Talk:Statin

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[edit] What's

What's your thinking on the use of the {{Statins}} template? It is currently only used on the Atorvastatin article, and does not even appear here. Is the thought generally that it should be used or should be avoided? If it should be avoided, should it be nominated for deletion?

Courtland 14:50, 2005 Mar 27 (UTC)

I think it's beautiful. Let's keep it. This means that links to these drugs in "see also" can disappear.

Perhaps you'd like to put the fibrates and the bile acid sequestrants in it as well! JFW | T@lk 19:08, 27 Mar 2005 (UTC)

I've added the template to all of the referenced articles.

Addition of the two additional items would require a change to the title, someting like "Hypercholesterolemia treatments". Do you really want to do that?

Courtland 19:38, 2005 Mar 27 (UTC)

The article currently reads:

Although statins inhibit endogenous cholesterol synthesis, their action goes further than that. By reducing intracellular cholesterol levels, liver cells upregulate expression of the LDL receptor, leading to increased clearance of Low-Density Lipoprotein from the bloodstream.

The second sentence states that liver cells reduce intracellular cholesterol levels, but I think what is meant is that statins reduce those levels, and liver cells react. AxelBoldt 00:14, 28 May 2005 (UTC)

You're right. JFW | T@lk 08:24, 29 May 2005 (UTC)

Axel, could you monitor when these statin/cancer results are published in a journal? I'm a bit allergic to New Scientist links when a peer-reviewed publication is available. JFW | T@lk 20:09, 30 May 2005 (UTC)

[edit] PPS -> statin myopathy

My source for this info is private communications with dozens of PPSers over the past three years. I have heard at least a dozen state that they experienced myopathic symptoms apparently due to statins, and have not so far encountered any who can say they've been on statins for more than a few months without experiencing myopathy.

Based on this, the probablility of statin myopathy in PPSers is probably in the 75-100% range, but I felt is best in the article to just say "higher than normal rate".

One could argue that the article should remain silent on this topic unless one can quote a published source, but PPS is receiving extraordinarily little research, and no researcher seems interested in the statin-PPS link. It seems unfair to the reader to omit this potentially important piece of information entirely.

On a slightly different topic, it should also be noted that statins can induce significant myopathy without producing clear signs of rhabdomyolysis (elevated CK and/or myoglobinuria). Since rhabdo is supposedly "infrequent", Drs are unlikely to attribute muscle symptoms to rhabdo without clear lab signs, even though the physical symptoms are there. I think the existing wording of the article is a little biased in this regard, by not mentioning myopathy and therefore downplaying muscle symptoms considerably.

(I want to note that I'm not a rabid anti-statin person. I understand the value of statins, and I'd be on them now if I could tolerate them, but I can't.) drh 14:27, 2 August 2005 (UTC)

See your talkpage, and please review this policy. JFW | T@lk 21:47, 2 August 2005 (UTC)

I've removed it for now. When you've published it, please let me know because it may well be worthy of inclusion. JFW | T@lk 01:08, 7 August 2005 (UTC)

With respect to ubiquinone comments that get deleted, there's ample testimony of Co-Q-10 users (ubiquinone) that benefit from supplementation, in terms of relieving CHF symptomatology and myalgias. References to follow with respect to CHF once I learn how to add them. There's a large multi-center Italian study for example. In the interim, you can call Dr. Peter Langsjoen in Tyler, Texas if you want to know more. Hubie59, 11-09-06

Hubie59, positive personal experience that has not been studied on a wider scale and not reported in a reliable source is classified as original research.The reason is very simple: many people have positive experiences with this, that or the other. But when the same remedy is studied on a larger scale, especially in a placebo-controlled context, one finds that it doesn't actually have any intrinsic benefit.

Of course Q10 supplements make sense, but we should not present it as "effective" until the trials have been reported. Statins took 8-9 years to become widely accepted, and then only because large studies such as the 4S showed a real statistical benefit. We should demand no less from Q10 supplementation. JFW | T@lk 20:49, 9 November 2006 (UTC)

Thank you for your comments, JFD. The Italian study had thousands of patients (4K? 5K?) and has corroboration with additional studies. (Elsewhere I mentioned Merck's patent re:ubiquinone in combination with statins). The drug companies and the FDA are quite the bedfellows. A multi-antigen vaccine--Pediarix--was approved by the FDA based on a study of less than 200 kids! "Large, placebo-controlled, double-blinded, well-designed studies" in a postmodern culture means whatever the holders of the purse strings intend it to mean. Statin users shouldn't hold their breath waiting for drug companies to study quality-formulated Co-Q-10 because, as you know, its unpatenable. With respect to the 4S study, (4444 men and women with a previous MI treated with simvastatin (Zocord®) or placebo. A 1994 study – Credited for ushering in the era of statins). There were 111 CHD deaths in treatment group and 189 CHD deaths in control group, which amounts to an absolute risk reduction of a paltry 3.5%. With respect to total deaths, there were 256 total deaths in placebo group and 182 total deaths in treatment group--an absolute risk-reduction of 3.3%! In other words, if 30 patients are treated for 5.4 years then 1 person will benefit. Moreover, the benefits were realized in men only; not women (25 women in the placebo group died (6%) and 27 died in the treatment group (6.6%). And with respect to cancer, there were 13 cases of skin cancer in treatment group and 6 cases in the control group. If this is one of their hallmark studies you can imagine how much the other studies weakened the case for statins. Hubie59 02:36, 12 November 2006 (UTC)

Which Italian study? Where did you make that comment about Q10 together with statins and would you care to repeat it? Simvastatin is now generic, and some clever company will no doubt combine it with Q10 for those people genuinely worried about this.

I dislike your conspiracy theory on a totally unrelated subject (a vaccine). Can we stick to the issue? I'm also not in the mood to do number crunching. What was the hazard ratio for skin cancer, and what was the 95% confidence interval? JFW | T@lk 17:27, 12 November 2006 (UTC)

Co-Q-10 with a statin? See Merck's patent #4,933,165. I suspect Merck's patent may block other companies from formulating a statin-Co-Q-10 combo product so we'll leave that to the attorneys to hash out.

Conspiracy theory? I mentioned the vaccine study only to point out the hypocrisy that surfaces occasionally with the "need more, larger studies" argument that's often put forth to thwart an opposing view. This is not too dissimilar from the "experts" that ignore non-mainstream "original" data solely because of alleged financial conflicts of interest. This should cut both ways. For example, when was the last time anyone said, "You can ignore the statin studies. Many of the study leaders appear to be lapdogs for the National Cholesterol Education Board (NCEB), as attested to by the fact they receive grants, consultant fees and honorarias from multiple drug companies. They just want the money." You don't hear that.

I too will leave the number crunching to the other statin and Co-Q-10 wiki-lurkers. I've left plenty of fodder (and have plenty more). Time is always in short supply. Hubie59 03:27, 13 November 2006 (UTC)

Your position is still not clear. Do you think statins are harmful pharmacological bombs designed to make money for drug companies? JFW | T@lk 21:04, 13 November 2006 (UTC)

Are statins "harmful pharmacological bombs?" If you take one and go amnesic or need Tylox to treat your myalgias you would be inclined to say "yes." If you have familial hypercholesterolemia with a LDL of 500 you would likely say "no." Are they designed to make money? That's what drug companies do isn't it? Seek to make a profit while providing a product that provides a benefit with acceptable risks. However, statin makers have effectively disqualified themselves as witnessed by the Merck patent, failure to grant equal footing to the pleiotropic effects, the spin spun into their commercials, etc. Hubie59 20:01, 17 November 2006 (UTC)

Amnesic? Your evidence, please.

Of course drug companies want to make money. They are not charitable foundations. Sorry. Even the Howard Hughes Medical Institute needs drug companies to effectively market drugs discovered by its scientists (see imatinib). That is not equivalent with the accusations you have been making.

Disqualified? In whose eyes? In yours? JFW | T@lk 21:57, 20 November 2006 (UTC)

[edit] Alzheimer

Someone has been inserting laboratory evidence of statin action on microglia in Alzheimer's models. This was, however, in a section on cardiovascular disease (Alzheimer's, while associated with atherosclerosis and low-grade inflammation, is not a cardiovascular disease). Furthermore, this was in an animal model, not in patients. Finally, the four points quoted are from Furberg's review (I will add the reference).

There is a wealth of research into statins for all sorts of conditions, from Alzheimers to anaplastic thyroid carcinoma. I think we should be sensible and only include the major avenues of research here. I am not apposed to an Alzheimer paragraph, but preferably in keeping with the style of the rest of the article. JFW | T@lk 10:33, 19 August 2005 (UTC)

A lot has changed in a couple of years. I think a section on memory loss associated with Statins should be added to this article. Particularly since tests have been developed that can distinguish between memory loss due to Alzheimer's and memory loss due to statin use. --Jmcclare (talk) 15:41, 13 February 2008 (UTC)

To this day, the evidence in support of memory loss associated with statins is strong but anecdotal. I would wait until results of well designed trials are available. It's true that if what happened with Vytorin ^[1] is an indication of the impartiality of pharmas, we may need to wait a long time to see those results. Still, a randomized controlled trial funded by NIH is currently analyzing the effect of low dose statins on thinking and other behavioral indicators ( http://statineffects.ucsd.edu/ ).AK Arakaki (talk) 23:45, 27 February 2008 (UTC)

Beatrice Golomb has been making noises for a very long time about cognitive effects of statins. The bottom line is that the Heart Protection Study did not find any changes on neurocognitive testing, and all negative reports are anecdotal (and therefore not "strongly associated"). Some studies have shown an improvement in Alzheimer's risk; I don't know whether ApoE phenotype has been factored into that equation. At the moment I continue to disagree with Jmcclare that we can say anything definitive on cognition and memory vs statins, and we might as well wait for some actual evidence. JFW | T@lk 00:54, 28 February 2008 (UTC)

JFW: I disagree with your calling "making noises" to Beatrice Alexandra Golomb's research on cognitive effects of statins. She definitely is a qualified researcher, Professor of Medicine @ U.C. San Diego, board certified MD with a PhD in neurobiology, and her research on statins and noncardiovascular endpoints is funded by a four million dollar NIH grant.

In my comment, I said "the EVIDENCE is strong but anecdotal", I think we all understand and agree with the "anecdotal" nature, by "strong evidence" I mean that there are several reported cases where: 1) patients on statins have severe concentration and/or memory problems, 2) that disappeared after stopping the statins and 3) reappear when they start the statins again. This is an very reasonable criterion for assessing causal association, i.e the adverse drug reaction abates with dechallenge and recurs with rechallenge (PMID 15148066). Anyway, I think we agree on waiting until results of well designed trials are available. AK Arakaki (talk) 16:40, 5 March 2008 (UTC)

[edit] Disambiguation: rat liver protein

Apparently there is a protein called statin expressed in rat livers (PMID 2246273). Yes, this confused me for a bit too. Should there be a disambiguation page?

Courtland -- I remember you from my AZ days!

--Andrew Clegg 17:37, 6 November 2005 (UTC)

[edit] Cancer risk

JAMA this week: no benefit but also no risk of cancer[1]. JFW | T@lk 08:34, 5 January 2006 (UTC)

Yes, but the article which cited the rodent studies viz cancer stated that long term studies are needed, and that until they are done, statins are not recommended for anyone other than those in immediate risk of heart attack. The JAMA round-up is not a round-up of *long-term* studies. It is rather misleading to state "no benefit and no risk" instead of "no benefit and no risk based on cume of short-term studies, however due to rodent carcinogeneity, long term studies are needed before risk is justifiable for anyone not in immediate danger of heart attack."

Cindery 02:16, 29 July 2006 (UTC)

PMID 8531288

That article is ten years old and has been superseded by enormous series showing no increased cancer risk and indeed a decreased risk of particular malignancies. JFW | T@lk 17:27, 12 November 2006 (UTC)

Jfdwolff, regarding the meta-analysis of 23 statin studies, a p-value of 0.009 is statistically significant, but I removed the "highly" that may be subjective. Now, about the "requires further investigation" statement, why do you think that a statistically significant higher incidence of cancer does not deserves further investigation? I mentioned this article in the cholesterol discussion page, but I haven't seen any objection against it since last September, so I brought it to the statins page, where it seems to fit better. —Preceding unsigned comment added by AK Arakaki (talk • contribs) 15:53, 27 February 2008 (UTC) I just realized what you meant by '"meriting further study" is WP:NOR', I apologize for my lack of familiarity with WP policies. I read the "No original research" page and understand that "requires further investigation" can be considered my personal interpretation. In fact, that was a conclusion from the authors, so I'll rephrase to make that point clear.AK Arakaki (talk) 16:11, 27 February 2008 (UTC)

I was misinterpreting your comment, I thought you didn't consider a p value of 0.009 as statistically significant. I agree that "significant" can be interpreted in other ways other than "statistically significant", I'll make similar corrections in my contribution to the cholesterol page.AK Arakaki (talk) 22:31, 27 February 2008 (UTC)

You shouldn't leave these comments halfway the discussion page. I hadn't noticed them. I'm glad we can agree on the use of the term "significant". JFW | T@lk 00:54, 28 February 2008 (UTC)

[edit] Ethics

"The issue of large asymptomatic populations taking a powerful drug, that most likely won't impact the chance that they will contract heart disease, is rarely discussed by physicians who prescribe the drug. As an example, if a group of 100 people all having a 10% risk for a heart attack in the next ten years start taking statins (reducing the risk of a heart attack by 30%), only the cardiac outcome of three people will be modified! Is it ethical to subject such a population to the risks of the various side effects, some of them serious, when many of those who will suffer from them would not have had cardiac problems anyway?"

While a discussion of medical ethics is certainly not something to be ignored, a better place for such a discussion might be medical ethics. However, the author's implied assertion that use of statins for prevention of cardiovascular disease is unethical is based on some flawed assumptions, thus I removed the section above from the main page.

The author cites an example of a group of 100 people with a uniform 10 year MI risk of 10%. In reality, the hypothetical population group members receiving statin therapy each have a minimum of 10% risk. And indeed, in Australia for instance, an individual is not usually considered for statin therapy unless he/she has a minimimum 5 year risk of 10–15%. Hence, although it is difficult to quantify, the benefit is greater than the purported "three people" in a hypothetical sample of 100 people.

Since it is impossible to predict precisely which individuals will benefit, the choice to treat for prevention of cardiovascular risk is a public health issue. Prescribers must balance risks of adverse drug reactions with the expected benefits. In this instance statins are well-tolerated by the vast majority of patients, and therapy is normally ceased in the minority of patients that do experience adverse drug reactions. From a public health viewpoint, the actual prevention of adverse cardiovascular events in a proportion of the group does outweigh the much smaller risk of adverse drug reactions. Additionally, the prevention of adverse cardiovascular events results in fewer patients requiring hospitalisation, freeing-up health system resources for other patients.

-Techelf 06:47, 14 April 2006 (UTC)

The same logic applies to 100s of other drugs. It does not belong here, that paragraph. JFW | T@lk 07:11, 18 April 2006 (UTC)

I *strongly* disagree. First off, an ethics section should be included in every drug entry, in my opinion, with general warnings about the unrelibility of medical studies due to unethical practices by pharmaceutical companies. Consumers/Patients should exercise caveat emptor--and perhaps be explicitly warned, by law or ethical imperative of Hippocratic Oath--that pro-drug studies may not be reliable or impartial.

Second, there is *particular* concern where this class of drug is concerned, as the estimates I have seen seem awfully high for how many people should take this drug and for how long. The profit motive for drug companies to compel such a colossal number of people to take these drugs every day at--what length, excatly?--renders them particlarly subject to skepticism/warning of potential unethical drug company practices.

http://www.guardian.co.uk/medicine/story/0,11381,1101706,00.html Cindery 02:23, 29 July 2006 (UTC)

I disagree that every drug article needs an "ethics" section, unless there have been explicit ethical concerns about that drug in major information outlets. Statins are better studied than any other class of drugs. Those questioning the impartiality of the trials would question the impartiality of any trial not conducted by themselves. JFW | T@lk 07:05, 5 September 2006 (UTC)

I would offer the following alternative to the above closing proposition: Those questioning the impartiality of the trials would question the impartiality of any trial not conducted by an impartial party. Impartial means no benefits are to be extracted by any stakeholder involved in such investigation. In particular, when a popular drug group such as this enjoys a mass market uptake, there is an equally vast audience to whom the issue of possible drug trial partiality is directly relevant. Certain drug types are more than an a mere academic interest; they are highy familiar to, and even ingrained in modern health culture. The consumer must not to be excluded from such discussion via the suggestion that ethics are not relevant to for example this particular subject of mass market drugs and their surrounding issues. Acssm 12:59, 31 October 2006 (UTC)

Again, this applies to many other drugs and not just the statins. Take it elsewhere. JFW | T@lk 00:54, 28 February 2008 (UTC)

[edit] Edits by Yankeedoodle and Jfdwolff

I happened to be reading this page out of interest, and wikilinked a paragraph by User:Yankeedoodle which was subsequently reverted by User:Jfdwolff, with well-motivated reasons. This is not a subject I have studied to any great extent, and I hadn't noticed the material I was wikilinking was a very recent edit by a new editor. However, after I noticed the previous edit had been reverted I was curious and did a search on pubmed.org for statin "beta blockers" mevalonate which had one hit [PMID 15577180] that is possibly the research YankeeDoodle was attempting to incorporate. The abstract suggests statins do supress mevalonate, but does not explicitly say that beta blockers do. A second search for mevalonate "Coenzyme Q10" again came up with one hit (!) [PMID 16286544] which directly addresses Jfdwolff's question by measuring how statins affect Coenzyme Q10 levels in a controlled study, although more research seems to be needed. My limited knowledge of these issues do not make me inclined to incorporate this myself at present, but it seems to be relevant and worthy of consideration. My unqualified conclusion is that Coenzyme Q10 supplementation for statin users would be worth considering for this reason alone. Elroch 15:22, 17 May 2006 (UTC)

One single PubMed hit for each? Boy, I'm underwhelmed. We need quite a few more. JFW | T@lk 19:27, 28 May 2006 (UTC)

Specifically: the Taguchi article is in Japanese, and the abstract does not indicate in which way β-blockade could possibly influence Q10 levels. As for Lamperti et al, the sample size was too small to say anything meaningful. There was no statistical difference in Q10 levels, and the statistical outliers could well have been the result of selection bias (a genetic propensity to low Q10, predisposing them to statin myopathy). When it comes to suggesting Q10 supplementation, I really doubt there are scientific grounds for recommending this to anyone. Does it even survive the gastric pH, or are you suggesting it is administered parenterally (intermuscularily, for example :-) JFW | T@lk 20:46, 28 May 2006 (UTC)

I am glad to be able to answer your last question from what I recall about CoQ10. Typically about half the daily requirement for CoQ10 comes from the diet and CoQ10 is a widely used supplement which is clinically proved to be have measurable benefits against several of the diseases of aging. Therefore I infer that it survives the stomach in substantial quantities. More information (supporting supplementation with CoQ10 in the elderly for several reasons) is given in CoQ10 at NIH, which seems relatively cautious about potential benefits. Elroch 11:02, 30 May 2006 (UTC)

The statement that Coenzyme Q10 is lowered by beta blockers (although not relevant here) is in the wikipedia article and although, as you and I agreed, a paper I referred to above said nothing about any effect, other research does say that the original statement was justified (for some beta blockers). [2][3] Elroch 00:10, 2 June 2006 (UTC)

Statins blocking the production of ubiquinone is well-established. Merck even got a patent combining statins with ubiquinone in the 80s-- patent #4,933,165. A cardiologist by the name of Peter Langsjoen of Tyler, Texas has had good results treating CHF patients with ubiquinone, inclusively. A large, multi-centered study done in Italy revealed a benefit in treating CHF with ubiquinone. I'll dig out the citation later. There are other favorable studies too.Hubie59 01:47, 12 November 2006 (UTC)

Please provide data before making further claims. You have already made significant representations of Langsjoen's view. JFW | T@lk 17:27, 12 November 2006 (UTC)

I'll not drop Langsjoen name anymore apart from citing specific references as requested. But if there's going to be consistency I suggest the statins wiki entry be rewritten so as to not falsely elevate the "importance" of lowering cholesterol, until more proof is available as to the influence of the pleiotropic effects. The article clearly imparts a greater importance on the lowering of cholesterol that is inconsistent with the available studies. Perhaps the drug companies trumpeting relative-risk reduction statistics is to blame here. Hubie59 03:44, 13 November 2006 (UTC)

In a world where absolute risk reduction is a rare commodity, statins are good at doing at least something. If all teenagers decided to stop smoking overnight, never to pick up again, more health effects would be achieved in the future than all the statins in the world could ever achieve, whether as primary or secondary prevention.

If this page presents lipid lowering in an overly effusive tone it does so in commission. A simple look at large guideline sites, or timi.org, will show that modern medicine seems to like lipid lowering and prefers to use statins. I agree that there are some issues (e.g. degree of lipid lowering seems to be subordinate to simply "being on a statin"). If you present papers that genuinely review the evidence (rather than just shouting "Merck and the FDA are bad") we can have an open discussion and try to make the article neutral and balanced. JFW | T@lk 21:04, 13 November 2006 (UTC)

Reviewing studies must take into account the integrity of multiple parties--the study leaders, whomever funds the things, past history of parties associated with the studies, etc.--this is nothing new to most. When you think about the travesty of pumping infants with thimerosal in the late 90s via vaccines, the Vioxx fiasco, the silence over the SV40 found in polio vaccines, the burial of the Merck patent combining statins with ubiqinone--and that 's a start--there's ample reason to emphasize Merck's motivation and the FDA may be share holder-driven more than anything else. Hubie59 01:04, 20 November 2006 (UTC)

I detect the agenda of a conspirationalist. "Pumping infants with thimerosal?" Please don't be so obvious, man. It hurts your credibility. JFW | T@lk 21:57, 20 November 2006 (UTC)

[edit] Safety

Bellosta S, Paoletti R, Corsini A: Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 109 (Suppl. III):50–57, 2004. I have no access to the fulltext. JFW | T@lk 19:27, 28 May 2006 (UTC)

The Italian study in support of ubiquinone (Co-Q-10) supplementation for improving one's congestive heart failure (CHF) status is entitled Italian Multicenter Study on the Safety and Efficacy of Coenzyme Q10 as Adjunctive Therapy in Heart Failure. It's in the Molec Aspects Med journal, volume 15 (supplement), pp. s287-s294, 1994. 0098-2997(94)00039-5. Hubie59 20:06, 17 November 2006 (UTC)

You mean PMID 7752841. Has it been replicated? Why are you relying on a trial >10 years old when there is good recent evidence for much more evidence-based treatments, such as ACE inhibition (SOLVD and many subsequent trials), beta blockade (BEST), spironolactone (RALES trial)... Why is Q10 holy and are drugs with clearly proven efficacy evil? JFW | T@lk 21:57, 20 November 2006 (UTC)

[edit] Mental effects

From the article:

Small studies have also raised the possibility of an effect on personality, according to articles published in QJM: the International Journal of Medicine and The Annals of Internal Medicine. Another article in Clinical Cardiology suggested the possibility of an effect on daytime performance. A review published in Pharmacotherapy noted a small number of reported cases of memory loss, recommending only that "Until causality is assessed in more rigorous studies, awareness of this issue may help clinicians better counsel patients and improve monitoring of adverse events."

162.119.64.111 (talk · contribs) keeps on insisting we cover material on the mental effects of statins. The above material is a collection of papers that address the subject. However, most of these are not notable to be included in a general scope article for the lay reader. For example, the QJM article covers six patients, as contrasted to the >20,000 in the heart protection study in which no neuropsychiatric deterioration was found. The Clin Cardiol article was about various sleep problems, something 162.119.64.111 grouped incorrectly under "personality".

It would be much better if we had a single systematic review that we could quote when it comes to neurological side-effects of statins. The stuff we've had so far is anecdotal.

162.119.64.111 is also advised to familiarise him/herself with WP:CITE. URLs are not acceptable for peer-reviewed journal articles. This article uses cite.php for the references, and it shouldn't be too hard to adhere to this. JFW | T@lk 20:49, 20 June 2006 (UTC)

162.119.64.111 responds: "It would be much better if we had a single systematic review that we could quote when it comes to neurological side-effects of statins."

I agree. In March I wrote that the statin entry "should at least mention research about the effect of statins on memory - even if it's only to point out it hasn't been proven. I added a placeholder line; feel free to polish as necessary." Instead the topic disappeared altogether. Let's work together to find an unintrusive way to mention this....

I understand that the benefits of statins may widely outweigh the disadvantages, but it bothers me that this article contains no mention whatsoever of any of these concerns. (The MRC's heart protection study wasn't specifically looking at memory or cognition; it was studying the effect on mortality and major morbidity.)

I appreciate the feedback; I'm new to Wikipedia. Please be patient with me. (I think the Clinical Cardiology article I cited was in fact about both "nighttime sleep and daytime performance," and was correctly placed in a separate sentence from the personality problems.) Again: let's work together. Unsigned by anon

There are several reports of cognitive dysfunction with statin usage. Dr. Duane Graveline wrote a book on this very subject. Even if the percentage of statin patients coming down with amnesia is small it's still worthy of inclusion in wikipedia. Chloramphenicol rarely caused aplastic anemia when it was in vogue but every good practitioner knew it could. How many statin users weren't told about statins and the possibility of amnesia after filling their prescriptions? For those interested, Graveline's book is entitled, Lipitor: Thief of Memory, Statin Drugs and the Misguided War on Cholesterol. Hubie59 02:00, 12 November 2006 (UTC)

Hmm, that's interesting. From the title of the book it seems that the book is more than just about cognitive dysfunction. What measures of cognitive dysfunction does he employ (MMSE, specific neuropsychological scales)? How large are his case series and why couldn't he publish his findings in a serious publication? I strongly doubt this should be included in Wikipedia, as I dispute the claim that Graveline's book is a reliable source (in view of his clear conflict of interest). JFW | T@lk 17:27, 12 November 2006 (UTC)

Why doesn't Dr. Graveline publish in a serious publication? I haven't met him but I imagine he recognizes the clear conflict of interest the major journal editors have (per the huge sums of monies they receive from runng drug ads) and has chosen to go the book route because of that. To elaborate, I suspect Pfizer, Astra-Zeneca and Merck wouldn't take kindly to journal editors publishing studies on patients going amnesic while taking statins, even if the percentage is quite low. Speaking of "clear conflict of interest," when you play that card against "non-serious publications" you discredit yourself by ignoring the same dilemma inherent with "prestigious journals." Will you be addressing ghost writers in the near future, or the amount of money that flows from the statin makers into the hands of the members of the National Cholesterol Education Board? Hubie59 01:06, 20 November 2006 (UTC)

Complot theories everywhere, huh? Now it's ghost writers! JFW | T@lk 21:57, 20 November 2006 (UTC)

Jfdwolff: I can't speak to the availability of peer-reviewed studies, but given that a lawsuit has been filed against Pfizer on behalf of two patients who claim to have suffered memory loss as a result of statin use [4], I think it's unequivocally worth including as "news" if nothing else. Also see this article [5] in Geriatric Times, and this story [6] from CBS News. All of this suggests that it's being discussed sufficiently to merit inclusion, which really should be the main criterion IMHO.

(Perhaps I'm a bit biased, in that my mother, father, and one of my closest friends have all reported dramatic cognitive/memory dysfunction whose onset and remission seemed directly linked to statin use and discontinuation. I appreciate your caution around Dr. Graveline, et al., but I really think this one's legit.) Goldenband 23:43, 26 April 2007 (UTC)

I agree we should say something about the cognitive effects of statins, if for no other reason than the fact that it has been the subject of a lot of popular press coverage. The two best peer-reviewed trials I'm aware of (PMID 10806282, PMID 15589485) both found small decreases in cognitive performance with statins, although the small size of the decrease was of questionable significance. Of course, those findings represent an average - it's possible that most people show no effect, but a small percentage who are susceptible have significant cognitive side-effects. There's also this (PMID 17253908), although it used a low dose (10 mg/day of atorvastatin), which is less than most folks get in practice. It's been awhile since I prescribed a statin, but my practice was to ask about cognitive side-effects and seriously consider stopping the drug if a person could relate problems to the drug. Other thoughts? MastCell ^Talk 01:57, 27 April 2007 (UTC)

Interestingly, there are trials underway to determine whether satins can be used to treat cognitive dysfunction, as in neurofibromatosis [7] (under cognitive disorders). See also pub med PMID: 16271875. 69.248.150.59 (talk) 14:50, 10 February 2008 (UTC)

[edit] Cataract

Incidence of nuclear cataract (the most common form) is reduced by a quarter in patients on statins[8]. JFW | T@lk 21:54, 20 June 2006 (UTC)

[edit] Cancer risk

I will chase fulltext for this JAMA meta-analysis (PMID 16391219), which addresses cancer risk in statin use. Effects seem to be neutral, with no benefit or risk for particular tumour types. JFW | T@lk 21:59, 20 June 2006 (UTC)

Leave me a message if you want me to send it to you as pdf. --WS 00:21, 21 June 2006 (UTC)

Statins don't cause cancer? Are we sure? There were 13 cases of skin cancer in the 4S treatment group and only 6 cases in the control group. In the CARE trial (Mevacor studied) there were 12 cases of breast cancer in the treatment group and just 1 case in the control group. Statins block squalene which has anti-cancer actions. In the ASCOT, PROSPER, WOSCOPS and LIPID trials non-melanoma statistics were either not tabulated or not reported.

Patients with a prior history of malignancy were excluded from the HPS trial (funded by Merck). Also in the HPS trial, there were 243 cases of skin cancer in simvastatin group; 202 cases in control group (20% increased risk of skin cancer [in terms of relative risk])

Statins haven't been around that long. Cancer can take time before its detected. Statin users under the impression these drugs may reduce their risk for cancer are misinformed. Hubie59 02:11, 12 November 2006 (UTC)

You have already cited the 4S skin cancer risk. HPS was indeed funded by Merck but performed by an extremely reliable research group that includes some of the UK's most eminent epidemiologists; don't you think it's rather cheap to discredit a study in this way? Again, could you also give us the hazard ratio and 95% confidence interval? Raw numbers without statistical measures are quite meaningless and just serve to inflame this discussion (as is obvious from the tenor of your responses). JFW | T@lk 17:27, 12 November 2006 (UTC)

A research group excludes prospective study patients with a prior history of malignancy in a srug that inhibits production of squalene and you refer to them as an "extremely reliable research group." Did these reliable researchers have any clear conflicts of interests? Hubie59 19:59, 17 November 2006 (UTC)

I've heard that canard before, and replied to it in the BMJ when Ravnskov and his buddies played their tape again. Every reasonable intervention trial excludes cancer patients because they confound the results. This is not in any way to be seen as discrediting either the trials or the researchers. Why is squalene so important in cancer? And why are you going on about conflicts of interest? JFW | T@lk 21:57, 20 November 2006 (UTC)

[edit] Borderline relevance

I removed the following two paragraphs:

In May 2005, results of an observational study of half a million U.S. veterans showed that people taking statins had a 50% reduced risk of developing any of several types of cancer. The authors state that this does not suggest that statins had a causal role in reducing cancer risk, as patients receiving statins possibly may also have benefited from unrelated health-related advice, such as stopping smoking.[9]
- This study has still not been published in a peer-reviewed journal, and I strongly doubt we should take a news article as a reliable source in a research area that is otherwise known for its emphasis on methodology.
In July 2006, a study was published in Hepatology which indicated that statins may inhibit hepatitis C virus (HCV) replication in vitro (PMID 16799963). Peculiarly, the anti-HCV effect is variable among the statins, with fluvastatin having the strongest effect and pravastatin having no effect. Hence, the anti-HCV effect is not associated with the statins' inhibition of HMG-CoA reductase.
- This is a laboratory study which has not been replicated in clinical practice. Yes, I'm aware some Australian outfit uses anti-cholesterol drugs for the treatment of HCV, but that's bezafibrate and not a statin. This should not be included against the much stronger clinical trials in humans that are available for citing.

If there is any disagreement we can always move this back, but for the moment it's all very nonstandard. JFW | T@lk 08:43, 20 July 2006 (UTC)

[edit] Critical voices

This article presently does not mention a small but noisy lobby that disputes the benefits of statins. Given that these people get their work published in mainstream journals (I even had a little exchange in the BMJ with Dr Ravnskov) they are probably notable, but I'd like to include a reliable source that sums up their views without dramatics. Is such a source available? Is it a source that is not just someone's website (both Uffe and Eddie Vos have big websites), and does it give a point-by-point summary of how they see the relationship between cholesterol and atherosclerosis, the risks and benefits of cholesterol lowering, and obvious problems with their approach (such as premature atherosclerosis in patients with LDL receptor mutations).

Anyone willing to provide such a source, preferable a bird's eye view by a non-committed observer? JFW | T@lk 10:20, 20 July 2006 (UTC)

A non-committed observer? Medically aware professionals spend their whole lives committing themselves to medicine. It sounds like you're making a suggestion that commitment to a cause automatically discredits one's position. In a world where people tend to either have great faith in the advice of their doctor, failing which little faith in the advice of their doctor, finding sources which are apathetic to both expert medical consensus and alternative perspectives to it might be a difficult thing. Acssm 13:50, 31 October 2006 (UTC)

That's not what I meant at all. I'd like to have a source that gives this "cholesterol critics" group a fair but informative treatment. Just relying on their own publications may not reveal the true picture. JFW | T@lk 17:27, 12 November 2006 (UTC)

Maybe not exactly what your looking for but there is a recent Lancet paper ^[2]. I'm in favor of a section that provides a critical response on the topic. —The preceding unsigned comment was added by 68.96.201.36 (talk) 02:34, 28 February 2007 (UTC).

[edit] "fungalbiotics"

hi, i reverted that because this is an article about statins, not about high cholesterol, per se. an experimental/minority view of the etiology of high cholesterol might have a place elsewhere, but please keep in mind that it is a minority view (i.e., probably doesn't need a whole paragraph) and that "fungalbiotics" is a neologism... Cindery 02:02, 5 September 2006 (UTC)

I agree, Cindery. I think this is a highly speculative theory with little support from anyone. Statins have been studied better than any other medical intervention in literally 100s of well-designed clinical trials. If we now come along with a poorly studied, unstudied and highly speculative theory, this completely degrades the article. Which fungi are we talking about anyway? Not Candida spp. I hope? JFW | T@lk 06:51, 5 September 2006 (UTC)

In response to "Cindery" below (comment moved here by JFW | T@lk): I have been adding the properties statins have as an antifungal, which is one of the reasons why they work. And people keep deleting it. Keep in mind that EVERYTHING is a minority view at one point or another. The world does not "wake up" one day and have a majority view. Either way - you can have your "majority" view. 71.204.83.198 (talk · contribs)

Welcome to Wikipedia, 71.204.83.198. Unfortunately we are not a crystal ball, and cannot predict which presently non-notable theory will become notable in the future when everyone has woken up.

Could you provide peer-reviewed studies into the properties of statins as antifungals? Are there any trials? What are the endpoints? Have fungi been demonstrated in atherosclerotic lesions in the same way as Chlamydia spp.? One needs to remember that all big trials looking at antibiotics for atherosclerosis have not shown any benefits. JFW | T@lk 06:59, 5 September 2006 (UTC)

One of the things that makes Wikipedia so great is: the ability for people to disseminate information which is relevant - even if some people don't agree. One of the biggest problems with Wikipedia is: the ability for people to delete information which they think is not relevant – even if some people disagree.

The mechanisms by which cholesterol works in the body is (as is all medicine) a constantly changing "science.” The best medical practice today is tomorrow’s joke, as it is with virtually all professions in a growing civilized society.

My information about the relationship between cholesterol, mycotoxins and statins may be a minority view but one supported by studies of the mycotoxin cyclosporin, cholesterol and statins. I added this reference because I thought I would get your attention or at least give a moment of pause before my contribution was summarily deleted as unverifiable - not just truth (a requirement of wikipedia) – I was wrong.

If you don’t agree with something that you think is wrong – but cannot prove it is wrong – the best course of action is to edit the page and move it to a different section marked “minority view” or something similar. This would serve all our interests and note the contributions of others to this endeavor called Wikipedia - and possibly enlighten readers as to verifiable alternatives. Unless, of course, somebody here is on the pharmaceutical payroll. This is also a problem with Wikipedia.

As for citing studies – I might do that when I get the impression somebody will listen. No offense taken.

I need not be introduced to the virtues of Wikipedia. I also agree that not everything should be deleted, and I even agree that science is constantly changing. But your contributions were inconsistent with two key policies that determine Wikipedia content: WP:NOR and WP:NPOV. NOR determines that original research should be published elsewhere before it merits inclusion; perhaps adding a reliable source would have avoided that problem. NPOV determines that the encyclopedia should be neutral in summarising different views, and makes a provision for those views that are simply not significant (yet). I also quoted WP:NOT, which states quite clearly that "Wikipedia is not a crystal ball" - there is no way of knowing whether your theory will stand the test of time.

I will happily review whatever source you provide on this talkpage and see if the revised material meets the requirements outlined above. JFW | T@lk 20:41, 10 September 2006 (UTC)

[edit] May want to reference this

Medscape article: Systematic Review of Statin Safety

http://www.medscape.com/viewarticle/550619

(I don't know if it can be referenced without a Medscape registration, but the registration is free.) drh 02:21, 25 January 2007 (UTC)

[edit] "Natural" vs. synthetic

I removed a statement to the effect that natural (fermentation-derived) statins are more effective at LDL-lowering than synthetic statins. First, it wasn't supported by the reference provided; second, it's just not correct. Atorvastatin, a synthetic statin, is one of the most potent in terms of LDL-lowering. Interestingly, this article (PMID 11583643) cites the same editorial I removed as supporting the fact that natural and synthetic statins are equivalent. So I removed the statement. MastCell 23:56, 9 February 2007 (UTC)

[edit] Perversion of the Healthcare system

(based on the Jan 20 Lancet article) Current guidlines call for 39 million americans to be treated; this wll cost billions of dollars, and many of these people will be taking statins for decades. Given this, it would seem a priority for the national health care system to establish that statins actually do good; yet the lancet article suggests that for many people there is NO BENEFIT, ie, statins cause as much harm as good. One could argue that this belongs in a seperte article, on how the profit motive distorts the health care system in the US, or something like that, but since statins are the lead example of this phenomenon, I think it should be part of the statin article. —The preceding unsigned comment was added by Cinnamon colbert (talk • contribs).

The Lancet article is already cited. An article describing "how the profit motive distorts the health care system" would be an opinion piece, and probably suitable for many venues, but not Wikipedia. Discussion about lipid treatment guidelines and attributable opinions on them is probably best dealt with in depth at cholesterol, coronary artery disease, primary prevention of heart attacks, hyperlipidemia, etc. MastCell 00:54, 11 March 2007 (UTC)

[edit] Furberg reference

In reading this article, I found a citation that had no information in it. Looking at the text, it was listed as <ref name=Furberg/>. There was no earlier reference to any work by Furberg. I found the following article by Furberg, which seemed to provide the information cited. I added this to the citation.

Furberg, Curt D. (1999). "Natural Statins and Stroke Risk". Circulation 99: 185-188. American Heart Association.

Please correct/revert me if this is incorrect. — ERcheck (talk) 15:13, 4 March 2007 (UTC)

That is correct. I originally added this reference. I wonder how it got removed. JFW | T@lk 23:48, 7 March 2007 (UTC)