Tuesday, July 03, 2007

Cholesterol ratios through the looking glass

It is a foundation stone of modern cardiology that cholesterol causes heart disease. The roll of LDL-cholesterol is central. This is "bad" cholesterol. The cholesterol of the Dark Side. Then there is HDL-cholesterol, the "good" cholesterol. Feel the Force Luke.

You know the theory, people eat lots of fat and eggs, make lots of LDL-C. This sticks to the artery walls, bungs them up and a heart attack happens. You've seen all the ads on TV for cholesterol lowering by this or that health food.

But until the statin drugs arrived on the scene this theory was pretty well moribund. Every method of lowering cholesterol ever developed, from diet through cholestyramine to fibrates, had a nasty habit of leaving total mortality unchanged. In some studies it even went up, and almost always in unpleasant ways.

Not so with the statins. The big plus side for statins is that they save lives. Ok, only if you have already had a heart attack first. And not many lives, but some. Being a bloke helps them work too, rather a lot. They do this, we are told, by decreasing bad cholesterol levels, particularly LDL-C, while increasing HDL-C, the good one. Yawn.

Now just imagine a "super drug" which could be added to the weakling statins to produce such a fantastic fall in LDL-C combined with such a rise in HDL-C that it is now possible to actually have an HDL-C level HIGHER than your LDL-C level. By quite a lot! This no minor feat. How good was the outcome? In this drug induced cardiological Nirvana, heart attacks must be banned for ever. Surely they must be. Please.

Except they're not.

The drug is (oops I mean was) torcetrapib and it's been pulled from development by Pfizer because adding it to atrovastatin doubles the cardiovascular catastrophe rate.

These two studies (RADIANCE 1 and RADIANCE 2) were published side by side in NEJM, to which I don't have access. Fortunately the nice people at the HDLforum.org do.

They give the cardiovascular catastrophe rate for torcetrapib combined with atrovastatin as 5.2% vs. 2.4% for atrovastatin alone from the RADIANCE 1 study. The same values from the RADIANCE 2 study are 9.5% vs. 5.6% respectively. These values are not in the abstracts for pretty obvious reasons!

So where does this leave torcetrapib? It appears to be in the rubbish bin, where it belongs! What about the good vs bad cholesterol hypothesis? This goes on as before, despite the increased heart attack rate in the subjects with deliriously high HDL-C and almost no LDL-C . I believe the usual phrase is something like "We wus unlucky, Guv" accompanied by head scratching.

Lowering LDL-C while raising HDL-C has been the Holy Grail of cardiology for some time. Now it's been done, with a vengeance, and it sucks.

The statins are the only lipid lowering drugs to decrease overall mortality in heart attack patients. Not by much, and you have to have had a heart attack first. They only work because they're anti thrombotic, anti inflammatory, anti proliferative, anti oxidant and anti a few other things too. Isn't the toxin (lovastatin) from a mould which grows on rice clever. Especially when compared to Big Pharma's torcetrapib! The cholesterol lowering aspect of lovastatin is an unpleasant and unnecessary side effect. Like the coenzyme Q10 depletion.

Your cholesterol ratios are useless. Thank you Pfizer for torcetrapib. RIP the lipid hypothesis. Again.


PS torcetrapib was doomed from the start because it had no X Y Z or V in its name. Blame the marketing folks.

1 comment:

HeartCipher said...

Great post Peter...

Insightful and hilarious.