Wednesday, February 3, 2010

Forbes' Matt Herper -- On The Vagaries Of High Cholesterol Treatment Protocols


Even though there remains some room for debate about the role of Zetia and Vytorin, and there remains uncertainty in the field overall about the desirability of treating patients to acheive numerical goals, the bell certainly seems to be tolling for the legacy Merck/Schering-Plough partnership's flagship offering: Vytorin. Especially so, at the astronomical prices New Merck expects for the drug -- a drug that no one seems comfortable saying will actually reduce heart attack risks.

It seems Forbes, and Mr. Herper, could not source a single independent and reputable expert quote -- to defend its use, as a first-line treatment. Do go read all of Mr. Herper's careful, well-researched and well-reasoned article, but here is a taste:

. . . .Doctors currently use drugs to try to get patients' LDL down to a specific target--for most people the target is 120 milligrams per deciliter. But Yale cardiologist Harlan Krumholz and University of Michigan internist Rodney Hayward say this is unnecessarily complicated. Instead, they recommend doctors estimate people's total cardiovascular risk using a multiple risk factors like high blood pressure and age. People with a 15% or higher 10-year risk of suffering a heart attack should get a healthy dose of Lipitor (40 mg); everyone else should take generic simvastin, also at a 40 mg dose. Krumholz and Hayward calculate this method would prevent more heart attacks than bothering with numerical targets, while allowing patients to take lower doses of drugs. . . .

The bottom line: Cardiologists don't know [nearly] as much as you might think about high cholesterol. But they do know that you should watch your diet and exercise. If you are still at risk of a heart attack, consider taking a statin drug like Lipitor or generic Zocor. . . .

Just look at that conclusion -- I think it is an accurate depiction of where most medical professionsals now land, on the Vytorin/Zetia question: it has been effectively answered, at least until 2014 or so (when IMPROVE-IT might be completed, and then published) -- and there is no first, second or third line spot for the drug. There is much more in the article -- including analysis of the Arbiter-6 HALTS termination, among other matters.

4 comments:

Pharma Conduct Guy said...

2010/02/04 at 7:12am [at the backup site]:

Hi Condor,

For years I’ve advocated looking for more clinically relevant endpoints with a particular therapeutic intervention. Although high cholesterol has been linked with heart disease for many years, as Matt’s article correctly states, we still do not really understand the relationship between cholesterol and heart disease.

Cholesterol is one of those interesting biomarkers that falls into the category of a “surrogate marker.” Markers are given this designation when we observe a relationship between their levels and particular disease indication, but we don’t fully or conclusively understand the marker’s relationship to a disease outcome. Does cholesterol cause heart disease, or is it merely a by product of a disease process?

In the end, I do not really care what my cholesterol numbers are; I care about my propensity to have an adverse cardiovascular outcome. The FDA requires drug makers to demonstrate both safety and efficacy, and when deciding whether to approve a drug, they are also supposed to factor in risk and benefit.

When drugs are used to modulate a surrogate marker as part of a preventive strategy, the FDA should do more to require that the probability of an adverse outcome really is reduced. In other words, lowering cholesterol is not good enough. We should know whether or not a particular intervention lowers my risk of a heart attack without increasing my risk for other ailments.

Namaste

Condor said...

From your keyboard — to the pen of Congress. And the pen of our 44th President.

Great comment!

Indeed, Namaste, man.

Eric Milgram, Ph.D. said...

Thanks for the feedback and transferring the comment. I didn't know if I should post here or on the new site, which, by the way, renders outstandingly well on my Droid phone.

Did you optimize it for mobile devices, or is that a WordPress feature? It looks really nice on my phone's browser.

Also, do you have a way that I could contact you directly, such as via email, Twitter, or Facebook? You can reach me at eric(at)pharmaconduct.org or http://twitter.com/EricMilgram.

Condor said...

I assure you it is a Wordpress template (or a Droid pre- render of the Wordpress template) that does all the magic.

I am clearly not coding it. In fact, the feed gets this janky full-justified text look on the iPhone. Go figure -- but only the Wordpress feed.

I'll write you shortly, at yours. On a train at the moment.

Namaste