Vitamin Beats Statin: Is Merck's Zetia in Trouble?

A small study is causing a big splash in the multi-billion dollar world of cholesterol treatments. The test, pitting a prescription form of the B vitamin niacin against the prescription drug ezetimibe, found that niacin significantly shrank artery walls when taken in combination with a statin. The commercial version of ezetimibe by contrast, sold by Merck (MRK) as Zetia, showed no measurable change in arterial plaque build-up. That result could give doctors pause for thought and has already created a stir among Merck investors concerned about the study’s impact on already-declining Zetia sales.

The study, led by Allen Taylor, director of the Advanced Cardiovascular Imaging and the Lipid/Prevention Clinic in the Department of Medicine at Washington Hospital Center in Washington, D.C., was presented at the American Heart Association’s Scientific Sessions 2009 and simultaneously published in The New England Journal of Medicine. Taylor and his colleagues conclude that the “the use of extended-release niacin causes a significant regression of carotid intima–media thickness when combined with a statin and that niacin is superior to ezetimibe.”

A second, larger study that relied on medical records collected by UnitedHealth Group found “no significant differences in cardiovascular outcomes when comparing the effectiveness of ezetimibe/simvastatin to equipotent doses of (the statins) simvastatin or atorvastatin alone.” Its results were presented in the Heart Association’s scientific sessions as well.

Merck Research Laboratories president, Peter Kim, defended Zetia, saying that "the results of the small ... study (called Arbiter 6) do not, in any way, change our view of Zetia and Vytorin as effective medicines for fighting high LDL cholesterol." The company also questioned the rigor and size of the 208-person study, suggesting it couldn’t provide “meaningful insight into the effect of either niacin or ezetimibe on clinical outcomes.”

Taylor’s study follows negative attention Vytorin received in 2008 after two studies questioned Vytorin effectiveness and safety when compared to the use of the statin simvastatin alone.

Comments

[notsosmart]

my dr took me off zetia mos ago. niacin did not do anything for me. the statins did.

2009 Nov 20 08:28 PM

[generic internist]

"vitamin beats statin"? Started wrong footed, Zetia is not a statin, but then again Zetia is looking more wrong footed after sequential failure to show benefit in Arbiter6, Seas and Enhance trials.

Significantly the trend is toward harmful events in the Zetia arm of the Arbiter study. The study is small, but cannot be ignored as a possible early signal of harm. Zetia and Vytorin can no longer be used in a casual fashion as initial therapy.

2009 Nov 20 11:00 PM

[ncalmd]

generic internist: I rarely see anyone taking Zetia that is tolerant to statins, except for "poor responders" to statins. That's why I think the drop in use of Zetia may be less than might be expected. I've encountered very few patients who are willing to stay on Niaspan, due to combination cost side-effects. I just don't think that trend toward harm was/is significant enough to stop zetia for most patients when there aren't other decent choices. On the other hand, if another non-statin shows that drops LDL 25% or so, then I see zetia use falling off a cliff.

2009 Nov 21 01:12 AM

[generic internist]

thnks for reply, ncalmd. On the other coast I see more initial rx with vytorin, which should be reconsidered. I was quite surprised Mrk was actually starting to generally promote Zetia for initial rx (just before Enhance trial fiasco), not just for the statin intolerant.

I was also concerned that the patients in Arbiter 6 with greatest LDL reduction on Zetia, had greater plaque progression, suggesting unintended impaired reverse cholesterol transport.

Needless to say, I stopped using Zetia myself, on Monday, having used statin/Niaspan/Zetia combo for myself for primary prevention for several years. It will be interesting to see if I can show plaque regression in my triple therapy patients, after stopping Zetia

2009 Nov 21 08:29 PM

[auto44]

I had to stop taking niaspan due to the cost. I fell into the doughnut hole, A lot of money for supedup niacin.

2009 Nov 21 08:39 PM

[ncalmd]

genericinternist: interesting that prescribing patterns differ to that degree, but that might be due to the fact that for all practical purposes, only three insurance companies have controlled the market in California for many years. They have made it so time consuming for the physicians and staff to obtain pre-approval for zetia (and many other non generics), that nobody gets put on Zetia casually. So I am probably wrong in assuming that the drop in zetia sales will be minimal, if zetia is used far more casually in other parts of the country.

2009 Nov 22 12:41 AM

[The Rogue]

I would trust NOTHING coming out of Johns Hopkins, and here's why: adventuresincardiology.../

2009 Nov 22 09:08 AM

[ncalmd]

therogue: I read the link you gave, and unfortunately I can't tell from that article what happened. What I can tell you, is that if the wrong catheter was used, or if the catheter was put in the wrong way and the patient was injured, Hopkins would have made a settlement offer. Contrary to public perception, every bad outcome in a hospital is reviewed by at least two different physician committees. I've served on many of these committee's and there is never any attempt to cover or hide the facts, in fact quite the contrary. It really doesn't take any altruism on the part of physicians, because if an attorney can find even the slightest hint of an attempted coverup, the malpractice award will go through the roof!

2009 Nov 22 04:57 PM

[generic internist]

Ncalmd, I just confirmed tonight, the formulary for Coventry and Southern Health still list Vytorin as tier 2 and Lipitor tier 3.

This makes no medical or scientific sense. Based on Arbiter 6, we now have more reason to suspect these perverse patient financial incentives may put lives in jeopardy.

I am not sure what goes on behind the closed doors of contracts between the insurance company and major pharmaceutical companies. Perhaps we have ceded too much power to the insurance industry and their pharmacy benefits managers.

Unfortunately, the major focus of telephone calls and office visits is beginning to be diverted into these formulary issues in an increasing number of my patients.

2009 Nov 22 09:51 PM

[ncalmd]

genericinternist: I hadn't really given any thought to where Zetia or Vytorin fell in the tier levels, as I only used Vytorin, when someone couldn't reach goal on maximum dose of the other statins. While I was never thrilled about jumping through the endless hoops to have a PBM approve Zetia in my non responders, I didn't have any great problem with PBMs being reluctant to pay for Zetia, since Zetia had never been shown to decrease event rate. But to make Vytorin cheaper than Lipitor or Crestor would seem to put the PBM and insurance company at risk if a patient had an event on Vytorin. Unlike simvistatin, Lipitor and Crestor where its reasonable to assume the event rates should be similar for similar levels of LDL reduction, this was never a reasonable presumption with Vytorin.

2009 Nov 23 12:37 AM