Some statins cross the blood-brain barrier (see below) and therefore potentially can affect brain function. They reduce cholesterol concentrations and cholesterol is an essential component of cell membranes, including neurons in the brain. There are a large number of individuals reporting memory problems in reply to articles in the WSJ, in which a doctor was quoted as saying “Lipitor makes women stupid,” followed by an article in the NY Times . In 2003 an article cited 60 reported cases of memory impairment, most commonly with Zocor, less with Lipitor and only one case with Pravachol. Since Zocor is the most lipophilic (meaning most likely to get into the brain) and Pravachol is not lipophilic, this pattern is consistent with a relationship between statins and memory problems. Half had the onset of memory problems within two months of starting statins. Most (56%) patients improved when they went off the drug, and there were four patients who had memory problems return when they went back on the drug. Muldoon and colleagues writing in 2000 reported on 209 healthy adults treated with Mevacor (lovastatin) or placebo for cholesterol reduction. Mevacor treated patients had significant reductions in attention and psychomotor speed compared to placebo treated patients.

These problems are the inevitable result of a push to give statins to people with normal cholesterol concentrations. This is in my opinion a cause for concern. For one thing, we are introducing medications with potentially dangerous side effects to people who do not have a disease. Secondly, cholesterol is a normal part of the body and is required for a number of processes, like the construction of cell membranes. Very low cholesterol concentrations have been linked to depression and suicide.

Statins also may increase the risk for depression. Cholesterol is the essential building block of neurotransmitters and hormones, changes in which have been associated with the development of depression. This may explain why many patients feel so much worse when their cholesterol is lowered. Statins increase the risk of a return of depression in patients previously treated for depression; if you take a statin after being treated with an antidepressant, your risk of having the depression come back is 61% compared to 40% if you didn’t take a statin (Steffens et al 2003).

Steffens DC, McQuoid DR, Krishnan KRR (2003): Cholesterol-lowering medication and relapse of depression. Psychopharmacology Bulletin 37:92-98.

A doctor developed such severe problems with memory that he wrote a book about his experiences called Lipitor Thief of Memory

As usual the medical establishment is rushing to say that there is no association between statins and memory problems. The medical consultant to abcnews.com said he had to set the record straight and say that the “benefits outweigh the risks”. A doctor who said “Statins make women stupid” was said to have made “inflammatory” comments. “Inflammatory” to who? Pfizer’s business plan?

Originally posted here; follow link for original links to articles.

My book ‘Before You Take That Pill: Why the Drug Industry May be Bad for Your Health: Risks and Side Effects You Won’t Find on the Label of Commonly Prescribed Drugs, Vitamins, and Supplements’ is now available at amazon

OK, so far so good.

However there are a number of problems with the conclusions not to mention the multiple pharma conflicts of many of the authors that may have contributed to those distorted conclusions.

In the conclusion section, they incredibly report a 12% reduction in mortality with no mention of differences by sex or diabetes status. They go on to write ”no significant treatment heterogeneity was found between the sexes, in elderly and young people, and between people with and without diabetes.” However inspection of Table 3 shows that there were in fact no statistically significan reductions any endpoint (mortality, heart attacks) in women or diabetics or people over age 65. Furthermore, there was no mention of number needed to treat (NNT), or the fact the number of people saved from a heart attack were not greater than those developed liver problems or severe musle pain (which could lead to rhabdomylosis, possibly fatal). Or that the 12% relative reduction is equal to about a 1% absolute reduction.

This misrepresentation of the results is bordering on fraudulent.

In this procedure doctors put in a guideline in the coronary arteries and blow up a balloon that flattens plaque against the wall of the artery and opens up the artery or they insert a stent to keep the artery open. Sound good and makes sense, too bad it doesn’t work.

“There are people in the cardiology community who don’t believe the results. They don’t believe it applies to the patients they see,” Dr. Judith S. Hochman, director of the Cardiovascular Clinical Research Center at New York University School of Medicine, was quoted as saying. “So we still see a lot of angioplasty being done without patients really understanding that it will not reduce their chances of heart attack or death.”

But I’ll give the reason why they still perform 1.2 million of these procedures every year. It is pretty simple really. Greed.

Nancy Nielsen MD, President of the AMA, opposes healthcare reform

Doctors always say things like they don’t believe the data, or that isn’t the way it is in my practice. Since they won’t believe in science, data or reality, maybe we should just play their game and use some wizadry to get them to do the right thing and stop doing these useless procedures.

When I count to 3 you will stop performing angioplasties

Or maybe one of the Obama guys should have some guts and stand up and say we’re not gonna pay for those things anymore.

[Update: see comments section for reference to acute coronary events where PCI has demonstrated efficacy and citation by Marilyn Mann which was made immediately after I posted this on June 25 which I assumed was sufficient for anyone reading this; that didn't stop a cardiologist in another blog from going on the attack and saying that since the COURAGE trial showed lack of efficacy in reducing heart attacks in stable coronary disease these procedures have declined. Even so they are still estimated to be about 1/3 which is too many and some cardiologist lately have gone to jail for performing PCI on people with little or no heart disease. So my initial statement that 25 billion dollars could be saved is not correct. It is more like, um, 8 billion.]

We believe that the treatment benefits achieved in the JUPITER trial are not large enough to advocate an expansion in the clinical indications for statins. The potential implications of this trial for a change in clinical practice are further limited by a lack of information on the long-term risks and benefits of statin therapy in predominantly healthy individuals. Unfortunately, it is unlikely that we will be able to gather these data in the future. Because sponsorship of major treatment trials is almost exclusively left to the pharmaceutical industry, it is doubtful that another trial will be carried out, with sufficient sample size and proper follow-up, to study the effects of statin treatment in such healthy individuals.

And we go on:

Perhaps the most important lesson to be learned from this trial is that extreme caution should be placed in deciding to terminate early an industry-sponsored trial, such as JUPITER. At the current status of knowledge, behavioral prevention strategies remain the best investment for the prevention of cardiovascular disease and its risk factors in predominantly healthy individuals.

Don’t get me started on my father-in-law, who is becoming increasingly deaf at the age of 89, and who isn’t as perky as he used to be, and who ‘stopped working’, therefore his Italian physician has brilliantly put him several different psychotropic medications for a “pochino depression”.

Is that in the DSM? Should that be under consideration for the DSM Shadow Team?

Anyhoo now my brother-in-law has now been prescribed Cardura for high blood pressure (what is it with these Italian physicians and Cardura? They must be giving out some really great pens or maybe something even better. Hmmm…). He told his physician about what I had written about Cardura and his physician’s response was:

Those American physicians make a lot of mistakes.

Humph.

Another news item from Italy this week is related to the earthquake that flattened much of the city of Aquila and the region of Molise. BTW thanks guys who were asking about me. The Italians fearless leader, Silvio Berlusconi, after seeing the 28,000 people who were living in tents, made the brilliant comment:

They should try and enjoy themselves and pretend they are camping.

This from the guy who made a former topless model and “showgirl” a member of his cabinet, a woman he said he would marry instantly if he wasn’t already married. Which led to his wife demanding a public apology in one of his newspapers. Which he gave. Oh, he also said Obama had a “sun tan”.

Silvio Berlusconi relaxing with cabinet member Mara Carfagna

I swear I am not making this stuff up.

The interesting thing about his ‘camping’ comment is that although this idiotic comment made the front page of the London Times, there was not one word in the Italian papers. Maybe that is because he owns all three major TV networks and had influence over the newspapers and other media outlets as well. You know how Jon Stewart likes to lampoon government leaders? The last comedian to make fun of Berlusconi on TV ended her show with “see you next week… maybe.” That was back in 2003 and we haven’t seen her since. Berlusconi’s government replied that the Times should have written about how the earthquake victims clapped for Berlusconi. Maybe we should get Sarah Palin to clap into the microphone with them.

Anyhoo since presumably the majority of Italians voted for this clown (three times??), and since he is right wing presumably a majority of physicians, who are they to say that we make ‘alot of mistakes’?

In this paper the authors point out that many studies that are used to argue that salt reduction has no effect on hypertension or health are studies in which the salt reduction only occurred of the course of one week, or involved acute salt depletion. The authors point out that one week is not long enough to evaluate the effects of salt reduction, and that acute salt reduction leads to an activation of the sympathetic nervous system, which leads to an artificial increase in blood pressure. Sounds good to me so far, guys.

They listed 17 trials of people with hypertension and 11 trials of people with normal blood pressure that were conducted for four weeks or more and had adequate salt reduction (4.6 g per day) as measured by excretion in the urine. People with hypertension had a 5 mm Hg point drop in systolic and 3 point drop in diastolic. People with normal blood pressure also showed a drop to a lesser extent. The authors note that this amount of salt reduction would result in a 14% drop in strokes and a 9% drop in heart deaths.

Clinical trials of dietary salt reduction and high blood pressure

Unfortunately noone has done a randomized trial of low salt versus high salt diet and it is unlikely to happen now due to ethical issues. Mrs. Bremner points out that increases in salt in the diet lead to a craving for salty food that causes a vicious cycle, which is one way people may become addicted to salty junk foods and snack foods.

Dr B.’s comment: It looks like cutting down on salt does lower blood pressure although a 14% relative reduction in cardiac events may not be that big of a deal in terms of absolute reduction of risk for a single individual. Salt may be just part of the problem with junk food. There was a study showing that people who eat in fast food restaurants three times a week have a greater than 90% risk of getting diabetes or heart disease and I need to find that reference again.

An analysis of the published literature of people without heart disease examined a total of 51,342 women and 44,114 men from a range of studies who did not heart disease but had risk factors for heart disease (Berger et al 2006). Daily aspirin in women reduced cardiovascular disease by 12%, which was statistically significant, with a 17% reduction in stroke and no effect on heart attacks or cardiovascular mortality. However for any given woman, the absolute risk reduction, or how much the risk of heart attack was reduced in that individual, was only 0.3% over a six year period. And aspirin increased the risk of major bleeding by 68%. For men there was a 14% reduction of cardiovascular events primarily related to a 32% reduction in heart attacks with no effect on strokes or cardiovascular mortality. That translated into a .37% absolute reduction over a six year period. And men had a 72% increase in major bleeding. Aspirin did not save any lives in men or women. And as pointed out by Mrs. Bremner for every stroke in women or heart attack in men that is prevented by aspirin, there is one major gastrointestinal bleeding event caused by aspirin.

For men with a history of heart disease, taking baby aspirin every day can reduce your risk of death from heart disease by about 17% (ATC 2002). Translated, this means you are reducing your risk by about 1% per year. Although technically the risk of stomach bleeding is outweighed by the heart benefits of aspirin (which can only be shown when large numbers of patients are studied), in terms of what that means to you the differences are clinically meaningless.

In patients with strokes or transient ischemic attacks (TIAs) aspirin plus dipyridamole (a blood vessel dilator) was shown to be associated with a 13% rate of cardiovascular event compared to 16% on aspirin alone, a difference that was statistically significant (Esprit 2006).

Overall, I think aspirin for disease prevention is a bunch of hooey invented by cardiologists. My father almost died from bleeding from taking aspirin for such a purpose.

A friend of mine used the aspirin story to illustrate how incredibly weak some clinical trial data really was.

ATC (2002): Antithrombotic Trialists’ Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. British Medical Journal 324:71-86.

Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL (2006): Aspirin for the primary prevention of cardiovascular events in women and men: A sex-specific meta-analysis of randomized controlled trials. Journal of the American Medical Association 295:306-313.

Esprit (2006): Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. The Lancet 367:1665-1673.

Hat tip to CDC Mole.

New New! Lolcat! I done wanna die!

This study looked at 63,469 women in the Nurses Health Study who didn’t have a history of heart disease, divided them into different levels of depression based on the self report Mental Health Inventory, and then followed them over several years. They found the usual associations between depression and risk of heart attack, but what was more interesting was the fact that women on antidepressants were three times as likely to have a sudden cardiac death than women not on antidepressants. This was pretty striking, and was not accounted for by other factors such as risk factors for heart disease. Granted, sudden cardiac death in healthy women is fairly rare, and in this study only 46/100,000 women on an SSRI had a sudden cardiac death.

Tricyclics have long been known to prolong the cardiac Q-T interval, so they could theoretically cause ventricular arrhythmia, leading to sudden death. The SSRIs have been promoted as being safer from this standpoint, however in the current study there were not any differences between SSRIs and “other antidepressants” in terms of sudden cardiac death.

The graph below shows the risk of sudden cardiac death over time. It is called a “survival curve” and shows what percentage of the women had died up to that point of time. The women who were most depressed and on antidepressants are the blue line; they were most likely to die. Behind them are nondepressed women on antidepressants, and women not on antidepressants.

We are climbing... Jacob's ladder...

Mrs. Bremner’s comment is that sudden cardiac events is fairly rare in otherwise healthy women, and antidepressants did not increase the risk of other cardiac events that are more common, like heart attack and stroke. Nevertheless she thinks it is worth paying attention to.

More reactions to this study here and here.

In other words, about half the time someone is writing something and everyone else is supposed to go along. This is actually how medical education works; you see the professor prescribe in a certain way, and you do the same. Given the fact that the pharmaceutical industry has moved in and gotten control of leaders in their fields, through payments for consulting and lecturing, whom they derisively refer to as “KOLs” (Key Opinion Leaders), and whom pay consulting groups to “manage their KOLs”, you shouldn’t have much confidence in these guidelines, as I wrote about recently in “How Much You Gonna Pay Me for Those Guidelines.”

Dr Curt Furberg testifies before Congress regarding expert consensus guidelines

Hey! I think I came up with a better use for those guidelines!

A better use for expert consensus guidelines