ARBITER 6 - HALTS - my 2 cents

Shifting gears from running to lipids for a few minutes, I want to throw my 2 cents in about the ARBITER 6 trial that appears to be one of the most anticipated studies revealed at AHA this year. It's a trial that compared the ultrasoncially measured carotid intima media thickness (CIMT) of patients taking a statin with niacin and a statin with zetia (ezetimibe) over time. CIMT is considered to be a surrogate marker for coronary artery disease, which is considered to be a surrogate marker for cardiovascular injury or death. In other words, it's comparing the thicknesses of plaques in artery walls in the neck of groups of patients on two different groups of medicines, with the speculation that the greater decrease in the size of that plaque (or the lesser increase in size) will translate into fewer heart attacks, less heart disease, fewer deaths, etc.
It's interesting to me that a trial based on surrogate endpoints and that deals with two risk factors that both have an effect on cardiovascular health is garnering so much attention. There has been much speculation that the trial was stopped early because the niacin arm proved to be superior to the ezetimibe arm- if so does this come as any big surprise? From what I can tell, there is no mechanistic reason for zetia not to work, but when used in combination with a statin, it will only cause a added 15 to 20% decrease in LDL-C and will have minimal effects on other parameters. In contrast, niacin will potentially decrease LDL by about 10%, but will also raise HDL substantially. It also has an effect on HDL and LDL particle number as well as triglycerides. I don't think that it would be too surprising if it turned out that manipulation of these multiple parameters (all of which seem to have a positive effect when it comes to coronary artery disease) turn out to be more effective than basically just lowering ldl? Would anybody be surprised to find niacin to be the superior drug with this in mind?
On the other hand, I do not think that a negative result for ezetimibe in this trial would necessarily be a "death nail" for that drug either. First, this study is an imaging study, not an outcome trial, so results have to be taken with a grain of salt - we'll have to await Improve It in 2012 for mortality data with ezetimibe (a negative or equivocal trial in that situation may be a signal to start the funeral dirge). Second, ezetimibe seems to be a relatively safe drug, so, I don't see any good reason not to use it in combination with niacin and/or a statin. Third, though niacin appears to be the perfect complementary drug to a statin, unfortunately in clinical practice, its side effect profile does seem to be a limiting factor in its use - if zetia works, but not as well as niacin, it still may be a viable alternative to niaspan in those who can't tolerate the later.
I'll also be interested to see what the mean LDLs are for each group - if the entire group is at or near goal (because of their baseline statin use), then perhaps lowering the ldl further (with zetia) is not nearly as effective as manipulating other cardiovascular risk factors (niacin).
In short, I use a lot of use a lot of niacin in practice - and pretty much regardless of the results of this trial, I still will. I use zetia largely as an adjunct to statin therapy in LDL lowering in patients who are on a maximally tolerated dose of a statin, but who are not at goal (or with those who seem to have "statin tachyphylaxis"). I never liked the idea of using zetia as a substitute for a higher dose of a statin if the individual could tolerate the statin, and I still don't . I have always thought that niacin was underutilized, and this trial may lend some credence to this this idea, but otherwise, unless there is a truely surprising outcome, I'm not sure how much it will alter my practice patterns.