Science denies your pain

In my Apr. 23, 2016 blog I wrote about Statins & Muscle Pain and described how the drug industry tries to cover up the muscle pain side effects of statins. In June 2017 The Lancet published “Statin-associated muscle symptoms: beware of the nocebo effect.” This is a study that actually denies that statins have side effects and “scientifically proves” that it’s all in the patient’s head! They reference the Nocebo effect, which is the opposite of the Placebo affect. It’s the most condescending attitude toward patients that I’ve witnessed in recent years.

The article was funded by a manufacturer of atorvastatin and reanalyzed data from a previous study (Lancet 2003; 361:1149). The preamble to the article admits that “patient-reported statin intolerance, predominantly due to statin-associated muscle symptoms (SMS) is a common and difficult-to-manage condition affecting millions of patients worldwide.” It is reported in about one fifth of patients. We don’t know how many patients just put up with the side effects and don’t complain. The researchers hired by the makers of the statin drugs say that “the development of SMS does not necessarily signify statin intolerance since statin therapy might not always be pharmacologically involved.”

Drug trials are strange beasts in or of themselves. What about the Hawthorne Effect (AKA the observer effect) in which individuals modify an aspect of their behavior in response to their awareness of being observed. We take that effect and divide humans into two camps – those who like to complain and those who don’t. Couldn’t the Hawthorne Effect explain the results of this study? To me this effect, and the fact that studies are manipulated to get the results that drug companies want, make them almost useless.

Another Lancet study, Mar. 18, 2017 called Safety and Efficacy of Statins describes how the actual occurrence of muscle pain in patients on statins is derived. They subtract the number of patients who report pain on the placebo from patients who report pain on the statins! Does that make any sense at all?

Add to this murky soup a paper in Expert Rev Clin Pharmacol March 2015 called “How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease.”

Here is the abstract of this 2015 paper:

We have provided a critical assessment of research on the reduction of cholesterol levels by statin treatment to reduce cardiovascular disease. Our opinion is that although statins are effective at reducing cholesterol levels, they have failed to substantially improve cardiovascular outcomes. We have described the deceptive approach statin advocates have deployed to create the appearance that cholesterol reduction results in an impressive reduction in cardiovascular disease outcomes through their use of a statistical tool called relative risk reduction (RRR), a method which amplifies the trivial beneficial effects of statins. We have also described how the directors of the clinical trials have succeeded in minimizing the significance of the numerous adverse effects of statin treatment.

In spite of the facts in the above abstract, the pro-statin camp thinks statins are so wonderful that we should just put them in our drinking water and not tell anyone about the potential dangers because then people will just imagine they are having side effects! For the anti-statin view, I tell people to read an insightful and witty critique of the statin industry in Dr. Malcolm Kendrick’s book, The Great Cholesterol Con.

In my blog Cholesterol is Not Your Enemy I remind readers that doctors “want to blame heart disease on something and cholesterol does seem convenient.” To try and convince patients that cholesterol is bad, when it’s not, is one thing. But when they are forced to take a drug that has side effects and they are told that any side effects are all in their heads, that’s Draconian.

What do I recommend? Magnesium of course. For years I’ve talked about one of the functions of magnesium – its ability to lower cholesterol. Here is an edited abstract from the J.Am.Coll.Nutr. 2004 Oct;23(5):501S-505S, by Rosanoff and Seelig:

Mg(2+)-ATP is the controlling factor for the rate-limiting enzyme in cholesterol biosynthesis. Formation of cholesterol in blood, as well as of cholesterol required in hormone synthesis, and membrane maintenance, is achieved in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The enzyme that deactivates HMG-CoA Reductase requires Mg, making Mg a Reductase controller rather than inhibitor. Mg is also necessary for the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C and triglyceride levels and raises HDL-C levels. Desaturase is another Mg-dependent enzyme involved in lipid metabolism. Desaturase catalyzes the first step in conversion of essential fatty acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins, important in cardiovascular and overall health.

Carolyn Dean MD ND

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An Internet Cult?

Steve Nissen recently wrote an eloquent article which accuses statin deniers of  being  an “internet–driven cult with deadly consequences.”  Nissen has done extremely important research helping us better understand atherosclerosis  and is known for being a patient advocate: calling out drug companies when they are promoting unsafe drugs.

I have immense respect for his honesty, lack of bias, and his courage to be outspoken .  He writes:

“Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search en- gine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled “The Grave Dangers of Statin Drugs—and the Surprising Benefits of Cholesterol”. We are losing the battle for the hearts and minds of our patients to Web sites de- veloped by people with little or no scientific expertise, who often pedal “natural” or “drug-free” remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity— or even worse, dementia.”

He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.

The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:

“The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administra-tion. The bill’s principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies.”

Dealing With Statin Side Effects In My Practice

When a patient tells me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I’ve concluded that in any individual patient, it is possible for any drug to cause  side effects.  And, chances are that if we don’t address the side effects the patient won’t take the medication.

If the side effect is significant I will generally tell the patient to stop the statin and report to me how they feel after two to four weeks.

If there is no improvement I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.

If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn’t prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.

At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or livalo.)  If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.

For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long term therapy.

Today a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I’m sure there is a forum somewhere on the internet where patients have reported this). Fortunately he accepted my expert opinion and will continue taking the drug.

If the symptoms persist and the patient continue to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.

Since statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold  for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denials cult thus minimizing the nocebo effect

Antinocebonically Yours

-ACP

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