Wednesday, November 18, 2009

David Rind, M.D., Internist -- Beth Israel Deaconess Medical Center (Boston) -- Launches A Very-Promising Blog

[Earlier today, I ran some content derived from his nascent blog -- and it looks to be a good one. Do go take a look at all he's offering, but this is a reprint, as it kinda' got buried in a flurry of rather-silly posts I tossed up, this afternoon. . . .]

On the "Fragility" of the Arbiter 6 - HALTS Cardiovascular Events-Data

Thanks to reader Marilyn Mann -- for this link to an article in Evidence in Medicine:

. . . .Now, soon after that study, we have ARBITER 6, showing that niacin plus a statin seemingly reduced cardiovascular events compared with ezetimibe plus a statin. There were 2 events in the niacin arm (1%) and 9 in the ezetimibe arm (5%) and this was statistically significant. So, what can we conclude from this?

One possibility is that niacin actually does add some clinical benefit to a statin in secondary prevention, while ezetimibe does not.

Another possibility is that ezetimibe is actively harmful, while niacin is neutral. There were slightly more events in ENHANCE in the ezetimibe arm, but the numbers were tiny.

A third possibility is that this was due to chance. The actual results are quite "fragile" in the sense that only a few events moving from one arm to the other would make the difference disappear. While, in theory, a statistical test captures this, there's been a sense in the EBM world that very small event numbers create a fragility of results not adequately captured by a p value. It seems extremely unlikely that niacin really reduces events by 80%, since this should have been obvious in prior trials of niacin. As such, either niacin combined with a statin is much superior to niacin alone, or these results are in part due to the play of chance. (It's not likely that ezetimibe raises events by this degree when used with a statin, since we would likely have noticed this in other trials.). . . .

Interesting. Do go read it all. Back later with more, but here is Marilyn's take:
. . . .A fourth possibility is that niacin adds a small cardiovascular benefit and ezetimibe adds a small cardiovascular harm.

Question: you seem to be saying that ARBITER was a secondary prevention trial. Yet some of the patients did not have known vascular disease. The trial included patients with a calcium score over 200 for women or 400 for men or Framingham risk scores over 20%. (There were also patients with diabetes who did not have known vascular disease, although diabetes is usually classified as a coronary risk equivalent.) Admittedly the primary prevention patients were *very* high risk. Still, if someone is totally asymptomatic but either has multiple risk factors giving them a high FRS or known extensive atherosclerosis as indicated by a high calcium score, isn't that still primary prevention?

In my view, the issue of whether ezetimibe promotes cancer and/or cancer death is still unresolved, although I know you are a skeptic on that issue. This trial does not tell us anything about that.

Posted by: Marilyn Mann | Nov 18, 2009 at 09:37 AM


Eric Milgram, Ph.D. said...

This is a great post. I've asked an expert statistician to weigh in on it.

Anonymous said...

speaking of stats - go check out comments on the "Courtesy Marilyn Mann -- On The "Fragility" of Arbiter 6 Cardiovascular Event Data" and Matt Herper's piece posts below.

Anonymous said...

Oops - make that speaking of stats - go check out comments on the "Insurer-sponsored post hoc 30,000 patient study" and Matt Herper's piece posts below.