Friday, November 29, 2013

The Cholesterol Conundrum

Originally published in The Vault Magazine, November 22, 2013.

On November 12, the American College of Cardiology and the American Heart Association released an update to their clinical guidelines for the management of high cholesterol.  Amid all the ensuing controversy and debate, the most remarkable facet of the guidelines was forgotten.

Previous guidelines promoted measurement of cholesterol and frequent monitoring for the purposes of “getting to target”.  Start treatment, measure cholesterol, adjust treatment if it needs to go lower, and repeat.  

The new guidelines suggest these numbers be almost entirely abandoned in clinical practice.  If a patient has excessive heart disease risk and it has not been ameliorated by lifestyle changes, they suggest you take a statin (eg. LipitorTM and CrestorTM) and be done with it.  The cholesterol measurement only remains important for determining risk. 

It’s about time.  These targets were always arbitrary.  They have no scientific underpinning and led to excessive treatment including unnecessarily high doses and use of drugs that have no proven benefits beyond lowering cholesterol.  

Wait a minute.  If a drug lowers cholesterol, isn’t that good for you?  

Not exactly.  And herein lies the public interest in this issue.  

Cholesterol is a “surrogate marker”.  If studies show lower cholesterol correlates with lower heart disease risk, then a drug developer might look at the impact of their treatment on cholesterol and assume any reductions in this number translate into reductions in heart disease.  Measuring heart attacks, strokes, and deaths in your research takes time and money.  Measuring cholesterol does not.

If A=B and B=C, in medicine at least, A does not always equal C.  

For example, many cholesterol drugs on the market reduce bad cholesterol but only statins are known to reduce heart disease.  

Not convinced?

Torcetrapib was a drug being developed by Pfizer which showed great promise as the next “blockbuster drug”.  Early small studies showed the drug raised good cholesterol by 60-100%.  This should, by extension, mean it reduces heart disease.

Shortly after, Pfizer’s large clinical trials were stopped early because the drug increased risk of death by 60%.  

Why should you care?  

Because the media, TV doctors, and internet snake oil marketers LOVE surrogate markers.

Dr. Oz’s most popular recommendation of the year has undoubtedly been raspberry ketones for weight loss.

Too bad they’re useless.

His website quotes all sorts of research on the topic to lend it credibility but it is useless for everything but hypothesis generation.  All the studies he quotes were done on animals or in test tubes and they studied things like markers of metabolic rate and fat metabolism.  

Not a SINGLE piece of research shows raspberry ketones do ANYTHING useful in humans, let alone cause them to lose body weight or body fat.  

THAT is why you need to know about surrogate markers and why from now on, you will know to ignore practically everything Dr. Oz says.  

Unless by some miracle he starts promoting products based on high quality medical research conducted on humans.

I can dream.

Next time: Why some would argue that ice cream causes swimming pool drownings.

Other Resources
A hilarious video on surrogate markers from my friend and colleague, James McCormack, PharmD.


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