Statins

Beta-blockers, Statins, AF, and the Nocebo Effect

May 2, 2017 By Dr John

Our brains can easily fool us.

No experienced doctor would deny the power of the placebo effect.

Today I want to discuss the nocebo effect, which occurs when negative expectations of something causes it to have a more negative effect than it otherwise would.

Drugs can exert a strong nocebo effect. If your brain thinks you will have a side effect, you may actually get that effect.

Nocebo brain trickery is relevant to statins. That’s why I used this wording in my last post: (Note the italics)

The actual frequency of muscle symptoms is hotly debated. Randomized controlled trials (in which patients donâ€™t know whether they are taking the statin or placebo) report very small increases in muscle complaintsâ€”about a 1-2% increase. Observational studies, however, reveal higher rates of statin muscle complaints–in the range of 10-20%.

The nocebo effect is also relevant to beta-blockers.

Beta-blockers, which are drugs that blunt the effect of adrenaline, carry enormous baggage about side effects. People think they will gain weight, be fatigued, or get short-winded when taking these drugs. Men think they will become impotent.

The evidence, however, does not support these perceptions. Similar to muscle complaints and statins, our brains may be tricking us.

An elegant study from a famous group of British researchers strongly suggests that most side effects from beta-blockers stem from the nocebo effect.

The authors did a systematic review of blinded trials that used beta-blockers in patients with congestive heart failure–a common reason to give beta-blockers. (The linked review is open access.)

They found, sit down for this, 28 of 33 classically described side-effects are not more common on beta-blockers than placebo. Table 3 and Figure 2 of the paper are eye-openers.

Side effects, such as, headache, impotence, weight gain, low blood pressure, shortness of breath were no more common with beta-blockers than placebo.

In fact, the side effect of depression, often attributed to beta-blockers, occurred less often in patients who took the real drug. Read that sentence again.

Some side effects were more common on beta-blockers. Dizziness, for example, occurred 3.7% more often in the beta-blocker arm. But the authors explain that a 3.7% increase actually means that of 100 patients who get dizzy on the beta-blocker, 81 of them would have had it on placebo.

The nocebo effect can also turn asymptomatic people with atrial fibrillation into symptomatic people with atrial fibrillation. I’ve seen the scenario many times. Here’s how it goes:

Mr Smith is in for routine follow-up. I note before going in the exam room that his ECG shows AF. Last year he was in sinus rhythm.

“How are you, Mr Smith?”

“I feel great.” I ask again…”Great? That’s a strong word.”

“Yea, doc, I have never felt better.” His wife confirms that he is active and vigorous.

But then the cheery confident demeanor turns sour when I tell him his ECG shows AF.

I spend the rest of the visit reassuring him that it doesn’t matter; he’s on anticoagulant already, his heart rate is controlled, the previous echo is normal.

No matter, weeks later, Mr. Smith is calling because he is fatigued and short-winded. And so begins the balance of treating AF symptoms without causing harm.

***

The authors of the beta-blocker side-effect paper boldly concluded that “clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect…”

I wonder. We clinicians have immense power with our words. I can’t quantify it, but the human brain surely controls a lot of our health.

JMM

P.S. I’ve written about the possible placebo/nocebo effect of AF ablation. Click on the link: Could Ablation for AF Be an Elaborate Placebo?

Statins, Like All Medicines, Are Neither Good Nor Bad

April 30, 2017 By Dr John

We have to talk about drugs.

No, not illicit drugs, but medications used by doctors and patients.

Plaintiff attorneys run ads on TV that fool people into thinking certain meds are bad. The current one I deal with is the clot-blocking drug rivaroxaban (Xarelto.) Before that, it was dabigatran (Pradaxa). If, or when, the makers of rivaroxaban settle a class action suit, you can bet apixaban (Eliquis) will be next.

These ads are a problem because they use fear persuasion (see Scott Adamsâ€™ blog), and because they can induce patients to stop taking or not start a beneficial medicine.

Lots of other medications suffer from a â€œbadâ€ or â€œtoxicâ€ branding. Some people think statins are bad; many people think amiodarone is toxic. Warfarin (Coumadin) still suffers from the branding of rat poison.

I want to be clear: medications are neither bad nor good. Medications are chemicals that act on cells in the body in an attempt to create benefit. All medications can be toxic.

Toxicity turns mostly on dose. (Chance can also play a role in toxicity.)

Warfarin kills rats because the rodents keep eating the pellets and the drug builds up to high doses. In humans, we adjust the dose.

When patients tell me certain medications are toxic, I remind them that too much water, taken by endurance athletes, can cause dangerously low sodium levels that may lead to seizures. Oxygen given at high doses for too long in patients on ventilators can damage the lungs. Life saving-antibiotics can cause life-threatening colon infections.

I would urge doctors and patients to frame medications with the big four questions:

Four Crucial Qustions

As an exercise, letâ€™s apply the four questions to the statin drugs (we exclude from this discussion people with familial hypercholesterolemia):

What are the benefits of taking statins?

There is only one benefit of statins: to reduce the future probability of a heart attack, stroke or death. Do not make the mistake of thinking statins are for cholesterol lowering. The drugs do lower cholesterol levels, but thatâ€™s a mere blood test. There are plenty of drugs that lower cholesterol but do not reduce the risk of heart attack or stroke.

The benefit of statins, therefore, is a probabilistic one. Itâ€™s like a lottery. You take the pill every day in hopes it will prevent a serious cardiac event in the future.

Numerous randomized controlled clinical trials (the highest level medical evidence) confirm that statins do reduce the probability of a cardiac event.

In absolute terms, the degree of statin benefit depends on whether a person has had a cardiac event.

For those without a previous heart attack, stent, bypass or stroke, statin benefits are smallâ€”no mortality benefit and about a 1% reduction of nonfatal cardiac events over the next 5 years. Doctors call this primary prevention.

For people with a history of a cardiac event or stroke due to a blockage of some sort, statin benefits are greaterâ€”about a 1.2% lower risk of dying and 2.5-3% lower risk of a non-fatal heart attack over the next 5 years. Doctors call this secondary prevention.

What are the harms of statins?

The best known harm of statins are muscle issues. I use the word issues rather than damage because true muscle damage is rareâ€”about 5 in 10,000.

The actual frequency of muscle symptoms is hotly debated. Randomized controlled trials (in which patients donâ€™t know whether they are taking the statin or placebo) report very small increases in muscle complaintsâ€”about a 1-2% increase. Observational studies, however, reveal higher rates of statin muscle complaintsâ€”in the range of 10-20%.

The second potential harm of statins is a small increase in diabetes. One of the smartest doctors on the Internet, Dr. Richard Lehman, says “the issue of [statin] induced type 2 diabetes is just an artifact of the way we define the threshold for T2DM. Statins often cause a small rise in blood sugar, which would only be of significance if it was associated with an increase in macrovascular or microvascular disease. On the contrary, statins reduce macrovascular disease end-points, and there is no evidence to suggest that they increase eye or kidney microvascular disease (which are very rare in the glucose range we are talking about).â€

A third potential harm of statins is the burden of taking a pill every day. Scientists call this pill â€œdisutilityâ€ and its measured in how much extension of life one would trade for taking a pill every day. People have different feelings about pill burden.

Another possible (emphasis here on possible) harm of statins is that the drugs may interact in a negative way with lifestyle. In a 2014 theheart.org | Medscape Cardiology column that went a bit viral (647 comments), I cited two observational studies, one that reported a higher calorie intake of statin users and the other less physical activity in male statin users.

Are there simpler safer options?

Opinion alert here: I strongly suspect that a healthy lifestyle delivers similar benefits.

Eating modest amounts of real food, not processed food in packages, doing regular exercise and managing stress would likely deliver lots of probabilistic benefits for reducing the odds of having heart disease.

This â€œinterventionâ€ however, has not been compared to statins in randomized controlled trials. Cardiologists Aseem Malhotra, Rita Redberg and Pascal Meier, writing in the British Journal of Sports Medicine, point to the obvious reason for this: â€œThere is no business model or market to help spread this simple yet powerful intervention.â€

What happens if I do nothing?

The most likely outcome of not taking statins is the same as if you take oneâ€”nothing. In the best case, that of secondary prevention, the risk reduction for nonfatal cardiac events is about 2.5-3%. That means one has to treat about 39 patients for five years to prevent one event. The odds are you would be in the 38 of 39 category, but you donâ€™t know.

Doctors think this is a good trade. If these stats are applied to populations, many heart attacks can be prevented.

The ultimate decision is up to you. You are not a population.

JMM

You can do this exercise for any medical intervention or medication. Why we don’t do it more often is hard for me to understand.

Four Crucial Questions To Ask Your Doctor

April 17, 2017 By Dr John

I am seeing an increasing number of patients who did not know they had a choice about taking a medicine or having a procedure.

Why did you have that heart cath? A: My doctor said I should.
Why are you on that medicine? A: My doctor prescribed it.

It’s time we re-review the basic four questions you should ask your doctor.

I wrote about this in April of 2015 for WebMD. Here is 2017 update:

1. What are the odds this test/medicine will benefit me?

Medical decisions are like gambles. Benefit is not guaranteed. In my field, catheter ablation of supraventricular tachycardia (SVT) has a success rate approaching 99%, but the success rate for ablation of atrial fibrillation or ventricular tachycardia is much lower.

Another aspect of discussing benefit is defining what is meant by benefit.

Statin drugs, for instance, are quite good at lowering cholesterol levels, especially LDL, the bad cholesterol. But LDL is what we call a surrogate marker. Having a lower LDL is supposed to deliver future benefit–say a lower chance of a heart attack, stroke or death.

If you don’t have heart disease, just a high cholesterol level, your future benefit of taking a statin is small. Abramson and colleagues, writing in The BMJ, estimated the average future benefit of statins in low-risk patients to be in the range of a 7 in a 1000 risk reduction of a non-fatal event over the next five years. That means that about 140 patients have to take a daily statin to prevent a heart attack or stroke in one patient. Is that small but statistically significant benefit worth taking a statin? That’s up to you–not your doctor. (Note: the risk reduction with statins is higher if you have established heart disease.)

Another example in the news lately is the benefit of PSA screening for prostate cancer. The USPSTF, a major governmental guideline committee, recently changed the recommendation for PSA screening in younger men from a D to a C. In one sentence, the benefit of PSA screening is that it reduces your risk of dying from metastatic prostate cancer by about 1 in a 1000, but that small risk reduction does not translate into a survival advantage overall. (See oncologist Dr. Vinay Prasad’s review here.)

2. What are the downsides or harms of the test/medicine?

No intervention in the practice of medicine is free. Here I don’t mean costs, I mean harms. You can’t have an ablation without incurring the risk of procedural harm; no doctor is perfect. You can’t take a drug without exposing yourself to the potential toxicities of the drug. (Even antibiotics come with the risk of severe allergy or secondary infection with Clostridium difficile colitis.) This is where you need your doctor to help balance the probability of harm versus the probability of benefit.

An important warning though: Doctors under-estimate harms and over-estimate benefits. I recently wrote about a systematic review from two Australian researchers which showed clinicians rarely had accurate expectations of benefits or harms, with inaccuracies in both directions.(1) This group has also found patients, too, over-estimate benefit and under-estimate harms.(2)

3. Are the simpler safer alternative options?

When I explain options to patients, I always tell them there are alternatives. An alternative to catheter ablation is an attempt to control the rapid heart beat with a medication. In heart disease prevention or treatment, one of the most common alternative therapies is an improved lifestyle. For instance, the alternative to taking a statin drug for cholesterol or a blood pressure drug for hypertension, is a better diet, weight loss and more exercise.

4. What happens if I do nothing?

As mainstream medicine increasingly medicalizes much of the human condition, this last question grows in importance.

The famous French philosopher Voltaire said that the art of medicine consists in amusing the patient while nature cures the disease. Time is an underused tool in the treatment of illness. Despite our dominance as a species, patients and doctors underestimate the ability of the human body to heal itself. The main advantage of watchful waiting is that it allows patients to avoid harm from healthcare.

Another aspect of not taking a drug or not having a procedure is living with the condition. This comes up a lot in atrial fibrillation care. Sometimes, often even, the presence of atrial fibrillation episodes does not diminish the quality of life enough to warrant taking the risks of treatment–say drugs or procedures. It’s a very similar story in surgery: maybe the hernia or inflamed joint bother you, but not enough to have the surgery.

JMM

References:

Hoffmann TC, Del Mar C. Cliniciansâ€™ expectations of the benefits and harms of treatments, screening, and tests: A systematic review. JAMA Internal Medicine. 2017.
Hoffmann TC, Del Mar C. Patients’ expectations of the benefits and harms of treatments, screening, and tests: a systematic review. JAMA Intern Med. 2015;175:274-286

More on the gambling decision to take statins

March 31, 2016 By Dr John

In my last post, I wrote my initial thoughts of an important new study on how the decision to take a medication or have a screening test in the name of prevention is similar to playing the lottery.

I promised to think and write about the study more carefully. My latest thoughts are now published over atÂ theheart.org|Medscape Cardiology.

Here is the intro:

Medicine is easier when people are sick. In treating heart attack or stroke, certainty rules over uncertainty. The best outcome of a heart attack or stroke, however, is not to have had one.

Prevention is where medicine gets hard, very hard. To prevent something that may or may not happen in the future, we operate with probabilities. Preventive medicine also requires us to treat people who are not sick. Given our oath to first, do no harm, that gets tricky.

Current thinking on primary prevention involves applying results from clinical trials to individuals in your exam room. We say taking this drug or having this cancer screening test will reduce your future risk of dying from that disease by x% or y%. But people don’t care about population averages; they want to know their odds of benefit and how much benefit to expect.

A new study,[1] published in Open Heart , provides a novel way to think and discuss these odds. I will try to convince you that this paper may be one of the most important medical studies of recent times.

To read more, click the title of the piece: Primary Prevention: What Medicine Can Learn From Monte Carlo

JMM

Remember, you need to register with Medscape with an email. It’s free.

A new way to discuss statin drugs

March 21, 2016 By Dr John

A new study published last week in an open heart journal changes the conversation about how patients and doctors think about and discuss preventive therapies–such as statins.

Dr. Richard Lehman may be the smartest doctor on Twitter. This is what he said:

This is a game-changer https://t.co/WgGdLlodbL

— Richard Lehman (@RichardLehman1) March 20, 2016

Most discussions about using statin drugs focus on a 5-10 year period. That’s not the right way to discuss these drugs. When we take a statin drug (or screen for cancer, or any other preventive intervention) we do it to live longer–not just 5-10 years.

Here is a link to the (free) study. The editorial is here.

Researchers from the UK used national registries to calculate death rates. They then devised a mathematical model to calculate the probability distribution of lifespan gains from statin interventions. They used the well-accepted relative (CV) benefits of statins of 20-30%. In the third part of the study, they surveyed random people in train stations, asking how they would judge potential benefit from the drugs.

Before I tell you the results, let’s consider how we currently explain statin benefits. In primary prevention, the absolute benefit from a statin drug (or cancer screening) is small. How small is a matter of debate, but what opponents to these therapies rightly say is that most people who take these drugs get no benefit. (If the NNT is 50, 49 get no benefit.)

The problem with that strategy is we use average estimates of benefit and translate them to everyone who would take a statin. You know that is not how life works. You could start on a statin, and come down with cancer, or get hit by a bus, or die from pneumonia the next year. Then the protective effects of statins never helped you.

The researchers sought to figure out the probability that statins (or any other prevention strategies) would help you over a lifetime. They used what’s called a Monte Carlo simulation. The model gives a range of probabilities for life-expectancy gains for each individual on primary prevention. “MCS is like throwing multiple dices at the same time â€“ it is astrology with a dice.” The Monte Carlo simulation is explained well in this blog post. (Credit to Dr. Saurabh Jha, @roguerad on Twitter.)

The findings of this study changes everything.

Lifespan gains are concentrated within an unpredictable minority. For example, men aged 50â€…years with national average cardiovascular risk have mean lifespan gain of 7â€…months. However, 93% of these identical individuals gain no lifespan, while the remaining 7% gain a mean of 99â€…months. See Figure to the right> Screen Shot 2016-03-20 at 8.14.46 AM

Another finding was that younger people benefit more from statins. That’s because, even though they are lower risk, they have longer to accumulate gains. Likewise, an older person has a higher risk of death from a heart attack, and in the old way of thinking, would benefit more from statins. This new model, however, predicts that an older person’s benefit would be lower because of competing causes of death.

Here is a nice quote from the editorial:

The study highlights the problem of focusing on disease-specific mortality rather than total mortality in the evidence used to recommend various medical interventions. The two measures are taken as similar but they do not necessarily follow each other as well as researchers would sometimes like to think.

The third finding from the study was that when people were asked what they preferred, they chose the lottery approach to lifespan gains. “Our survey illustrates that people often prefer a small chance of a large benefit over the certainty of a small benefit, even when the mathematical average gain from the former is smaller.”

This is my first crack at translating this important study. I learned of it this weekend. This changes the way we will talk with patients, and among other doctors.

Look at that graph: 93% of this group gets no benefit but the 7% gets tremendous benefit. It’s like a lottery to see if you will be the one who benefits.

One important weakness of this model, which was discussed in the paper, is that it only counts benefits of intervention. Statin drugs and cancer screening clearly have possible harms.

Stay tuned.

JMM

Medical evidence — Don’t get fooled again

October 4, 2015 By Dr John

I’ve never been more convinced that the ease with which knowledge is shared in the digital age is a force for good.

I loved the video below. These two guys read conclusions of medical studies for humor. That’s a good one.

James McCormack is a pharmacist, professor, medication mythbuster, and healthy skeptic at the Faculty of Pharmaceutical Sciences at UBC. He’s on Twitter at @medmyths. Dr G Michael Allen is an Associate Professor in Family Medicine at the University of Alberta.

It’s 50-minutes; but if you don’t want to be fooled by the newest evidence, or if you are drawn to the beauty of common sense, it’s well worth your time. Plus the music.

JMM

Update: Baltimore, Safety in AF ablation, Podcasts, and some personal notes

May 4, 2015 By Dr John

On Baltimore:

Human beings rioting in the streets of an American city forced cancellation of an important cardiology meeting. This is a vivid example that doctors do not practice in a vacuum. We are connected to this world. Here in Louisville, just a few miles north, an HIV crisis runs amok because of IV drug use. Despair. Inequality. These are no small things. What bothers me most about our healthcare system is the waste. We burn money. If we stopped doing that, we would have more to do for the less fortunate. I make a call out to every day physicians to stop burning money. Medicine Can’t Ignore Baltimore and Ferguson.

On a failure of a safety method in AF ablation:

The most devastating complication of AF ablation is damage to the esophagus. Thermal lesions can lead to a connection (a fistula) between the esophagus and the left atrium. This–thankfully rare–event leads to death in the great majority of people. Most doctors take evasive action to protect the esophagus. One maneuver is to monitor temperature in the esophagus. The idea is that if a burn in the heart causes a rise in temp in the nearby esophagus, the operator stops burning and damage is avoided. Sounds good, right? Except a new study from Germany suggests the act of temperature monitoring associated with dramatic increases in thermal lesions. AF Ablation: Esophageal Monitoring Harmful or Helpful?

Podcast for May 1, 2015:

This 12-minute video podcast includes my comments on Baltimore, outcomes in LVADs, gene-therapy for heart failure, statins for all elders, and an FDA alert on hand sanitizers. May 1 Cardiology News Podcast

Podcast for April 24, 2015:

This 11-minute video podcast includes my comments on a consensus statement from AHA on the treatment of adults with congenital heart disease, safety of sports in youngsters with Long QT syndrome, the vital importance of treating sleep apnea in patients with AF, the cardiovascular risk of divorce, and the Dr. Oz controversy. April 24 Cardiology News Podcast

Mention in the Houston Chronicle:

Markian Hawryluk is an accomplished healthcare journalist who contacted me for my thoughts on the Watchman, a device used to occlude the left atrial appendage in patients with AF. It was a long slog through the FDA process but Watchman finally made it. I am worried about where this chapter in cardiology is headed. You can read my quotes here: New device effective in preventing blood clots, but experts fear overuse, high costs. I will surely have more to say about this focal solution for a systemic problem in the months to come. My stance has changed little since I wrote Eight Reasons to Remain Doubtful on Watchman in 2013.

Personal Note:

I am currently on a Mark Twain kick. My recent reads include, The Handmaid’s Tale (Margaret Atwood), Hitch-22, (Christopher Hitchens’ memoir), The Sun Also Rises (E Hemingway), The Human Stain (Philip Roth), Writing Tools and How to Write Short (Roy Peter Clark).

I am back to running and mountain biking. I like both–for lots of reason. One is that they keep my legs sufficiently tired so that I am less likely to succumb to criterium thoughts. It is that season. And crits are so beautiful.

JMM

Why don’t people ask their doctors more questions?

April 22, 2015 By Dr John

I do not get it. Day in and day out, I ask patients why they take a medicine. Many do not know. “My doctor put me on it,” goes the common response.

Take statin drugs, for example. I often ask a person why they are taking the drug? With rare exception, the person says it is to lower cholesterol.

That’s not the right answer–and herein lies much of the problem with preventative medicine. A statin drug does indeed lower cholesterol but its main purpose is to reduce the risk of heart attack, stroke or death in the future. Cholesterol is just a number. It’s a surrogate that we can measure but it’s surely not the only way statins provide benefit. (There are many drugs that lower cholesterol but do not decrease the risk of heart attacks or death.)

The point here is that almost no patient I have met can quantify the benefit or harm of these common meds. I’ve written before that statin benefit in patients without heart disease is very small and may be countered by its small-but-real adverse effects.

Antibiotics are another example. The human body has an immune system for a reason. We fear infections but we don’t seem to fear antibiotics. Now, most hospitals in the US are struggling with problems related to antibiotic overuse.

A patient gets a seemingly harmless prescription for azithromycin (Z-Pak) for a case of viral bronchitis and weeks later nearly dies of Clostridium Difficile. Did that person know the benefits or harms or alternatives? I doubt it.

You can apply these lessons to almost any therapy used in modern medicine today.

It is in this context that I wrote my latest piece for WebMD. 4 Questions to Ask Your Doctor

JMM

Athletes, AF, Anticoagulants, Statins, Peanuts, and Dishwashers

February 28, 2015 By Dr John

Here is an update on my recent writing.

Athletes and AF:

I was honored to be invited back to the Western AF symposium in Park City, Utah. Last year, I presented on social media. This year, Dr. Nassir Marrouche (University of Utah) asked me to tackle the topic of atrial fibrillation in athletes. This is no small matter.

In the process of putting together the 20-minute talk, I wrote an essay as a guide. In Athletes and AF: Connecting the Lifestyle Dots, I review the evidence, mechanisms, and treatment considerations of the endurance athlete with AF.

My argument in the talk and essay is that AF happens for a reason–even in athletes. We are at an inflection point in the way we think about AF. I made the case that the exercise-AF narrative fits with this new thinking.

AF and anticoagulant drugs:Â

In The Gambling Game: Clot vs Bleeding, I address the issue of preventing stroke in patients with atrial fibrillation. The stimulus for this essay was a new study from Sweden that reported lower than expected stroke risk in non-treated AF patients with only one risk factor. (CHADS-VASC-1).

This is important data because knowing the risk of stroke without treatment informs the decision on whether to take an anticoagulant drug. It is definitively not a yes or no call. The tradeoff is always the same: anticoagulant drugs lower the risk of stroke but increase the risk of bleeding. You need stats (and a good adviser–doctor) to make the best choice. And it is your choice.

Statin drugs:

In the post, Statins in Primary Prevention: Welcome to the Gray Zone, I discuss the issue of predicting the future–at least, as it pertains to cardiovascular events. A recent study suggested that standard CV risk calculators overestimate the chance of a future heart event. That is big news because it affects the controversial decision to use pills to prevent heart disease.

For instance, statin drugs, like any medical or surgical treatment, force a patient and doctor to make a gamble. Does the benefit of the drugâ€”a lower chance of a heart attack or strokeâ€”outweigh the risks and costs of the drug?

Recently, guideline writers suggest statin benefit turns to the good when 10-year risk is greater than 7.5%. My post deals with the problem of knowing your future risk, and the wide swath of gray area in the use of statin drugs for primary prevention.

Peanuts, Fats, Dishwashers and Health Advice:

Being wrong about health topics is like the new normal.

For years, children’s health experts scared parents about peanuts. Don’t let your baby near peanut products until they were three. Now it looks like the opposite is true.

For years, nutritional experts warned us that eating fat would make us fat–and give us heart disease. That, too, looks wrong.

And in recent years, experts have created a systemic phobia of all things dirty. Bacteria and viruses are to be feared. Makers of hand sanitizers have cheered the new aversion. Now we learn that leaving a little bacteria on your dishes and utensils (and eating fermented foods) may help prevent allergies. Simply…you might be too clean.

How is this happening? How can experts have been so wrong about such basic things?

You can read the entire post here: Peanuts and More: When Health Advice Is Wrong

Thanks for reading.

JMM

I hope to post the Athletes and AF PowerPoint soon.

Does the controversy over statin drugs herald a new era of doctoring?

October 19, 2014 By Dr John

In July, I wrote a short blog post expressing doubt about the value of statin drugs. Medscape republished it on their website and it went viral–in a medical sort of way. The post has 631 comments. It was Tweeted extensively, page views have been off the charts (for me), and I even received an invitation to discuss my views on a famous television show, which I declined.

This week, Medscape published Statins: The Good, the Bad, and the Unknown, a referenced review article of my blog post and its comments. In the well-written five pages, Dr. Gordon Sun (UCLA Medical Center) covered four major issues of present-day statin therapy. I’d recommend reading the entire article. Here are a few words about the issues he highlighted.

Statin benefit:

Everyone, including me, agrees that statin drugs confer benefit in patients with established blood vessel disease (atherosclerosis). The doubt I expressed about statins related to their value in three groups of patients–those without blood vessel disease, women and the elderly. In these patients, which number in the millions, the benefit of statin drugs are dubious.

Consider the what-if possibility of statin drugs being available over the counter. Would a consumer (say with an elevated cholesterol level and no other risk factors) part with her own money for a drug that has no mortality benefit and a NNT (Number Needed to Treat) of 140 to prevent a non-fatal heart attack in the future? Might this person spend hundreds of dollars thinking she was the 1 of 140, or, would she justify not buying the drug because she was far more likely to be one of the 139 of 140 who would get no benefit?

Statin myopathy:

In the second page of Dr. Sun’s review article, he delves into the debate on muscle-related complaints with statins. This controversy played out recently in the British Medical Journal. The consternation stems from the fact that observational trials report a much higher incidence (11-29%) of muscle complaints than do clinical trials (1-5%). The most likely explanation is that patients in clinical trials were screened for muscle issues before entering the study, whereas in real life, statin drugs are used in all-comers. In other words, clinical trials may not be representative of real world populations.

Any caregiver that has more than a token practice will tell you that statin drugs cause muscle symptoms in more than 1-5% of patients. What’s more, the biochemistry of statins lend plausibility to muscle complaints. Although cognitive bias can obscure truth, it strains credibility to ascribe statin-induced muscle complaints to the nocebo effect–IMHO.

Statin-lifestyle interaction:

Dr. Sun further expanded on the idea that a “healthy lifestyle is the foundation for cardiovascular health.” This idea is central to how we think about using cardiac drugs or procedures. When I prescribe a treatment to a patient, I explain the goals of the intervention. In the case of statin drugs, the goal is not to move a lab value (LDL or HDL); it is to extend life. With this long-term objective in mind, studies that suggest patients on statin drugs eat more, move less and put on weight should give us pause. We have recently learned, from a Swedish study, that simple lifestyle behaviors may render much of heart disease unnecessary–without drugs.

The interactions of drugs with other drugs and unintended biologic functions is greatly under-appreciated. Nary is the chemical that exerts its effects on only one system. And…as we learn more about personal (genomic) medicine, it will soon be clear how much our genes determine a drug’s effects.

Personal beliefs about statins–and the future of medical practice:

The final issue addressed in Dr. Sun’s review extends past the biology of statin drugs and heart disease. It gets to the notion of how medicine will be practiced in the future. Namely, in this information age, who is the expert?

Dr Sun noted that most of the commenters on Medscape (caregivers) shared my doubt about statin drugs. And it wasn’t just Medscape readers. He cited a survey of more than 1600 New England Journal of Medicine readers, in which more than half would have withheld statin drugs in a case of primary prevention. These are remarkable findings because recent expert guidelines have suggested an expanded role for statins.

At least for statin drugs, the disconnect between patients, doctors and experts is expanding. This, I believe, heralds a new era of medical decision-making. In the past decade, guideline-directed care equated to quality care. You have a disease and we have established treatments. Now, it seems the more we learn, the less we know.

Statin doubt is one example. The lack of benefit of aggressive blood pressure and blood sugar control in the elderly is another. How the drug dronedarone rose to first-line therapy in atrial fibrillation could be taught as a lesson in Conflict of Interest-101. Don’t get me started on the marketing of fear, eg, the LifeVest and the pink campaign. Then there was the idea of giving beta-blockers to patients before surgery–a guideline-directed measure now debunked because of fraudulent science.

I can feel it. Can you? Skepticism is making a comeback–due in large part to the spread of knowledge.

In a world where healthcare increasingly fails to deliver health, this is cause for celebration.

JMM

Growing doubt on statin drugs — the problem of drug-lifestyle interaction

June 16, 2014 By Dr John

My mind is changing about statins. I’m growing increasingly worried about the irrational exuberance over these drugs, especially when used for prevention of heart disease that is yet to happen.

An elderly patient called my office last week to tell me thank you…not for a successful procedure or surgery, but rather, for helping with a problem that had dogged her for a decade. How did an electrophysiologist help a patient without doing a procedure?

I stopped her statin.

A few weeks later, the patient said, her muscle and joint pain were gone. “I thought it was arthritis. I’m walking now. I haven’t felt this good in years. I’ve even lost 5 pounds.”

So why was this elderly patient on a statin?

It was being used to lower cholesterol in the hopes that it would lower the risk of a future heart attack or stroke. This is called primary prevention. The patient had no vascular disease but had a high cholesterol level.

The problem of course is that statins have not been well-studied in elderly women. Her doctor, and the medical establishment writ large, have extrapolated findings of clinical trials on younger mostly male patients to all patients with high cholesterol levels. This is a striking jump to make given that low cholesterol levels in the elderly associate with higher death rates.

Anecdotes are not evidence but this one moved me to review some of the statin evidence. And to think (again) about treating people versus disease.

As always, let’s start with the truth–absolute not relative values. Then I will move on to some new revelations about statins, and then an interesting theory of why potent cholesterol-lowering drugs have such painfully small effects on overall cardiovascular outcomes.

The Truths:

When statins are used in low-risk patients without heart disease (primary prevention) there is no mortality benefit. That’s right. Your chance of dying are the same on or off the drug, regardless of how much the statin lowers the cholesterol level.

When statins are used for primary prevention there is a small lowering of future vascular events (stroke/heart attack) over 5-10 years. The absolute risk reduction is in the range of 7 per 1000. That means you have to treat 140 patients with a statin (for five years) to prevent one event. Or this: for 99.3% of statin-treated patients, there is no benefit. I like to call this the PSR or percent same result.

There is also general agreement that statins increase the risk of developing diabetes, especially in women, and that risk is about the same as preventing a stroke or heart attack, approximately 1%.

Another fact is that patient-level (raw) data from the industry-sponsored cholesterol trials have not been independently analyzed. Systematic reviews from the Cochrane group have analyzed only published data rather than the raw data. There is likely a difference.

There is great debate about the incidence of statin side effects, such as muscle pain, cognitive issues, decreased energy, sexual problems, kidney and liver injury, among others. In the industry-sponsored randomized controlled clinical trials, discontinuation of statins was not significantly different from placebo. Observational data, and the observations of any clinician, provide a different picture.

No statin drug has ever been compared to lifestyle interventions for the prevention of cardiovascular disease.

New Revelations:

A study presented in April 2014 at the Society of General Internal Medicine Meeting in San Diego showed that individuals prescribed statin therapy for high cholesterol consumed more calories and more fat than non-statin users. And, not surprisingly, this increase in calories paralleled an increase in BMI (Body Mass Index) in statin users.

An analysis of a prospective cohort study of menÂ (published in JAMA-IM) revealed that physical-activity levels were “modestly” lower among statin users compared with nonusers independent of other cardiac medications and of medical history.

Possible Connecting Theory: Drug-Lifestyle Interaction

These two recent studies are troublesome. As pointed out in the excellent coverage from heartwire journalist Michael O’Riordan, there may be an interaction between medication and lifestyle. Namely, if statin users consume more calories, gain weight and exercise less it becomes easy to see why cardiovascular benefits are so small.

It’s been really hard to explain why the striking reductions in bad cholesterol (LDL)–up to 30-50%–from statins hasn’t translated into significant future benefit.

One possibility is that cholesterol levels are a lousy surrogate for outcomes. That surely seems true in the elderly, but what about in younger patients and those with familial high cholesterol? These patients are definitely at increased cardio-vascular (CV) risk. So cholesterol levels are surely not unimportant. There is convincing data, for instance, that higher HDL (good cholesterol) levels associate with lower CV risk.

Another possibility for lack of statin benefit is analogous to AF rhythm-control and high blood pressure issues. As in, yes, it’s better to be in regular sinus rhythm and have normal blood pressure, but getting to those goals with pills isn’t the same as being there naturally. With rhythm-control and blood pressure drugs the achievement of the desired outcome is muted by side effects from the drugs. Perhaps it’s the same with statin drugs?

You don’t have to posit malfeasance on the part of big pharma here. All you have to do is think past the disease-specific mindset of modern-day medicine. We are much more than our cholesterol level. A statin drug, like so many drugs which block enzyme pathways far upstream in major cellular pathways, is going to have much more biologic action than just moving an easily measured cholesterol level.

When you step back and look at medications as chemical modifiers of cellular processes in complex biologic systems like our body it’s easy to understand that health comes not from pills. Not even statins.

JMM

References:

Should people at low risk of cardiovascular disease take a statin? BMJ 2013;347:f6123

The above authors reply to criticism: http://www.bmj.com/content/347/bmj.f6123/rr/678736

The Cholesterol Myth | YouTube video of Australian TV investigative journalism piece: http://youtu.be/F0kIC-dbW2g