'Statins' - nothing but slow poison?

[Perpetual Student]

It's because one study was observational and the other was from randomized, controlled trials. A drop of 50% is actually weak for observational data. It isn't strong until you see 90% or more. It's easy for selection biases or confounding to lead to differences of 50% or less. Those biases are removed (or at least reduced) in RCT's.

This is the same drop that we saw for hormonal replacement therapy and heart disease or vitamin E and cancer, both of which later were shown in RCT's to have the opposite effect.

Linda

Well. looking at this from the perspective of the science involved, a few questions come to mind. In a situation like this, is it expected that someone will review the procedures and analysis to discover where mistakes were made? I don't buy the arm waving statements that "such is the nature of medical research" or "observational" studies produce errors in the range of 50% to 90%. That is a huge error! In my business (the actuarial field), such errors with a population this big are unheard of. In the areas of science with which I am familiar, researchers would doggedly pursue duplicating or reproducing studies providing false results like this. Was the data manipulated? Were the researchers biased? Was the analysis sloppy? How is it possible to get and error of 50% when a large group like this is studied? Who is responsible? What kind of rubbish science is this? Accepting this kind of thing and simply indulging in arm waving seems to be incompetent and irresponsible! (Not you -- the medical research community)

 

[Skeptic Ginger]

I'm always a little confused by skeptics who refuse to be skeptical of the drug companies. Don't get me wrong; I'm not talking about being skeptical of the science behind pharmaceuticals. But saying I don't trust the drug companies isn't the same as saying I don't trust science. There's a huge profit motive for them to not necessarily always have our best interest at heart.

I don't know any skeptics who refuse to be skeptical of drug companies.

It just seems as though there are so many cases where the drug companies have either been caught in out-and-out deceipt, deception, hiding negative impacts, etc., or just been mistaken, not learning about a serious side effect until years after the fact. Or the fact that the overprescribing of antibiotics has become a serious problem with the rise of antibiotic-resistant bacteria. In light of those things, is taking a slower approach really such a bad idea?

There have been a few unethical drug company incidents. It doesn't mean the industry is rife with deceit anymore than seeing murders on the news means you aren't safe anywhere outside at night.

Overprescribing antibiotics has a different cause. It's not necessarily related to marketing antibiotics.

Now I will take a medication when it seems truly called for. I had a bad case of bronchitis a few years ago and took antibiotics for it. But I won't take a drug just for mild discomfort (didn't take any pain pills for a broken foot, but did for a broken tailbone) or for questionable benefit. I just figure anything that's going into my body and altering its chemistry may also be doing things I'm not so sure about. They almost all have some side effects, some of which can be serious, and many of which may not show up for years, or may not even have been discovered yet.

Does it concern you that you consume preservatives, that you breath in pollutants when you drive/ride in a vehicle, or that you wash your hair with shampoo? Who knows what that might do to you years from now?

I read a study just this morning that said something like 50% of Americans have taken at least one prescription medication in the last 30 days. I don't know, that sounds awfully high to me. Are we all really that sick?...

Table 94 on page 318. Prescription drug use in the past month, by sex, age, race and Hispanic origin: United States, selected years
1988–1994 through 2005–2008

If you look at the categories it includes everyone on birth control pills, people with asthma, hypertension, diabetes, heartburn, depression and so on. Yes, we are that unhealthy. There's no smoking gun here the way you imply.

Okay, you may now all commence to calling me an ignorant science-denier or a woo.

Are you one?

 

[fls]

Well. looking at this from the perspective of the science involved, a few questions come to mind. In a situation like this, is it expected that someone will review the procedures and analysis to discover where mistakes were made? I don't buy the arm waving statements that "such is the nature of medical research" or "observational" studies produce errors in the range of 50% to 90%. That is a huge error! In my business (the actuarial field), such errors with a population this big are unheard of. In the areas of science with which I am familiar, researchers would doggedly pursue duplicating or reproducing studies providing false results like this. Was the data manipulated? Were the researchers biased? Was the analysis sloppy? How is it possible to get and error of 50% when a large group like this is studied? Who is responsible? What kind of rubbish science is this?

This is why results from observational studies are treated with caution compared to those from RCT's. There are biases inherent in the data which are difficult to impossible to overcome, even in the absence of any fraud, error, biased researchers, or data manipulation. No matter how well done, the results can be unreliable, which means that the effect may not be present at all (the usual case), or it may even be in the opposite direction.

When we talk about interventions which are supported by lower levels of evidence (such as observational studies) and lack good quality evidence, our reluctance to recommend them and requests for RCT's are not for the purpose of simply solidifying the support which is already present or to become more precise in our measure of the effect. It is because we know that they are easily and often wrong, despite our best effort. You think it has to be because somebody did something wrong. It doesn't.

Accepting this kind of thing and simply indulging in arm waving seems to be incompetent and irresponsible! (Not you -- the medical research community)

We don't accept this. This is why the medical research community performs RCT's when assessing interventions. It's the alt-med community who wants to arm-wave away these problems and insist on recommendations on the basis of information which is quite likely wrong.

Linda

 

[Perpetual Student]

Well, it seems to me these guys at Boston University are getting an unjustified free pass. With this magnitude of error in areas of scientific research with which I am familiar, they would be "raked over the coals."

 

[fls]

Well, it seems to me these guys at Boston University are getting an unjustified free pass. With this magnitude of error in areas of scientific research with which I am familiar, they would be "raked over the coals."

Like I said, you seem to think that someone has to be doing something wrong to get these results. They don't. I realize this surprises people who are not familiar with medical research methods.

Linda

 

[Perpetual Student]

Like I said, you seem to think that someone has to be doing something wrong to get these results. They don't. I realize this surprises people who are not familiar with medical research methods.

Linda

What might surprise these people? The sloppy work? The lack of intellectual curiosity? The potential for dishonesty or fraud?

The researchers examined data from the Decision Support System database of the United States Veterans Affairs Medical System, a database of medical centers throughout the United States which contains diagnostic, pharmaceutical and demographic information on approximately 4.5 millions people.

Quite an impressive data base!

Using three different models for analysis, the researchers examined the effects of three different statins (atorvastatin, lovastatin and simvastatin) and found that simvastatin showed a strong reduction in the incidence of Alzheimer’s disease in each of the models. The data also showed the same statin was associated with a reduced incidence of Parkinson’s disease.

So, three different methods produced the same "strong" results -- but no one cares why this was a spurious result?

“The strength of reduction of incidence of dementia with simvastatin is striking,” said lead author Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM.

Why no follow up analysis in light of the NIH study? Has this person re-examined his results to determine how such a gross error could have occurred? Does anyone care?

Contrast this to the reaction of the scientific community when Fleischmann and Pons published their cold fusion results. The scientific community was relentless in its efforts to discover where the errors were made.

These people at B. U. claimed "strong" and "striking" results! What nonsense! There is no other area of science where these people would be given a free pass for such crappy work! Where is the scientific integrity? Where is the intellectual curiosity? Where is the professional honesty? Until those involved in medical research take a more aggressive approach to uncovering how such errors can be made, "science based medicine" will remain a marginal reality.

 

[casebro]

Who were "the researchers" mention in the quote in post 146?

The reason I ask is to see whether they were from the makers of simvastatin. The quotes don't say sim was better than the other statins, only that sim did something. And the quotes say nothing about how the patients were assigned the different drugs, age matching, etc.

Did I miss a link to that study?

 

[Emet]

Who were "the researchers" mention in the quote in post 146?

The reason I ask is to see whether they were from the makers of simvastatin. The quotes don't say sim was better than the other statins, only that sim did something. And the quotes say nothing about how the patients were assigned the different drugs, age matching, etc.

Did I miss a link to that study?

Yup. SG linked to it in post 134:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955446/?tool=pubmed

Competing interests
BW has a patent for use of statin as therapy for Alzheimer's disease.

 

[fls]

What might surprise these people? The sloppy work? The lack of intellectual curiosity? The potential for dishonesty or fraud?

No. Like I said before, it would be the effects that the strengths and limitations of various research methodologies have on the conclusions which can be drawn. When you are unfamiliar with these details, it is surprising just how important these details can become.

You clearly have not read the study. Instead of making accusations gleaned from a press release, please consider reading the actual article where they address (in quite exquisite detail) what sort of conclusions can be drawn and the strength of those conclusions.

Linda

 

[Perpetual Student]

No. Like I said before, it would be the effects that the strengths and limitations of various research methodologies have on the conclusions which can be drawn. When you are unfamiliar with these details, it is surprising just how important these details can become.

You clearly have not read the study. Instead of making accusations gleaned from a press release, please consider reading the actual article where they address (in quite exquisite detail) what sort of conclusions can be drawn and the strength of those conclusions.

Linda

I find your defense of the B. U. study laughable. From that paper:

The large numbers of subjects provides enormous power for analyses and the structure of the databases allows for prospective studies of incidence. The strong statistical power associated with the large number of subjects also enables detailed subcategorization of the cohorts, which can provide novel insights. For instance, the ability to subdivide statin users by each statin allowed us to examine the effects of three different statins: atorvastatin, lovastatin and simvastatin. The ability to track subjects over a period of time allowed us to examine incident dementia cases, which represents a significant difference from our previous study on statins, which examined prevalent cases [9]. The focus on incident cases in the current study avoided problems associated with some of the biases that can occur in studies of prevalence, and could explain the differences observed between the two studies [9]. In addition, the covariates provide some adjustment for confounding by indication.

and:

Conclusion
Simvastatin is associated with a significant reduction in incident dementia and incident Parkinson's disease. Atorvastatin is associated with a modest reduction in incident dementia that is of borderline significance when age is included as a covariate, but insignificant when other comorbid diseases are included as covariates. Further studies are required to determine whether this effect represents a biological action of simvastatin or an unanticipated statistical bias present in the DSS database.

and:

Results
We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, p < 0.0001) and 0.91 (CI 0.80–1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, p < 0.0001).

 

[fls]

I find your defense of the B. U. study laughable. From that paper:

and:

and:

I don't understand your point. The bits you quoted are quite accurate and reasonable conclusions which can be drawn from their well-done study. Yet I'm supposed to be embarrassed by it?

ETA: It doesn't look like you understand what the authors are saying (it will be directed to a knowledgeable audience, rather than a lay audience). I'd be happy to elaborate on any of the findings or conclusions which you think mean something disreputable.

Linda

 

[Professor Yaffle]

Note that "is associated with" does not mean the same thing as "causes".

 

[casebro]

If the one statin does something other statins don't, that is another datum in the theory that statins cause their benefits exclusive of the cholesterol theory.

 

[Perpetual Student]

Note that "is associated with" does not mean the same thing as "causes".

Yes. And Bill Clinton did not have "sex" with that woman.

 

[Emet]

ETA: It doesn't look like you understand what the authors are saying (it will be directed to a knowledgeable audience, rather than a lay audience). I'd be happy to elaborate on any of the findings or conclusions which you think mean something disreputable.

Linda

Anything that you'd care to elaborate on (other than what PY already stated) will be greatly appreciated... at least by me.

 

[casebro]

This from the Helsinki Heart Study: "In this study of patients with known or suspected coronary heart disease, no benefit from Gemfibrozil treatment was observed in reducing cardiac events or cardiac deaths. "

From here: http://www.drugs.com/pro/gemfibrozil.html

I sure can find lots of evidence that cholesterol is not the culprit anyhow.

I sure hope somebody is working on alternatives that use a better understanding of the mechanism that statins actually use. Anti inflammatory, anti-clot, and plaque stabilization I suppose.

 

[Skeptic Ginger]

This from the Helsinki Heart Study: "In this study of patients with known or suspected coronary heart disease, no benefit from Gemfibrozil treatment was observed in reducing cardiac events or cardiac deaths. "

From here: http://www.drugs.com/pro/gemfibrozil.html

I sure can find lots of evidence that cholesterol is not the culprit anyhow.

I sure hope somebody is working on alternatives that use a better understanding of the mechanism that statins actually use. Anti inflammatory, anti-clot, and plaque stabilization I suppose.

Well if you'd been paying attention years ago you'd know, dietary cholesterol has never been the key player, saturated fats that raise the body's own cholesterol has.

 

[casebro]

Well if you'd been paying attention years ago you'd know, dietary cholesterol has never been the key player, saturated fats that raise the body's own cholesterol has.

Yes but in other quotes/cites above, diet can only change the serum levels about 5%.

And every study I've seen regarding each particular dietary saturated fat, results were that " _____ fat is not linked to a rise in heart attack rates". Stearate, coconut oil...

My gemfibrozil pills contain stearate. I don't take them. I feel they are pretty useless. They may lower the cholesterol reading, but not much gain in actual end points. And they constipate me. My hMO would appreciate any gain in postponement of procedures, abut they are not eh ones who would suffer the side effects.

An aside: I once took Gemfibrozil. The medico prescribed a stool softener, which gave me diarrhea. Which made hemorrhoids rear their ugly heads. So the Doc gives me a script for prednislone suppositories. Sorry Doc, no more avalanches of medicine for me. First side effect, I quit.

I've lately worked off 30 pounds in 60 days. All while eating beef and pork, and my home made sausages made from a combination of the two. And veggies, stir fried in coconut oil. No choley meds. Total cholesterol down to 177.

Why do i eat coconut oil? It is the best source for medium and short chain fatty acids. And seems to help my myopathy. Seems one of the more common myopathies is related to the inability to break chains into small pieces. So medium chain oils are prescribed. I don't fersure know that is my problem, but coconut oil does seem to help my endurance. For sure, biopsy shows my muscle cells have stock piles of lipids, which is abnormal and means the cells are not burning them.

I read today that statins work by preventing lypolysis. Doesn't sound like what I need. And is probably the cause of the myopathic side effects of the statins.

So, what I am attempting to do is individualize my treatment. I'm thrilled so far.

 

[Skeptic Ginger]

...
I've lately worked off 30 pounds in 60 days. All while eating beef and pork, and my home made sausages made from a combination of the two. And veggies, stir fried in coconut oil. No choley meds. Total cholesterol down to 177.

I hope you can keep it off. Rapid weight loss is rarely permanent. But I support you in your endeavor.

...
I read today that statins work by preventing lypolysis. Doesn't sound like what I need. And is probably the cause of the myopathic side effects of the statins.....

Not sure where you read that. The mechanism of action for statins is easy to find and preventing lypolysis is not one of the mechanisms.

For a technical discussion of the mechanism of action see Statins: mechanism of action and effects

The beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic effects, that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert antiatherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.

For a slightly easier to understand discussion see the Wiki entry.

Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway. Because statins are similar to HMG-CoA on a molecular level they take the place of HMG-CoA in the enzyme and reduce the rate by which it is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol, as well as a number of other compounds. This ultimately reduces cholesterol via several mechanisms.
Inhibiting cholesterol synthesis
By inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night,[46] so statins with short half-lives are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in the short-acting simvastatin taken at night rather than the morning,[47][48] but have shown no difference in the long-acting atorvastatin.[49]
Increasing LDL uptake
Liver cells sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to draw cholesterol out of the circulation.[50] This is accomplished via protease enzymes that cleave a protein called "membrane-bound sterol regulatory element binding protein", which migrates to the nucleus and causes increased production of various other proteins and enzymes, including the LDL receptor. The LDL receptor then relocates to the liver cell membrane and binds to passing LDL and VLDL particles (the "bad cholesterol" linked to disease). LDL and VLDL are drawn out of circulation into the liver where the cholesterol is reprocessed into bile salts. These are excreted, and subsequently recycled mostly by an internal bile salt circulation.
Other effects
Statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. The ASTEROID trial showed direct ultrasound evidence of atheroma regression during statin therapy.[11] Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research):[51]
Improve endothelial function
Modulate inflammatory responses
Maintain plaque stability
Prevent thrombus formation

I don't see anything there that says, prevents lypolysis.


Also, it's the anti-inflammatory effect that was suggested as the diference between statins that was hypothesized as resulting in the difference in outcomes in the study in question which found simvastatin might decrease Alzheimer's while the other statins did not. However, I have not personally investigated this claim nor do I doubt Linda's assessment of the weakness of all the study results involving stains preventing Alzheimer's.

I believe anti-inflammatories were shown to have an effect on Alzheimer's in the Nun Study. But the timing and the regular use of anti-inflammatories several years prior to onset of symptoms was key to the prevention. Unfortunately this is unpublished data as far as I can find.

So far RCTs have not confirmed the results. I think it is interesting that the data in the Nun Study suggested the prevention had a key window period. IIRC it was that nuns taking anti-inflammatories daily in their 40s and 50s had less Alzheimer's disease but taking the anti-inflammatories in one's 60s and 70s did not show any effect. Unfortunately this is all from memory from a conference and as I said, I can't find the data online.

The role of anti-inflammatories in preventing Alzheimer's remains uncertain. Just as the results suggesting statins might prevent Alzheimer's, the results remain unconfirmed with RCTs.

 

[Soapy Sam]

Informative thread.

I now return you to anecdote country.

Back when I ran 4-5 miles a day (before the knees developed osteo arthritis), a nurse friend checked my cholesterol, in an attempt to get her couch potato hubbie to have his checked. She was shocked to find my blood cholesterol was offscale at the high end of the test, while his was in fact rather low. That's genes for you.

Simvastatin brought mine down from around 8 (I don't know the units-mmol/litre maybe?) to 5, but after about a year it went back up to 7+. Lipitor was substituted, with a similar pattern now apparent. It appears my Operating System runs in some sort of equilibrium way the hell up the high end - and actually reponds to statins by cranking out more . I'm now wondering what happens if I stop taking them. My mother has had a couple of strokes, but she is 86 . Father had a triple bypass at 58 (I'm 56) and died of an aortic aneurism, aged 70, after suffering dementia for 3 years.
Gradual withdrawal may be my the best option, though my GP wants to up the dose and see.
The point is that we're all genetically different, one size is unlikely to be the best fit for all and to make complex decisions we need to look at complex data, both across populations and as individuals.

One anecdote I heard criticising statins was that they caused elderly people to fall.
Now wait a minute.
Elderly people do fall- and often injure themselves severely as a result. A lot of elderly people are on statins.
A lot of elderly people own cats.
Clearly, big pharma is involved in witchcraft.