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Friday, December 18, 2009

Will CRP(c-reactive protein) become a cocktail dinner conversation?

The answer to the title question is "probably yes" if the FDA concurs with the recent recommendation of its advisory committee in regard to a "new" indication for rosuvastatin (Crestor).

Dr. Matthew Mintz gives his thoughtful analysis of the panel's decision ( see here) and,in general, he seems to support the decision of the panel. The panel basically approved rosuvastatin for patients with normal LDLs and an elevated hs-CRP (high sensitivity CRP).

As has been pointed out (see here for Sandy Szwarc's detailed comments and critique on the study (Jupiter) that lead to the panel's decision) a very large number of people would be "eligible" for this new indication.I believe her comments contain several important counter-points to the avalanche of glowing comments from well known "thought leaders" that came quickly on the heels of the publication of Jupiter in the NEJM and should be read by someone before planning to check everyone's CRP and treat those eligible folks with CRPs of over 2.Although, I'll bet that the media blitz and specialty society guideline publicity that will blare forth if and when the FDA gives final approval will overwhelm any suggestion by a physician that we might give the matter a little thought before we prescribe Crestor because of an elevated CRP.

A 2009 article by Dr. Erica Spatz concluded " JUPITER’s findings have the potential to impact treatment recommendations for 20% of middle-aged to elderly adults, thus increasing the proportion of this segment of the population with an indication for statin therapy to nearly 80%."

That 80% of middle-aged and elderly should be on a statin is ,to put it mildly, mind boggling.

One comment by a FDA panel member caught my eye-that the increases of new onset diabetes in the Jupiter trial was a "class effect" meaning that all statins tend to do that. For the number of patients for whom I recommended statins I did not see fit to warn them about an increased risk of diabetes. I was not aware of any. In fact, the West of Scotland study (WOSCOPS) found a 30% reduction in the onset of new diabetes in the pravastatin treatment arm. JUPITER had reported the opposite namely that there were 3% new diabetes cases in the treatment arm versus 2.4% in the placebo group. Further, Rajpathak published a meta-analysis of six statin trials that demonstrated a slight increase if the WOSCOPS data were excluded but no difference in onset of diabetes when that data were included. ( I never did understand why they would want to exclude the Scotland study anyway but...) So, if it is a class effect it must be a rather small one and I would worry more about muscle toxicity related side effects in the newly enlarged pool of older eligible patients.

So much has been written,just in the medical blog world,that I won't try and summarize all of the gleeful announcements of a really big breakthrough or the more somber critiques. But if you read only one commentary this one by DrRich would be worthwhile.

You can talk about the fact that Jupiter was terminated prematurely, you can talk about relative risk versus absolute risk reduction and Crestor effect versus class effect but in the end here is the way things seems to work. When you have a large randomized clinical trial that demonstrates a benefit for a given medication and when many well known medical thought leaders endorse it and when it is then approved by the FDA you know that guidelines will be written and quality rule driven medical practitioners will follow and many patients will take the medication and likely insurance companies will pay for some or all of it.So in this case many folks will have their hs-crp checked and they will be prescribed Crestor ( a few will be given lower price statin cousins) and there will be- for a while- talk about crp at parties.

My first prediction for the new year: Look for a surge of CME-oid meetings and articles on the value of CRP for cardiac risk assessment and as basis for statin therapy.Yes, we have heard about CRP for quite a while but soon we will probably have the blessing of the FDA and things will really take off.


Anonymous said...

I cannot recall what site I read it on, but I thought something just came out that said CRP was not a predictor of events, and perhaps is just a symptom. I could be wrong.

Michael Kirsch, M.D. said...

CRP is a surrogate, an event which can take on a life of its own. Cardiologists went gaga over the CRP and the statin manufacturers were salivating. It's quite a leap to connect the dots between an elevated CRP and an impending cardiac event. Yet, the therapeutic locomotive steadily moves forward. www.MDWhistleblower.blogspot.com