Wednesday, November 18, 2009

Insurer-Sponsored Post Hoc 30,000 Patient Study: "Merck's Vytorin Of No Incremental Benefit"

Yes, the sponsor of the study has a financial incentive to see patients take less pricey medicines (especially if the results don't really differ, between outcomes from the pricey and the cheap drugs), and yes it was not peer-reviewed, or vetted, as a NEJM article would be, but it did examine 30,000 patients' histories. That makes it twice the size of the much debated IMPROVE-IT trial, still stuck at 15,000 patients.

Peter Loftus, for the Wall Street Journal, reporting from the AHA, in Orlando:

. . . .A new study by health insurer UnitedHealth Group Inc. concludes Merck & Co.'s cholesterol drug Vytorin didn't significantly reduce the risk of heart attacks or strokes compared with a generic alternative or Pfizer Inc.'s Lipitor. . . .

"Treatment with the combination Vytorin drug really showed no significant difference in those clinical results when compared with what we tried to match up as equipotent doses of simvastatin and [Lipitor] alone," said Brian Solow, senior medical director at Prescription Solutions. . . .

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. . . .The analysis suggests that heart patients may fare just as well by taking the least-expensive cholesterol-lowering pill. Simvastatin costs 84 cents for a 40 milligram dose, compared with $3.91 for the same dosage of Lipitor and $3.74 for Vytorin. A study last year showed that Vytorin worked no better than simvastatin at reopening arteries and a separate study reported this week found that Abbott Laboratories’ Niaspan may be superior to Vytorin in certain patients. . . .

"This looks at a real world context of 30,000 total lives and we are looking at the lives they would normally lead while on these medications," said Brad Curtis, a vice president and medical director for Prescription Solutions. "We are showing how it looks out there in the real world. . . ."

The evidence continues to pile up, here.


Anonymous said...

Let's do a little number-needed-to-treat (NNT) and economic analysis, shall we?

From the Stockl presentation of these data at AHA:

Simva/ezetimibe 96 events/9983 pts over 1.06 yrs of f/u = 0.91%/yr event rate

Atorva 115 events/9983 pts over 1.16 yrs of f/u = 0.99%/yr event rate

Simva 124 events/9983 pts over 1.08 yrs of f/u = 1.15%/yr event rate

NNT = 1/absolute risk difference

Simva/ezetimibe vs atorva NNT = 1250. This means you'd have to treat 1250 pts to prevent one event with simva/ezetimibe vs atorva.

Simva/ezetimibe bs simva NNT =417

Assuming simva costs 84 cents/d, atorva $3.91/d, and simva/ezetimibe $3.74/d:

You'd have to spend $1.7 million to treat 1250 patients for one year with simva/ezetimibe vs atorva to prevent 1 event, or spend $570 million for simva/ezetimibe vs simva for one to prevent one event.

Since your average stroke/MI hospitalization costs about $30,000, we would have to spend way too much money to use simva/ezetimibe vs either atorva or dirt-cheap generic simva. I'm no Peter Orszag, but I'm pretty sure there's no way that will ever be viewed as cost-effective.

Don't think we'll be seeign any such analysis out of the Merck health outcomes shop any time soon.

Eric Milgram, Ph.D. said...

I have a copy of the actual paper and supplementary material from the NEJM. After a very cursory glance, I'm leaning toward's the following explanation from Mann:

"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.). . . ."

I probably won't be able to give this a thorough review until the weekend, at the earliest, but I'm going to contact Taylor to see if I can get 1) the raw data and 2) an explanation of the total number of statistical tests actually performed. I didn't see any mention of correction for multiple testing. However, if the tests in the paper represent the bulk of what the tests they actually performed, then I understand why they wouldn't have a multiplicity correction.

Ignoring the question of safety (yes, I know we shouldn't do that), but many are starting to the right question: if you have to look this hard to find a benefit to Simva/ezemtimibe over niacin, how can you justify the cost?

By the way, I know from personal experience that the flushing from niacin is very uncomfortable. Although I don't need cholesterol lowering agents, I took some niacin just to see if the flushing was as bad as some people report. For me, it was. However, if I had to be on a cholesterol lowering agent and was paying for it myself, I would learn to live with the flushing. Several people have told me that the intensity of the flushing diminishes after 1-2 weeks of regular use.