November 19, 2010 | 1:19 pm

Apathy about Anacetrapib

Posted by Albert Fuchs, M.D.

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The new cholesterol medication generating hubbub this week is anacetrapib.

Why is the world holding its breath for another cholesterol medicine in an already crowded field?  Well, the most successful family of cholesterol medications is statins.  Statins have solid evidence for stroke and heart attack prevention.  Statins lower LDL, the “bad cholesterol” that you hear about whenever your doctor discusses your cholesterol results.  But another important risk factor for heart disease is low HDL.  HDL is the “good cholesterol” that protects against stroke and heart attack; so more is better.  People with HDLs below 40 are at increased risk for stroke and heart attack.

Thus far, there has not been any medication that substantially increases HDL and prevents stroke and heart attack.  That makes raising HDL an inviting target for pharmaceutical research.  Sure enough, those brainy scientists discovered a new family of medications – CETP inhibitors – which raise HDL.  More HDL should mean fewer heart attacks!  There was much rejoicing.

And this is where we get into trouble if we confuse clinical outcomes with intermediate outcomes.  (See below for a link to my post in 2007 that explains the difference.)  It’s entirely possible for a medication to lower LDL without preventing heart attacks.  (Estrogen is the most notorious example.)  It’s possible for a medicine to increase bone density without preventing fractures.  So it’s entirely possible that a medicine may raise HDL without having the intended clinical benefit – preventing strokes and heart attacks.

In 2007 a large study tested a new CETP inhibitor, torcetrapib, and found that it increased HDL substantially while also increasing heart attacks and death.  There was much grief and woe (especially at the company that makes it).  The important lesson is that fixing the intermediate outcome (low HDL) doesn’t necessarily lead to fixing the clinical outcome (heart attack risk).

This week a trial was published in the New England Journal of Medicine testing a new CETP inhibitor, anacetrapib.  Given the disaster with its older cousin torcetrapib, this trial was just designed to measure safety, not efficacy.  So the trial showed that anacetrapib lowered LDL, raised HDL substantially, and (unlike its cousin) didn’t kill people in large numbers.

That’s nice, but not a reason to pop champagne corks.  Now the large trial begins to show whether it actually prevents strokes and heart attacks.  We won’t have that answer until 2015.

Learn more:

New York Times article:  Merck Drug for Cutting Cholesterol Is Promising

Wall Street Journal Article:  Cholesterol Drug Advances

New England Journal of Medicine article:  Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease

My post in 2007 about the difference between clinical outcomes and intermediate outcomes:  Merck Knows More about Zetia than They’re Telling Us

Tangential miscellany:

This week’s New England Journal of Medicine published a gut-wrenching story of a medical emergency on an airplane.  The handful of doctors on board faced a difficult ethical dilemma.  If you have a few minutes, give it a read.  What would you have done?

And finally, as physicians have done for countless generations, I’m now using Twitter.  I’ll try to tweet an interesting health-related headline daily.  If you’re on Twitter, follow me!

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