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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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September 22, 2009

Statin Safety?

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Posted by Derek

Senator Charles Grassley of Iowa has sent the FDA a letter asking if the agency has sufficiently considered adverse events from statin drugs. I've been unable to find the text of the letter, but here's a summary at Business Week. (Grassley's own list of press releases, like most other senators and representatives, is a long, long list of all the swag and booty that he's been able to cart back to his constituents.

His main questions seem to be: has the agency seen any patterns in adverse event reports? Is there reason to believe that such events are being under-reported? Is there information from other countries where the drugs are prescribed that might tell us things that we're missing here?

Business Week's reporter John Carey has been on this are-statins-worse-than-they-appear beat for some time now, and it wouldn't surprise me if someone from Grassley's office sent him a copy of the Senator's letter on that basis. Those considerations aside, are statins really worse than they appear, or not?

The muscle side effects of the drugs (rhabdomyolysis) have been known for some time, and it's clear that some patients are more sensitive to this than others. But there are other possible side effects kicking around, such as cognitive impairment. The evidence for that doesn't seem very strong to me, at first glance, and could (as far as I can see) come out the other way just as easily. In the same way, I haven't seen any compelling evidence for increased risk of cancer, although it's quite possible that they may have effects (good and bad) when combined with existing therapies.

The one thing that you can say is that the epidemiological data we have for statin treatment is probably about as good as we're going to get for anything. These drugs are so widely prescribed, and have now been on the market for so many years, that the amount of data collected on them is huge. If that data set is inadequate, then so are all the others. I'm not sure what Sen. Grassley is up to with his letter, but that's something he should probably keep in mind. . .

Comments (20) + TrackBacks (0) | Category: Cardiovascular Disease | Regulatory Affairs | Toxicology


COMMENTS

1. barry on September 22, 2009 11:45 AM writes...

The safety of current statins rests on impressive datasets including millions of users. These however are the winners among a larger set of statins that got approved by the FDA before the subtleties of tissue distribution were appreciated. In retrospect, a statin that spends more of its residence time in the liver has fewer side effects in the muscles. Alas, that was learned only after the commercial launches of Lipitor (a winner) and Baychol (a loser)

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2. Slothy on September 22, 2009 11:56 AM writes...

Not only is the risk of Alzheimer's and dementia lower in statin users, statins may be a potential treatment for traumatic brain injury and cerebral ischemia. They seem to reduce inflammation and induce neurogenesis.

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3. anchor on September 22, 2009 1:09 PM writes...

Is Sen. Chuck Grassley of Iowa taking any of statin medication? Hmm..just curious. One of his congressional aid ought to tell him the good outweighs the bad, when it comes to statins. Statins are one of the most intensely investigated in clinical trials. The ground is solid here.

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4. Paul on September 22, 2009 3:55 PM writes...

Statins inhibit ubiquinone synthesis, don't they? I wonder if there are side effects related to this.

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5. metaphysician on September 22, 2009 4:03 PM writes...

Am I the only one whose first thought was "Gee, Senator, wouldn't it suck if you set off a panic about statins causing cancer/neurological decay/ingrown toenails, people went off the drug en mass, and thousands more people died of heart disease than any conceivable side effect could have ever killed?"

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6. RTW on September 22, 2009 4:06 PM writes...

I think I posted on this subject before. We have known for a long time that Statins seemed to exert some anti-imflamatory response in the cardio vascular system. As for 1) Barry - Your observation was the basis of research done in Ann Arbor, years later as a follow up to Lipitor, to further improve this as a differentiation. We had some interesting candidates, but I don't beleive Pfizer ever chose to take any of them into the clinic. Papers have been published on them. But I don't know any thing more. In fact Derek I beleive you may now work with one of the PI's.

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7. Old Pharma Guy on September 22, 2009 8:46 PM writes...

It's likely that the muscle-related side effect are due to mitochondrial toxicity. Jin Dykens at Pfizer published some pretty convincing work on tis area. This may be hard to sort out by conventional genomics if the genes responsible for sensitivity are in the mito's genome.

What I'd love to see is the relative risk of taking statins vs the benefits derived. Otherwise, these reports lack context.

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8. Old Pharma Guy on September 22, 2009 8:46 PM writes...

It's likely that the muscle-related side effect are due to mitochondrial toxicity. Jin Dykens at Pfizer published some pretty convincing work on tis area. This may be hard to sort out by conventional genomics if the genes responsible for sensitivity are in the mito's genome.

What I'd love to see is the relative risk of taking statins vs the benefits derived. Otherwise, these reports lack context.

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9. New PharmaGuy on September 23, 2009 1:03 AM writes...

Am I the only one noticing the irony of a Republican Senator from the Midwest castigating one of the most researched and profitable drugs in the past half-century (epidemiology and randomized trials) which provided the funds which the industry in turn donated to the Republican Party for much of that half-century. Talk about biting the hand that feeds you!

Perhaps it's time for PhRMA to arrange for Senator Grassley to have a Mini-Mental Status Exam?

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10. Morten G on September 23, 2009 4:02 AM writes...

Didn't anyone read the 5-6 page article in Nature about Paul Thacker, Grassley's investigator who did the whole "academics who do not disclose their conflicts of interest properly" thing? It's pretty much Grassley's shtick to be a pharma watchdog. Which someone has to be, I'd like to point out.

The reason you couldn't find a press release Derek is that there wasn't one: "BusinessWeek has learned that Senator Chuck Grassley...". Which means that Thacker called them up and said "Hey, guess what". Politics. And the reason they are asking the FDA about statins is that there are so many people taking them -> so many votes in it.

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11. anyone on September 23, 2009 8:59 AM writes...

1)Barry, 6)RTW, - can you guys provide a reference or two? I'd like to check out the tissue distribution thing.

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12. RTW on September 23, 2009 9:51 AM writes...

11. anyone. Sorry - I no longer have access to such literature resources as I once did. This is from memory when I use to work for the goose that laid the golden egg for 20 years. I have been away for 3 years now. About 5 years ago I worked on a follow up to Lipitor. It was a very large effort. There may be some papers on the subject from the following medchem authors: G Bolton, J Dunbar, R Hutchings, R Kennedy, D Leonard, t Mertz, W Park, J Pfefferkorn. The only presentation I was a co-author of was at an internal symposium.

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13. JE on September 23, 2009 12:37 PM writes...

One recent review cites nearly 900 studies on the adverse effects of statins:

"Muscle problems are the best known of statin drugs adverse side effects, said co-author Beatrice Golomb. But cognitive problems and peripheral neuropathy, or pain or numbness in the extremities like fingers and toes, are also widely reported."

Byron Richards gives a plausible explanation of how statins could have caused Senator Edward Kennedy's brain cancer.

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14. David on September 23, 2009 6:29 PM writes...

Excuse me, J, but that's plausible? Statins have been well examined epidemiologically upwards and downwards for a cancer risk, and in a phrase, nothing's been found. So this is a plausible explanation? Machination might be a better description.

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15. Fries with That? on September 24, 2009 1:20 PM writes...

Derek,
I no longer doubt how bad statins can be, my brother developed muscle aches and pains after taking them, which still come and go and bother him more than a year after he stopped. Of course, when he complained to his physician, she referred him to a therapist and upped his statin dose. Only when he decided to quit taking them did he feel better.
Our father could not tolerate them either, and I have a friend who also had severe muscle ache associated with statins. Anectodal? Perhaps, but my family lacks the billion dollar budget to follow up.
Also, I wonder if some type of whole body neuropathic pain is involved in this side effect, since it waxes and wanes.

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16. Med Chemie on September 24, 2009 4:41 PM writes...

Fries:
What whiny crackpots! Statins have proven time and time again to be the safest drugs out there with very minor side-effects, if any. And they have saved MILIIONS of lives. To convince people otherwise would be tantamount to first-degree murder.

I bet your family members also believe in colloidal silver, "positive energy" machines and homeopathy as well.

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17. Anonymous on September 25, 2009 2:03 PM writes...

Med Chemie,
Does the phrase "personalized medicine" ring any bells with you, or did you completely skip biology courses?
No, we don't believe in the nonsense you describe in your last paragraph, however, we do believe that some people out of the millions will experience adverse effects, and they happen to be in my family.
BTW, insulting one's family is poor manners, poor taste and poor class.
I'm just curious, how long have you been a CEO?
cheers,
Fries

Permalink to Comment

18. John Carey on September 29, 2009 1:03 PM writes...

Hi Derek,
Thanks for mentioning my story about the Grassley letter. Just respond to some of the speculation, the answer is 'no.' No one from Grassley's office called me up or sent me the letter (which was not publically released), so those seeing a political motive will be disappointed.
As for statins themselves, I would also refer people to a longer story I did that looks more in depth at the data on efficacy (but with more on side-effects as well). http://www.businessweek.com/magazine/content/08_04/b4068052092994.htm

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19. fetz the chemist on October 4, 2009 10:20 PM writes...

I am one of those millions that the pharma companies call the rare people with the muscle damage side effect. It would have been much less noticable if I had not had a severe strained calf muscle a year before I started taking them and a strained muscle in my left shoulder blade area two years before. The attacks are not too acute, a low, dull ache in regular muscles, but those recently injured and probably only partly healed ones were very intense and localized to those spots. I wonder how many people without such injuries just ignore the slight aches as a side effect of older age.

My doctor freely prescribes statins, and I've heard he often goes to the pharma boondoggle seminars in Hawaii and other resort areas.

I switched to niacin. The flush and feeling heated with it happen once in a while, but my cholesterol level is as low as with the statins. But the niacin also costs less than a tenth as much.....there's the rub. Yjr pharma companies have freely funded any research using statins in hopes of getting a correlation to a good effect. The researchers rarely report the support and you get more reasons to prescribe more billions of dollars.

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20. marjorie on October 30, 2010 3:40 PM writes...

Common wisdom leads us to believe that statin drugs save millions of lives. Is there actual science behind this? Where is the study? One thing is certain, they bring in billions of dollars in sales for big pharma.

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