/viewArticle.do?primaryKey=845925&nl_id=tho04mar08
Vytorin / Zetia should be pulled until it can be shown to be safe.
18 months off the market will encourage MDs to prescribe super low doses of STATINS, say 10mg of Atorvastatin, or low dose Lovastatin (easily tolerated). Any statin is likely much much better than any dose of V / Z. If a case can be made for using it after failing 3 statins ... maybe it could be let back on the market.
I promise never to prescribe it. I'd definitely resort to a placebo pill before ezetimibe.
================
No Benefit. - http://heartdisease.about.com/b/2008/01/14/enhance-at-best-no-benefit-from-vytorin-or-zetia.htmPatients in the trial who took the combination of Zetia and Zocor were receiving it in the form of Vytorin pills. The trial, called Enhance, lasted two years and covered about 720 patients with extremely high cholesterol, mostly in the Netherlands.Dr. Steven Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.” Patients should not be prescribed Zetia unless all other cholesterol drugs have failed, he said.“This is as bad a result for the drug as anybody could have feared,” Dr. Nissen said. Millions of patients may be taking a drug that has no benefits for them, raising their risk of heart attacks and exposing them to potential side effects, he said.
from http://www.nytimes.com/2008/01/14/business/14cnd-drug.html?_r=3&ref=health&oref=slogin&oref=login&oref=slogin
Users of the prescription cholesterol medicine Zetia and Vytorin received some troubling news from the makers of the drug today: Although the pills they’re taking lower their cholesterol, there is no evidence that they reduce the risk of heart attacks and strokes, and may, in fact, be putting them at risk.
We first warned against using Vytorin, a combination of Zetia and the cholesterol drug Zocor (now generically available as simvastatin), in December 2004 on our Web site, WorstPills.org. At the time, we said that people should wait at least seven years before taking this new drug, considering that Vytorin wasn’t a “breakthrough” drug, which offers a documented advantage over older, proven drugs.
I'd like to do a study that proves a doctor following Public Citizen is likely to be a better prescriber than one reading the increasingly bastardized medical journals.
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The most important rule here is this.
The Health Research Group’s Seven Year Rule
You should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs.
http://www.pharmalot.com/2007/12/the-vytorin-clock-tells-you-when-to-hide-data/
Here we have a lovely addition to any office or living room. A smart design enhanced by bold colors. And so useful - the clock can tell you when to start a Vytorin study; when to avoid listing the study at clinicaltrials.gov; when to deny lead investigators access to the database; when to worry about results that confound expectations; when to change the primary endpoint; when to establish a secret panel of experts to review data, and when to backpedal due to congressional scrutiny and bad publicity. Unfortunately, there is one thing this sleek, battery-powered model is unable to do - tell you when to exercise good judgment and act responsibly.
DrMurdoch: The Health Research Group’s Seven Year Rule You should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs.
DrMurdoch:We first warned against using Vytorin, a combination of Zetia and the cholesterol drug Zocor (now generically available as simvastatin), in December 2004 on our Web site, WorstPills.org. At the time, we said that people should wait at least seven years before taking this new drug, considering that Vytorin wasn’t a “breakthrough” drug, which offers a documented advantage over older, proven drugs.
Even a broken clock is right twice a day. WorstPills.org seems like one of those broken clocks, to me. They throw a lot of stuff at the wall, and when something sticks they say "look what we figured out before anyone else."
The seven year rule...really...I presume you really feel that such a rule is practical.
I believe that it would bring drug research to a grinding halt, and I don't think that you would mind.
In a world overflowing the bullshit, it's nice to read something written by someone straight-shooting.
Albeit, rare.
I think at best, Estemibe does nothing. An expensive, non-endpoint altering scam.
At worst, I think it harms.
Everyone should read this :
http://scientific-misconduct.blogspot.com/2007/11/ezetimibe-zetia-vytorin-small-of-bad.html
The main question is this:
Why make your patients swallow pills that have not been shown to work ?
and
Might be harmful ?
The company is committing fraud and is not playing fair with scientific research ?
...
rheumdoc: I believe that it would bring drug research to a grinding halt, and I don't think that you would mind.
Au Contraire mon ami,
It would encourage drug companies to make NEW BREAKTHROUGH drugs, not just "Me Too" drugs.
I am not sure what you are supporting .... you think it's OK that drugs with no benefit are good ? If the pharma industry is all about producing ezetimibe .. then maybe it should fail. I think there are enough drugs already ... it's time that new drugs meet higher standards.
I must admit Sidney Wolfe and Public Citizen have helped me avoid the bad drugs.
Drug Companies, FDA Lagged in Warning Public About Zetia, Vytorin Jan. 14, 2008
http://www.worstpills.org/public/page.cfm?op_id=78
Richard Harris, editor of the Lancet says there might not be many new breakthrough drugs out there. If that is the case duping doctors into drugs like Zetia will be the future.
WHAT? Sidney Wolfe? Nissen too i suppose. Wow. This is a losing battle.
Why even bother reviewing clinical data, or even learn to read how to interpret all these, just read what they say and take their word for it.
I think you are missing the point on the original article I posted here.
Study investigators, led by Dr John Kastelein (Academic Medical Center, Amsterdam, the Netherlands), tested the effectiveness
http://www.theheart.org/viewArticle.do?primaryKey=851409&nl_id=tho30mar08
Roger, as long as you stop probably 90% of your current Ezetimibe prescriptions, you should be OK.
"There is little in ENHANCE that is in the drug's favor, and I don't know if there's anything," Dr Harlan Krumholz (Yale University School of Medicine, New Haven, CT), who was not affiliated with the study but is part of an ACC panel discussing the trial, told heartwire. "There isn't much new in the study either, but it does give us a chance to take a deep breath and recognize how little we know about the real effect of this drug on people. However, I think to say we should keep doing what we're doing until the clinical trials come out is a problem."
I've still never prescribed this stuff. Likely never will. For my vasculopaths to be, I try statins, starting with atorvastatin.
For anyone else that wants to read the article,
Username: Lamelame
Pass: lamelame
The TI chaps weighed in on ezetimibe.
http://www.ti.ubc.ca/en/node/185
There are sadistic scientists who hurry to hunt down errors instead of establishing the truth. Marie Curie
Let's wait for the IMPROVE IT trial before tossing out Ezetimibe. I am surprised the unachieved goal numbers were not utilized as an issue. I am also disappointed that at 2 years a final verdict have been made regarding the drug.
Cholesterol Lowering and Ezetimibe: http://content.nejm.org/cgi/content/full/NEJMe0801842?query=TOC
Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe?: http://content.nejm.org/cgi/content/full/NEJMe0801608?query=TOC
Rogerven: Let's wait for the IMPROVE IT trial before tossing out Ezetimibe. I
Let's wait for the IMPROVE IT trial before tossing out Ezetimibe. I
I feel the prudent path is to stop Ezetimibe now and titrate up their statins, if needed.
Waiting 2 years is too long ?
Rogerven: Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe?: http://content.nejm.org/cgi/content/full/NEJMe0801608?query=TOC
This is an expert opinion letter.
In the meantime, the thoughtful clinician may elect to adopt the following reasonably cautious strategy, which is similar to that recommended in the January 15 statement of the American College of Cardiology17:
Pre Step 1- Realize that lipids are just one aspect of the bio-psycho-social aspects of CardioVascular Health.
(1) First, achieve targets for levels of LDL and HDL cholesterol (or of the ratio of total cholesterol to HDL cholesterol) with the use of statins
(1.5) plus drugs that have shown clinical benefits when added to statins (e.g., nicotinic acid,18,19 fibrates, and bile acid sequestrants), as tolerated.
(1.75) Make sure you have picked an appropriate lipid target for your patient.
(2) Second, use ezetimibe in patients who, despite the above-mentioned therapy, do not achieve their individual targets.
(3) And third, wait for clarifying studies.
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The vast majority of patients really never got a shot at step (1.5). To be fair to these patients, Ezetimibe should be discontinued and attempts at all three drugs classes should be undertaken first.
I suppose a rough guess would be that 5% of patients have completed steps (1), (1.5), (1.75), so only 5% of patients on Ezetimibe should remain on it until proven otherwise.
Note: I added a few steps