Effect Measure

We’ve written quite a bit about statins because there is evidence that these plentiful and cheap drugs may be useful in treating or preventing the innate immune system’s catastrophic dysregulation sometimes called “cytokine storm” (see here, here, here, here, here for a few examples). A new study now suggests that daily statin use by people under 75 may also lead to a significant (40%) reduction in cataracts. This from a study in Epidemiology of 180,000 patients seen between 1998 and 2007 in Israel:

Dr. [Gabriel] Chodick and his colleague Dr. Varda Shalev found that men aged 45 to 54 who took the statins daily to lower their cholesterol levels also lowered their chances of developing cataracts by 38%. For women of about the same age, the risk for cataracts was also cut dramatically, by about 18%.

Dr. Chodick has been studying the health benefits of statins for years. One of his recent studies, featured as part of a Time magazine cover story, showed that statins can reduce a person’s chance of dying from all combined diseases and conditions by 40% — something in the medical community called “all-cause mortality.” (ScienceDaily)

OK. This researcher is a statin enthusiast. I’m not quite convinced by the “all cause” story since people who take statins differ in lots of ways from those who don’t. But disease specific results are more convincing and I’m inclined to give some credence to the cataract story. While statins have a pretty good safety profile, they aren’t completely harmless. Like another common and cheap drug with a myriad of benefits, aspirin, some people run into deadly trouble with them on occasion and muscle aches and raised liver enzymes are not rare. Occasionally someone has impaired statin metabolism which allows high levels to build up and the muscle effect is much worse, sometimes leading to massive skeletal muscle destruction, which can be fatal.

The main medical use is to lower your cholesterol and they work by competitive inhibition of an enzyme, HMG-CoA [3-hydroxy-3-methyl-glutaryl-CoA] reductase. The statins look like, but aren’t identical to, the HMG-CoA substrate, which means they can tie up some of the enzyme but not produce the next chemical in the pathway, mevalonate. Mevalonate is at the head of a cascade that produces cholesterol, among other things. Yes, you manufacture cholesterol in your body. Most of your blood cholesterol isn’t from diet but is stuff you make yourself in your liver, mainly at night. When you make less cholesterol your liver freaks out and and starts to make more LDL (so-called “bad cholesterol”) receptors on the cell surface and this mops up more circulating LDL. A pharmacologic double whammy.

I take statins every day for its cholesterol lowering effect. It’s been pretty effective for that, lowering my cholesterol from 220 to 170 in a month.

It’s nice if they have other benefits too. As long as they don’t kill me in the process.

Comments

#1 Ed Whitney
February 12, 2010

The inhibition of HMG-CoA might also inhibit the synthesis of Coenzyme Q-10. Do you think it may be prudent for people on statins to take a Co Q-10 supplement? I do not know what data there might be on this question, but there seems to be some biological plausibility to the concept.
#2 revere
February 12, 2010

Ed; Not a clue. Anyone?
#3 NP
February 13, 2010

It has been postulated that CoQ10 depletion could explain some of the side effects associated with statins e.g. myalgia. There have been a few trials to see if CoQ10 supplementation helps reduce statin side effects, but they have conflicting results. I don’t know if CoQ10 supplementation has been adequately studied; it would seem to make sense for statin users to supplement, but unless we can be sure that there aren’t any deleterious effects, it has to be approached with some caution.
#4 Charles
February 13, 2010

Ah. Simvastatin. Just made the connection. I must have missed your posts about statins, or the open circuit in my brain would have closed faster.

I’ve been on this particular statin for at least the last two years. Sad to say, its protection against cataracts is less than total. I went to an ophthalmologist to have my eyes examined just over two weeks ago. I’m wearing one of the new pairs of glasses while I’m typing this.

But there’s an operation in my not-too-far distant future. Actually, two of them.

Yup. Cataracts.
#5 Caz fans
February 13, 2010

My mom was on statins; they exhausted her and made her weak. Don’t know if this was a mild version of myalgia or something else. She’s been switched to a niacin (the safe slow release version) and has no problem with it. I don’t know how her cholesterol has gone, but since she’s still on it after 6 months (with 3 month check ups) I suspect it isn’t bad.

It would be nice if they could predict ahead of time who won’t take well to statins.
#6 revere
February 13, 2010

Caz fans: This is not uncommon, unfortunately. Some people react this way to some statins and not others and some can’t tolerate them at all. There is a genetic factor that seems to affect statin breakdown and if a person doesn’t metabolize the drug as well as others it can lead to much higher levels that seem to be associated with the muscle problem. So maybe they will solve that problem. But one thing that seems to make statins so valuable for so many things is that they have multiple effects, many of which we don’t understand, much like aspirin (although a completely different kind of drug). If they didn’t have an extensive safety because a hugely prevalent use, I’d be more worried about what we don’t know.
#7 geridoc
February 14, 2010

We should be cautious about all these stories about statins reducing the risk for everything. These are almost all based on observational studies–not randomized trials. Till randomized studies are done, we need to be aware that all these reports are very very speculative.

The story of estrogen therapy should serve as a cautionary tale. While women who took estrogen seemed to have lower risks of just about everything bad, it was later shown this had nothing to do with estrogen—it was just because women who took estrogen had lower health risks to begin with. The randomized trials actually showed estrogen was harmful. We need to be careful because there are a lot of reasons to believe that people put on statins have some of the same characteristics that caused us to go wrong with estrogen.
#8 revere
February 14, 2010

geridoc: I have been doing a series on this (click sidebar tab under “scientific method” to see links). I do not agree that RCTs tell the story. They are often wrong, but for different reasons than observational studies. I am busy grant writing so I have yet to conclude the argument but I will at some point.
#9 antipodean
February 14, 2010

Geridoc

The problem with doing an incident cataract study would be the powering. You might well have to do it in Nepal or Bhutan or somewhere else they have appalling cataract incidence.
#10 Kevan Gelling
February 16, 2010

Do statins affect vitamin D levels?

Vitamin D production is positively correlated to cholesterol levels (1). Reducing cholesterol levels suggests that vitamin D levels will also be reduced. Are statin users more prone to vitamin D deficient morbidities?

——-
1. Bogh, M. K. B., Schmedes, A. V., Philipsen, P. A., Thieden, E. & Wulf, H. C. Vitamin d production after uvb exposure depends on baseline vitamin d and total cholesterol but not on skin pigmentation. Journal of Investigative Dermatology 130, 546-553 (2009).
#11 Kevan Gelling
February 17, 2010

Published today in the Lancet:

“Statin therapy was associated with a 9% increased risk for incident diabetes”

——
1. Naveed Sattar, N. et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet (2010) URL
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61965-6/abstract
#12 kimw
February 17, 2010

There was an interesting article in Slate 9/26/09 called “Treat Me?” by Darshak Sanghavi regarding absolute vs relative risk. Here is a part of the article:

In 1995, the prestigious New England Journal of Medicine published a study strengthening the case that otherwise-healthy men with high cholesterol should take cholesterol-lowering drugs called statins. Researchers in Scotland reported a 31-percent reduction in the risk of heart attacks among men taking the statin pravastatin, sold by Bristol-Myers Squibb under the brand name Pravachol. Due in part to this study, Pravachol became one of Bristol-Myers’ most profitable drugs and now grosses more than $2 billion in sales per year.

A 31 percent reduction in heart attacks, after all, seems impressive. Yet this pervasive way of describing clinical trials in medical journals—focusing on the “relative risk,” in this case of heart attack—powerfully exaggerates the benefits of drugs and other invasive therapies. What, after all, does a 31 percent relative reduction in heart attacks mean? In the case of the 1995 study, it meant that taking Pravachol every day for five years reduced the incidence of heart attacks from 7.5 percent to 5.3 percent. This indeed means that there were 31 percent fewer heart attacks in patients taking the drug. But it also means that the “absolute risk” of a heart attack for any given person dropped by only 2.2 percentage points* (from 7.5 percent to 5.3 percent). The benefit of Pravachol can be summarized as a 31 percent relative reduction in heart attacks—or a 2.2 percent absolute reduction.

There’s another instructive way to consider the numbers. Suppose that 100 people with high cholesterol levels took statins. Of them, 93 wouldn’t have had heart attacks anyway. Five people have heart attacks despite taking Pravachol. Only the remaining two out of the original 100 avoided a heart attack by taking the daily pills. In the end, 100 people needed to be treated to avoid two heart attacks during the study period—so, the number of people who must get the treatment for a single person to benefit is 50. This is known as the “number needed to treat.”

I distrust how the drug companies have been pushing statins without gold-standard double-blinded studies and proof of causative agents. I was not aware that there was proof that lowering LDL cholesterol levels was the means by which statins could reduce cardiac events in those who had already suffered one. Just a layman here, but would like to hear more from a source that I trust, such as Revere.

Yeah, I read Gary Taubes and once in awhile go to Michael Eades’ blog. Is he a crackpot, or not?
#13 kimw
February 17, 2010

Correction to the above: the article appeared in Slate in 2006, not 2009. Sorry.
#14 d
August 7, 2010

An Appeal for Support and Conformation of Adverse Effects

My daughter has lived with ALS like symptoms for almost 3 years. The worst of the symptoms began when her simvastatin was increased to 80mg in 2008.
Her MRI’s show LESIONS in the brain stem, specifically in the PONS area of her brain.
Of course, her 4 physicians refuse to believe that statin is involved. They are all satisfied with the diagnosis of “Ataxia”.

My Appeal is to all those who have similar brain lesions as shown and documented in MRIs. Please reply, or contact her father directly: Dr Stephen Arvay, stephenx11@cogeco.ca