JUPITER is a Joke.

For those of you scratching your heads and saying, “What the heck is JUPITER?”, JUPITER is the latest study purporting to show cardiovascular benefit from taking statins.  In other words – take a statin, prevent a heart attack.  After the disastrous results of the ENHANCE study, statin supporters really needed a win – and they apparently got one in JUPITER (or did they?  Skip to the last paragraph in this post for the punchline; otherwise, read on).

(For the interested – my favorite article on the JUPITER study, and the actual study itself.)

Some necessary science:

If you’re a regular reader of my blog, you’ll know that I’m no fan of statins.  Why?  Because they are used to lower cholesterol levels in an effort to reduce incidence of heart disease.  What’s so bad about that, you ask?  First, there’s really no compelling evidence to suggest that cholesterol levels are tied to heart disease, so trying to thwart heart disease by reducing cholesterol – specious at best.  Second, there’s ample evidence (and plenty of reports) that statins cause nasty side effects – liver damage and muscle wasting, to name two outstanding ones.

A drug that doesn’t do what it purports to do, while injuring the patient who’s taking it?  Sounds iffy to me.

It’s undeniable that statins do decrease cholesterol levels, and that they’ve been to shown to have a (slight) protective effect in males over the age of 65 who’ve had a previous cardiac event (and no beneficial effect to all other groups).  But what’s been disputed is just how they deliver that benefit.  After all, if lowering cholesterol doesn’t protect against heart disease, then what’s providing the protective effect?

Answer: Decreased inflammation.

Chris Masterjohn’s awesome chart shows that increased inflammation causes levels of cholesterol to rise, and that statins decrease cholesterol production indirectly by inhibiting HMG CoA reductase (and consequently, decreasing mevalonate production – a precursor for cholesterol synthesis).  Note that by affecting the pathway so high up, statins have other effects as well (decreased Rho activation, for one).

In simple English – statins don’t work by walking up to rogue LDL particles and hacking them into tiny pieces, they prevent the body from making them altogether by cutting off the supply of raw materials.  And cutting off these raw materials makes it so that the body can’t manufacture other compounds, either; some that lead to harmful outcomes (i.e., inflammation).

C-reactive protein is a marker for inflammation; the more CRP you have, the more inflammation you have.  And as you can guess, that isn’t a good thing for longevity.  Well, it turns out that because subjects in the study had low LDL and total cholesterol levels but high CRP levels, the JUPITER study may force doctors to reevaluate the validity of the lipid hypothesis (that cholesterol causes heart disease).

I guess you could say that’s the one good thing to come out of the JUPITER study.

Ok, so enough dancing around it – the punchline:

The study was originally meant to track all patients for five years, but the results were so robust that it was terminated after a median follow-up of 1.9 years. In March an independent panel of observers halted it because they considered the effects of the drug to be so beneficial that it would have been unethical to keep the control group on a placebo (emphasis mine).

Oh really?  Is that the reason why?  Or could it be because of this (quoted from the actual study):

The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes (emphasis mine).

Did the independent panel really halt the trial because they were oh-so concerned for the well-being of the placebo group?  Or was it because they were worried that the wonderful results of the Crestor group would be slightly marred if they developed diabetes?

Or could it be that they halted the trial because they got what they wanted (great results for the statin group) and wanted to stop before any of the long-term problems that plagued participants of prior studies (like cancer and stroke in the ENHANCE and SEAS studies) had a chance to develop?  In his insightful post on this topic, Dr. Eades mentions that:

…it is typical for an outside group to take a peek at the data at certain milestones to make sure the study medication isn’t killing people…I’ve never seen a study halted because the placebo group was dying at higher rates. That really makes me wonder.

I don’t doubt that there was foul play afoot.  After all,

…physician-reported diabetes was more frequent in the rosuvastatin group; these events were not adjudicated by the end-point committee.

“We didn’t study it so it didn’t happen”, or something like that.  Sounds like they got out while the gettin’ was good.

UPDATE #1: Peter shows us why it’s so important to look at the actual data.  Deaths from cardiovascular disease in the statin group were higher than the controls (the controls had more incidence of CV disease, but fewer deaths).

UPDATE #2: Sandy’s review of JUPITER is ridiculously awesome.  Set aside an hour and read it.