JUPITER--A Big Deal or Just Lots of Hot Air?

That's my idea of being clever. Perhaps we should just move on...

One thing you can't fault clinical researchers on is a tin ear. They've come up with some doozies for names of various clinical trials, having jiggered the acronyms just so: ACME (Angioplasty Compared to MEdicine), AVERT (Atorvastatin Versus Revascularization Treatment), COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation), and MAGIC (MAGnesium In Coronary Arteries) are but a few of the cleverly-named studies dotting the pages of medical journals. The latest big statin trial (the Covergirl of the November 20, 2008 New England Journal) places itself in this proud tradition, calling itself JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin). That rumbling you hear from Austria is nothing more than Mozart screaming from his grave, don't mind it at all.

Now, statins are very, very interesting drugs, among a small group that Doctor Rubin genuinely considers worthy of the title "wonder drug" (aside from aspirin--the ultimate wonder drug--he would include opiate narcotics, penicillins, antihistamines, and that's about it), and in this respect the JUPITER trial doesn't make any waves. For the non-specialists, statins are drugs that block one of the early steps of cholesterol production, and in trial after trial they have proven their worthiness in reducing the risk of dying from heart disease. They're not completely safe drugs, but they are mostly safe, so as long as you have an MD who's paying attention to your liver (for instance) they have a big impact on people who are at risk for serious cardiac problems.

Here's the thing: it's not fully clear why statins work. Oh, there's the cholesterol-lowering theory, which may well be right. But statins have other weird effects that don't appear to be directly related to what we know about cholesterol "pathways"; they seem to have anti-inflammatory effects and affect bone resorption. JUPITER's strategy, which seems to me to be fairly novel although I am not a specialist in this field, was to enroll people who had normal cholesterol levels but did have elevations in a chemical marker of inflammation called C-reactive protein, or just CRP. The trial, originally scheduled to last for 4 years, was stopped after about two because of the significant reductions in cardiovascular events (such as heart attacks). There is some dispute as to the magnitude of this benefit (as seen in an accompanying editorial here, see fourth paragraph about differences in relative vs. absolute risk), but it is hard not to find the data impressive.

My question--and the question of this entry--is: regardless of the success of the JUPITER trial and whether or not it has identified other groups of people who may benefit from statins, has JUPITER also popped the bubble on the idea that cholesterol is the key metabolic player in the drama that causes the MI? Perhaps cholesterol is really a surrogate marker and has only been the center of our focus because it's one thing that we could, in fact, focus on? We will see if the basic physiology labs have any thoughts on whether or not we have been searching for our lost car keys under the lamp-post because that's where we had some light.
--br