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Gambling Man

March 31, 2016

My thanks to Dr. John Mandrola of  theheart.org/Medscape Cardiology for the idea for this post.  Dr. Mandrola is an interventional cardiologist but I forgive him for that because he also reads the fine print and dares to question the status quo, particularly when it comes to preventive medicine.

An interesting paper came out this month in the on-line medical journal Open Heart (a branch of the British Medical Journal) about one particular area of prevention – heart attack.  The researchers used data from a class of cholesterol drugs called statins, such as Lipitor, which have been shown to have a significant benefit in preventing ischemic heart disease (the study cites evidence that statins can decrease cardiovascular death by 20-30%, a number in some dispute).  You can find the whole thing here: http://openheart.bmj.com/content/3/1/e000343.full#aff-1.

The researchers crunched a bunch of numbers and talked to a bunch of people, and these were the results, in part:

  1. 50 year old smoker with high blood pressure and high cholesterol could have his life extended by up to two years by taking a statin.
  2. An healthy 50 year old who starts preventive treatment with a statin at 50 can see a lifespan gain of a mean of 7 months.
  3. BUT, of 100 of those healthy 50 year old men, 93 will see no life extending benefit at all. The other 7 gain a mean of 99 months.  99 months!
  4. Starting statins later than 50 does not increase the life extending benefit.  Quite the opposite.
  5. Of those healthy 100 50-year-olds, there is no way to tell which ones will be in the group of 7.

But here’s the most interesting part of the study – The researchers went down to the Underground (it’s a UK study) and asked around 400 people a simple question:  “Which would you choose – to take a medication that would guarantee you one extra year of life or to take a medication that gives you a 2% chance of living an extra 10 years?”  Then they extended the question – “How about if the medication gave you a 10% chance of living an extra 10 years?” and so on up to a 50% chance.  As you might expect, as the percent chance of getting the 10 years went up, more people chose the chance option.  But, there was always a significant percentage of people who never took the chance option.

So in a certain sense, taking a primary preventive medication, in this case a statin, is a game of chance.  Do you choose to take the medication in the hope you are one of the 7 or do you opt out based on the probability that you’re not?  How much risk are you willing to assume, all other things being equal?  The answers to these questions varies greatly among individuals.

Of course, there are many other factors that go into the decision to start a medication to prevent an illness you might or might not ever get.  There are considerations about side effects, cost, life-style, quality of life, etc.  However, all or most of those considerations are also subject to probabilities and subjective preferences.  Plus, you could die of something besides heart disease that you didn’t take a drug to prevent (or maybe you did but we all have to die of something and sometimes bad stuff just happens.) The take-home is that medicine is not an exact science and every person is different.  What is an acceptable risk for one is an unacceptable gamble for another.  Here’s what Dr. Mandrola says:

The point of this work is that it brings statistics, probability, and cognitive psychology to the doctor-patient relationship. When it comes to treating people with risk factors, not diseases, embracing uncertainty has always been important. But, now, as technology increasingly measures the human condition and creates more risk factors, comfort with gambling in medical decisions has never been more vital.

 

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4 Comments
  1. Mike permalink

    I don’t think the study showed this.

    After reading the paper it looks like they started by consulted life tables and found the annual probability of a heart attack for those with various factors (blood pressure, cholesterol, etc). For each cohort sharing risk factors they determined the probability of death by age due to heart attacks (call it H) and all other causes (call it non-H).

    Then it seems (the appendix with the details is not online even though they say it is) they made assumption that the drugs prevent the same 30% of heart attacks in various cohorts no matter their starting risk. That may be false; maybe there are some people in lower risk groups that have heart attacks just due to causes such as cardiomyopathy and the statins have absolutely no effect on this cohort.

    They further seem to have assumed that the benefit of statins is 30% every year they are taken. This has never been shown in real-world studies; typically they follow participants for 5-10 years. Yet in their simulations they acted as if the benefit would never fade (or increase, to be fair).

    Another assumption seems to be that if you didn’t have a heart attack nothing else took its place to kill you; from the life tables they knew how many in a cohort died from heart attacks, but they do not mention adjusting the non-H death causes upward for the cohort even as they lowered the rate H in the treated group. Statins have been associated in some studies with raising the risk of diseases like diabetes. And even ignoring statin harm, deaths from heart attacks masks comorbidity from the record yet they did not adjust for this.

    With all this they could run simulations using the sum of the H & non-H values by year for the cohort without treatment, and the adjusted H plus the non-H values for the treated cohort. At this point the shape of the life-table graph gives them the results they want. It is relatively flat until the late 60’s or so, meaning that every heart attack they “predict” is avoided by their simulation adds many months life to the person escaping.

    But is it really true? Look at all the assumptions they made, and its hard to conclude they really showed anything about what real patients will experience in the real world.

  2. Exactly! It is so difficult to explain this to my patients, many who expect me to give them a direct answer, concrete guidance. The whole case- based informed decision making thing is hard for many to understand. “Just tell me what you would do if you were me, doc!”

  3. Roger permalink

    The whole pharmaceutical industry has so fraudulently spun the study numbers for so long that it’s hard to take any of this seriously any more. Stating things like “provides a 50% reduction in risk of an MI event” sounds impressive until you look at raw numbers, like the risk reduction goes from 2 in 100 to 1 in 100. Statistically an accurate statement, but a practically negligible real world outcome difference.

    When you factor in all of the miserable side effects statins cause (many unreported), overall, in my opinion, they are not worth it.

    Remember, at an elemental cellular level, cholesterol is absolutely required for proper functioning and overall health. The brain is especially vulnerable to cholesterol tinkering.

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