Why don’t the ‘excellent’ benefits of statins seen in clinical trials appear to transfer to the population at large?

One claim that is often made about cholesterol-reducing ‘statin’ drugs is their ability to reduce cardiovascular events (essentially heart attacks and strokes) by a third. This is a reference to studies in which individuals have been treated with a, say, a statin or a placebo (randomised controlled trials). Saying that a drug reduces risk of cardiovascular disease by a third is relatively meaningless, though, because it needs to be taken in the context of overall risk.

Imagine, for a moment, that 100 people are followed for a length of time and during that time 3 have a cardiovascular event. With statins, maybe 2 would have such an event. So, while the incidence of cardiovascular events has fallen by a third, the real reduction has been just 1 per cent. In other words, quoting a ‘third reduction in risk’ can give us a very inflated idea about the overall effectiveness of statins.

Another way to gauging the effectiveness of statins is to look at relationship between the numbers of statin prescriptions being written and rates of cardiovascular disease. In many parts of the world, statin use has increased considerably. Have we seen declines in cardiovascular disease that mirror this increase in statin use?

I was interested to read a recent study, where researchers assessed the relationship between statin prescription rates and rates of heart disease across Sweden [1]. According to this research, statin prescriptions increased about 300 per cent from 2008 and 2012. Yet, heart attack rates remained essentially the same.

The authors write: “The hypothesis was that a big increase in statin utilisation could be related to a decrease in [heart attack] mortality two years later… However, we found no connection between the change in statin utilisation and change in [heart attack] mortality two years later.”

The authors seem somewhat surprised by their findings and state: “The benefits shown in clinical trials could not be recognised despite that a high fraction of the population studied used statins.”

However, in the paper, the authors discuss findings from other research which makes their own finding quite predictable, I think. For example, the authors quote data regarding the numbers of individuals needed to be treated with a statin over the course of one year to prevent, say, one heart attack. This number, according to the authors, is 235 for men. So, over two years, the number would be about 120. What this means is that over two years, less than 1 per cent of men will be spared a heart attack, but more than 99 per cent will not benefit.

The authors also state that in women without a history of cardiovascular disease, statins have not been shown to reduce the risk of non-fatal heart attacks or death due to heart attack or stroke (cardiovascular death).

Bearing these findings mind, would one expect to see rising statin prescription rates leading to significant falls in rates of heart attacks? I think the answer is no.

In the abstract of their paper the authors refer to the “excellent preventive effect” of statins seen in clinical trials and seem perplexed that these do not appear to translate to benefits within the population they studied. In reality though, statins do not have an “excellent preventive effect” at all – hardly anyone that takes them stands to benefit.


1. Nilsson S, et al. No connection between the level of exposition to statins in the populations and the incidence/mortality of acute myocardial infarction: An ecological study based on Sweden’s municipalities. Journal of Negative Results in Biomedicine 2011;10:6

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6 Responses to Why don’t the ‘excellent’ benefits of statins seen in clinical trials appear to transfer to the population at large?

  1. Robert Park 4 October 2013 at 11:21 am #

    Statistics; okay; this past year the murder rate in the locality where I reside rose considerably in relation to the past 10 years. There was one woman who killed her husband in the past 12 months. The statistical rise makes it sound as if this neck-of-the-woods is a dangerous place in which to live.

    I read some years ago about a State in America (cannot recall which one; could be California) where all prisons were closed yet the crime rate during this period did not rise.

    It is understood that on about four occasions surgeons around the world went on strike during which time the local undertakers nearly went out of business.

    Then it is said that there are more deaths in hospitals due to accident or mistake than there are deaths on the highways from road accidents. The take home message here is that whatever ails you then go for a long walk along the middle lane of the motorway; while this might not bring into effect a cure it sure will increase one’s chances of survival!

    …And one could continue.

  2. paulc 4 October 2013 at 1:19 pm #

    The “Number Needed To Treat” in order to prevent one death is what should really be getting used here, but of course, we know that the number needed to treat to prevent one death from a cardiac event for Statins is ridiculously high… so we aren’t going to see that being bandied about in their papers…

  3. Jake 4 October 2013 at 2:44 pm #

    I just read a study that if I started taking a statin, my absolute risk for a heart event would go down by .2 percent. That is the tiny risk reduction for men over 70 which I am.

  4. Jerome Burne 4 October 2013 at 3:54 pm #

    Another consideration is that clinical trials are specialised situations where the subjects are carefully selected and are usually younger and fitter than the people who are going to be getting the drugs in the real world and unlike the target population only have heart disease or a risk of it. Those who get the drugs are likely to have two or three other disorders and be taking four or five other drugs or more.

    Combine the results from this very unrepresentative population with fact that they will be under much more eagle-eyed doctors and nurses making sure they keep taking the tablets and that they will have had more care in their diagnosis and it is no wonder that the drugs perform even less effectively in the real world than in the trials. I

    n fact one study I saw that looked at this – unsurprisingly it is not a very popular research topic – suggested that in terms of value for money treatments were about 1/5th as cost effective in the real world as in the trials (don’t have reference to hand).Statins’ performance if divided by 5 would certainly not show up in clinical results.

    Given all this it is worth remembering that it is the results from the trials that are then used to by NICE to calculate cost effectiveness and also as a source of information about the risk of side effects.

  5. robert 5 October 2013 at 2:16 pm #

    Putting the NNTT into perspective with a more common item of daily use: dish-washing liquid.

    Nobody would even consider buying it, if only 1 out of 235 plates got clean.

  6. Mike Wroe 6 October 2013 at 9:12 am #

    A very illuminating article in Open Journal of Endocrine and Metabolic Diseases, 2013, 3,, 179-185 is worthy of our close attention and I quote from Professor Sherif Sultan’s conclusion:

    “Primary prevention clinical results provoke the possibility of not only the lack of primary cardiovascular protection by statin therapy but highlight the very real possibility of augmented cardiovascualr risk in women, patients with Diabetes Mellitus and the young. Statins are associated with triple the risk of coronary artery and aortic calcification. These findings on statin major adverse effects had been under-reported and the way in which they withheld from the public, and even concealed, is a scientific farce.”

    On a more positive note, in an earlier article Professor Sultan states “Scientific research on “cardiovascular free” centenarians delineated that low sugar and low insulin are consistent findings. Those who can decelerate the rapidity of this process are prompting their cardiovascular regeneration”. There is hope for us all yet!

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