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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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« Bias in Industry-Funded Trials in Rheumatoid Arthritis? | Main | What Sanofi Thinks About You »

February 29, 2012

Statin Safety

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Posted by Derek

You'll have seen the news about the FDA safety warning on statins. The agency is warning that instances of hyperglycemia have occurred with statin use, as well as memory loss and confusion.

I'm really not sure what to make of this. On the one hand, these drugs have been through many, many large clinical trials under controlled conditions, and they've been taken by a huge numbers of patients out in the real world. So you might think that if these effects were robust, that they might have been noticed before now. But there are side effects that are below the threshold of even the largest clinical trials, and a patient population the size of the one taking these drugs is just where you might be able to see such things.

I lean towards the latter, and if that's true, then the agency's statement is appropriate. If these could be real effects in some patients, then it's worth keeping an eye out for them. One problem, though, is that hyperglycemia is rather more sturdy. You can measure it, and people don't really feel it when they have it. Memory loss and confusion are fuzzier, but they're immediately felt, so they're subject to more post hoc ergo propter hoc judgments. It's possible that more people will stop taking statins because of that part of the warning to cancel out the public health good that it might do otherwise.

Comments (12) + TrackBacks (0) | Category: Cardiovascular Disease | Regulatory Affairs | Toxicology


COMMENTS

1. Anonymous on February 29, 2012 2:22 PM writes...

It may be that it is not a matter of statistical strength based on the population size. Instead as per your points above, it may be that the incidence of such occurrences may only appear after years of statin therapy. Especially with comparatively higer incidences of dementia.

Therefore, "strong enough signals" to act upon, but action or understanding was delayed for the 1-2 decades after statins were introduced. Notice the interesting recent data on multigenerational effects of DDT and other molecules. Is measuring statin effects 40 years ahead, down the line for children and grandchildren of patients?

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2. NoDrugsNoJobs on February 29, 2012 4:06 PM writes...

Unfortunately, the importance of secondary markers versus outcomes seems to vary depending on whose doing the reporting and setting the requirements. Type 2 diabetes is a characterization of blood glucose. High blood glucose much like high cholesterol is a proxy for other bad things but doesn't necessarily correlate overall for any given individual. Therefore, if one comes out with a drug that lowers blood sugar but has other effects, as all drugs likely do, the question all would want to know the answer to is how does that effect translate to heart attacks, strokes, blindness, etc. Statins dramatically lower cholesterol but the same question was asked and has been answered by many, many clinical studies....they reduce strokes, heart attacks, cardiac procedures, etc. In other words, regardless of what the effect on blood sugar is in the whole, the effect on outcomes is quite clear.....statins help those at risk of heart attacks and strokes including many with diabetes type 2 as their only risk factor who have been tested and benefited on statins as well. Therefore, if you would give a statin to somebody who already has high blood sugar and it has been shown to benefit that population, the outcomes of the drug clearly outweigh the harm in controlled clinical studies. The blood sugar effects have been known about for some time and were most prominent with high dose, potent statins such as crestor in the jupitor study. When they say risk of diabetes is increased, they mean risk of blood sugar increasing over a certain limit, it does not mean it is permanent and moreover, it is not an outcome and doesn't necessarily translate into an outcome. The sad thing is that when the media trumpets this info, there will be a certain number of people who stop taking their drugs. When you look at CV deaths over the last couple of decades, the impact of statins, stents, blood pressure meds, etc is amazing. for a society that is obese and sedentary, we are especially fortunate to have these drugs....

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3. John on February 29, 2012 10:47 PM writes...

What percentage of statin users would derive equal benefit from diet & exercise intervention? 90%? More? Drugging lifestyle diseases is a bad idea.

Cholesterol's predictive value in isolation is also overstated. There are many healthy nonagenarians with high HDL/TG. Three in my immediate family alone..

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4. researchfella on February 29, 2012 11:07 PM writes...

Yikes!!! I've been taking Lipitor on a daily basis for almost twenty years...! Or, wait a minute, how long has it been? Actually, am I getting this confused with some other medication? I'm pretty sure I'm still taking Lipitor... My mind is a little fuzzy on the details....

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5. Jose on March 1, 2012 7:23 AM writes...

Oh sweet irony! By developing such highly effective drugs, you can extend lifespan to such a degree that you then get nailed by exceedingly rare AEs that would never, ever show up in a clinical trial! Maybe it's the wave of the future?

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6. Moneyshot on March 1, 2012 9:19 AM writes...

I can sense the layers circling in the waters already........ Have you forgotten that you have been injured by a drug? Call us!

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7. NoDrugsNoJobs on March 1, 2012 9:57 AM writes...

I was just thinking the other day about the constant exhortations that diet and exercise would cut out the need for drugs such as lipitor. As far as I know, we have little more than observational data to support that. Where is the evidence? Do people who exercise have less heart attacks because of the fact that they exercise or are people who exercise more healthy to begin with? Older people who exercise tend to be wealthier and also have access to better medical care. We used to think that estrogens prevented heart attacks because huge observational studies supported that - the WHI study and a couple others done with placebo control showed that wasn't the case. hard to prove with exercise because you probably can't placebo control it very well. So what do we rely on?? improvements in blood pressure, cholesterol. Interestingly, those things alone are not enough to get a drug approval, rather we need outcomes. At the same time, I can't even begin to think how many times I've heard that exercise can replace statins or blood pressure meds or whatever. Without a double blind placebo controlled study., we'll have to accept the importance of secondary markers like blood pressure and cholesterol for the truth in that staement- the same ones the fda will not accept in isolation for drugs. Ironic.......

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8. Kent g. Budge on March 1, 2012 2:04 PM writes...

When I was first diagnosed with Type 2 diabetes (initial A1C 13.6, over twice normal), I began losing weight as quickly as I safely could by severely restricting calories and greatly ramping up my exercise level. But I also started taking glipizide and a low dose of Metformin.

Worked wonders. Two months later my A1C was back down to 5.7, within the normal human range. Was it the weight loss, the exercise, or the drugs? I think the best answer is "Yes."

I'm still on metformin but have dropped the secretagogue. I didn't like the cardiovascular safety profile, and my doctor agreed that two oral antihyperglycemics was probably overkill.

I started taking a statin a few months after that, when all the lifestyle changes still wouldn't budge my good/bad cholesterol ratio. (My cholesterols aren't too bad, except the good cholesterol is quite low -- this is probably familial.) Certainly the studies on the benefits of statins for diabetics had their effect on my thinking.

Curiously, my blood sugars seemed to go up slightly after I started the statin, though only for the first couple of months. Not a terribly meaningful anecdote, but I recall at the time reading that there were suspicions statins might slightly increase blood sugar, and making the decision that the benefits were worth the slight cost in sugar control.

And there's always the off-chance the gods will smite me for my pride by causing me to be run over by a truck tomorrow. There are no guarantees in life.

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9. HelicalZz on March 1, 2012 3:06 PM writes...

Just wait until the data mining of medical records reveals more and more of these low event associations. Will we need segregated systems to validate / confirm the discovery of data mining.

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10. SteveSC on March 1, 2012 3:17 PM writes...

Is it just coincidence that this all comes out only after most of the statins have gone generic? What do you think the chances are that one or more pharmacos are going to come out with a 'new, improved' statin 2.0 that doesn't show these problems (yet)?

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11. Design Monkey on March 1, 2012 3:57 PM writes...

>Is measuring statin effects 40 years ahead, down the line for children and grandchildren of patients?

Well, generally one starts nomming statins later in life, when they already are done with child producing. So effects on grandchildren might be not especially pronounced.

Permalink to Comment

12. William staton on August 24, 2012 2:11 PM writes...

I had all of the classic muscle pains listed in statin side effects. My doctor said it was because of coQ10 and vitamin D deficiency from the statins. She recommended StatinHelp that is sold on Amazon. It has really helped with the muscle pains. Statin side effects are never really discussed by the doctors. I found out TWO years into treatment when I mentioned needing something for back and leg pain to her. Thankfully she was a runner who believed in vitamin supplements.

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