Finally, a bit of good news for Merck and Schering-Plough, which have seen their overall share of the cholesterol market decline month after month. A small study sponsored by the National Institutes of Health has found that the Zetia cholesterol pill can slow the progression of cardiovascular disease.
The findings contrast with the controversial Enhance trial, which failed to show any benefit based on a measure of the carotid artery in the neck (back story). The results, which spurred congresional investigations due to handling of the clinical trial data, prompted docs to write fewer scrips for Zetia, as well as Vytorin, which combines Zetia and Zocor and insurers to change formulary status (back story).
The study, which was published by the Journal of the American College of Cardiology (here is the abstract), appears to support the argument by Merck and Schering-Plough that Enhance was insufficient for determining whether their drugs were truly effective, although it remains unclear whether the meds can reduce heart attacks risks. "The SANDS (Stop Atherosclerosis in Native Diabetics Study) Study provides (the drugmakers) with some ammunition in their efforts to rebuild their cholesterol franchise," Credit Suisse analyst Catherine Arnold writes in an investor note today.
The study analyzed 223 Native Americans with Type 2 diabetes whose LDL cholesterols were brought down to an agressively low level and found a reduction in the thickness of the carotid artery. Nearly all of the patients were given statins, but 69 also received because they couldn't reach the target on a statin alone. "Notably, those patients who needed Zetia were also able to obtain similar reductions in their CIMT levels as those on statins alone during the 36-month study," Arnold wrote.
"They achieved a very similar degree of regression," James Howard, a principal investigator of the study and director of the lipid treatment center at Washington Hospital Center, Washington, DC, tells The Wall Street Journal. "If we had not added ezetimibe they would have not gotten to that LDL target, and we are certain they wouldn't have gotten that degree of regression."
Howard, by the way, receives grants and speaking fees from Merck and Schering-Plough among other drugmakers. The Zetia analysis, the Journal notes, wasn't planned as part of an original study and was done after the Enhance trial was released.
Such a post-hoc analysis isn't as reliable statistically as one specified at the beginning of a study, according to Steve Nissen, chief of cardiovascular medicine at the Cleveland Clinic, who has cautioned against using Zetia and Vytorin. He tells the paper the number of patients on Zetia in the study was too small to detect a meaningful difference, nor was getting the Zetia based on randomization.
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"Such a post-hoc analysis isn't as reliable statistically as one specified at the beginning of a study. Steven Nissen, chief of cardiovascular medicine at the Cleveland Clinic and a prominent critic of Zetia and Vytorin, said the number of patients on Zetia in the study was too small to detect a meaningful difference, nor was getting the Zetia based on randomization. 'It's not a particularly useful analysis,' he said."
I agree with Dr. Nissen. This analysis just doesn't tell us anything, and it certainly doesn't trump the results of ENHANCE.
Just a point of clarification: what was being measured here, the thickness of the carotid artery, is a way of measuring atherosclerosis, not heart disease. Atherosclerosis can lead to heart disease but the two terms do not mean the same thing.
Marilyn
SANDS is old news - rehashed and analyzed post-hoc. Let's see, 69 patients received Zetia in addition to a statin in this study vs. several hundred in ENHANCE. ENHANCE was designed as the definitive trial while SANDS is a multi-factorial study aggressively treating hypertension and high choleterol in diabetics. Which study is the better study. I'd say ENHANCE, which was negative. I still wouldn't trust Zetia and I certainly don't trust Merck and Schering-plough, nor the author of the paper who certainly is not free of conflict.
Desperate times call for desperate measures. Like having one of your old buddies do a post-hoc analysis and publish a paper on the results. How relevant are these results, given the fiascos around ENHANCE, SEAS, Vytorin and Zetia over the past year or so?
Say what??? The King of Post-Hoc Analyses (Dr. Steve Nissen) who routinely uses these types of studies to take products down, now says they aren't "as reliable"? I suspect that the folks who work on Avandia and some other products will be happy to hear Dr. Nissen's new perspective.
PHA,
Re: Post Hoc Analyses
What the heck do you think FDA does when it does safety analyses for drug approvals or taking drugs off the market?
By your standards it's almost impossible to claim that any (even labeled) side effect is related to a drug.
Steven Nissen, chief of cardiovascular medicine at the Cleveland Clinic and a prominent critic of Zetia and Vytorin, said the number of patients on Zetia in the study was too small to detect a meaningful difference, nor was getting the Zetia based on randomization.
...I acknowledge this is a posthoc. However, assuming the variation is the same in this analysis and ENHANCE, the SMALLER the study the LARGER the difference needs to be to detect a significant difference.
Steve Nissen is a controversial "Ass Clown" who is in the pockets of Pfizer and AStrazeneca right now...the ENHANCE trial was a shit poor designed trial, taking patients who had already been agreesively treated on statins and with "NORMAL" Coratid Intima Thickness...then add Vytorin to see if they reduced the CIMT even more...it was like giving antibiotics to someone who does not have a beacterial infection...Null Results!...whenever it's good for Nissen, he makes up he opinion to whatever suits his needs...the press runs which his biased and tilted opinions...the fact of the matter is the plaque regression is a class effect..get the LDL-C down to 70 or 50 and you will stop plaque progression and even get regression...all other factors being controlled, like diabetes, hypertension, etc...to bash VYtorin tis year because of crappy ENHANCE study is a shame...it is a good product just like Lipitor, Crestor and Zetia are...ask any doctor who combines Zetia with Crestor or Lipitor and you will hear of phenomenal results in LDL Reduction...and please don't start with plietropic pixie dust effects of high dose statins...that has not been convincingly proven...at the end of the day, the LDL Hypothesis still stands...THE LOWER THE BETTER!...then go on to treating HDL and Trigs...
JD, I agree with your outlook, especially the pleitropic bs. What is your background?
Total cholesterol lovering and separate LDL components I miss in the report. Has any study done to determine conclusively which part of the statin's effect could be responsible for plaque regression? Statins certainly lower cholesterol and I read some claim stating: "the lower the better as less cholesterol will be available to be oxidized". How came people die of heart disease and stroke with perfect (arbitrary) cholesterol levels? Lately statin's anti-inflammatory effects recognized (on par with aspirin though) and CRP inflammatory marker to be tested for is recommended, I daresay only oxidized cholesterol becomes part of plaques and reducing sub clinical inflammation certainly slow progression and at some point may allow regression. There are natural alternatives i.e. antioxidants and anti-inflammatories that outperform statins and with no dangerous side effects. Big Pharma is not interested in health so won't sponsor a trial to determine the above. We need to find some private benefactors who would step up to the plate and finance such trials. Statins are aggressively being promoted and nowadays recklessly so for anything they can think of since not only the public but doctors and cardiologists are ignorant and lead by the nose, they accept what they are told on faith! I sense the days of statins are numbered, hence the pull out all stops to promote the lie.
Thanks for sharing your experiences regarding this trial.I really appreciate the efforts you have made for this article.Zetia is taken orally in conjunction with a statin drug and aids in lowering low-density lipoprotein (LDL) in the blood. It specifically acts at level of the brush border of the small intestine by preventing the absorption of cholesterol into the bloodstream.but it should be avoided if You have liver disease,you have demonstrated a previous allergy to ezetimibe and you are nursing or are pregnant.ZETIA works in the digestive tract, as do some other cholesterol-lowering medicines.
Quite an interesting study, indeed. Hope the end results will be great. Thanks for sharing.