Statins vs. Exercise: The Real Cholesterol War?

I very much enjoyed a recent article on cholesterol in New Scientist by Michael Brooks, which is based on his personal experiences with statins. I’d recommend the article as a whole, but the point that really grabbed me was the following quote:

 

“After two years on statins I had stopped going to the gym. I gave up running. I cut down on swimming. I simply couldn’t bear the pain – or the humiliation of being so weak and sluggish. In the end, I told my doctor I wanted to stop taking statins because they were turning me into a couch potato. Surely that was as bad for me as having high cholesterol?”

The article explores the very complicated risk/benefit calculations that surround the use of statins. We take lots of these drugs (something over 60 million prescriptions per year in the UK), and they are very effective in preventing heart disease and stroke in the population. However, when we try to predict how much taking a statin will help an individual, things get much more complicated. For example, statins seem to vary in effectiveness depending on whether we use them for either primary or secondary prevention. Statins make a dramatic difference to preventing further heart attacks (and death from heart disease) in people who have already had one (secondary prevention). However, the picture is a bit more equivocal in people who have not had a previous heart attack (primary prevention). Some reviews seem to suggest that, for instance, all-cause mortality doesn’t change in people who take statins for primary prevention – although note that this conclusion is contradicted by the most recent (2013) Cochrane review. The degree of benefit also seems to vary depending on the overall risk of heart disease, as this set of pleasingly complicated slides suggests.

 

Rather than deal with all of these issues here, though, I want to think a little bit about the relationship between statins and exercise. As Brooks’ experience suggests, taking a statin might discourage exercise. For emphasis, note that I’m not endorsing this claim, but simply exploring the issue. We know that muscle pain is a relatively common side-effect of statins. What we don’t know is how commonly that muscle pain prevents exercise. Assuming that Brooks’ experience is fairly common, though, we have a really interesting problem: taking statins a) improves lipid profiles, therefore preventing heart disease but b) prevents exercise, thus causing heart disease. In our 2014 joint paper, we described this kind of set-up as the Masking Problem:

 

“To see the problem, suppose you have very detailed evidence of a mechanism linking A and B. E.g., you have found the bacteria and understood how they cause the disease, you have studied an antibiotic and found that it kills the right bacteria, and doesn’t harm people, and you are confident that killing the bacteria will cause full recovery. So you can trace the mechanism all the way from the antibiotic to recovery, or trace the process, in Steel’s terms (Steel 2008). However, you cannot conclude that taking the antibiotic will cause recovery. This is because finding one mechanism linking A and B does not prove that there are no other mechanisms operating. The human body is a complex system, and the more we discover about it the more it seems that it is very common to have multiple mechanisms operating. If there are multiple mechanisms operating, they may impact on each other, and one or more may mask the effects of the mechanism you have discovered.”

(Clarke, Gillies, Illari, Russo and Williamson 2014: 350-1)

 

I think that it would be worth studying further. I don’t know if there are any analyses that look at the effects of statins and exercise on cardiovascular outcomes jointly in the context of primary prevention, but given the importance of getting the issue right, it would seem worth doing. Perhaps a post-hoc analysis of existing data would be possible? There are certainly a couple of reviews that suggest there is at least some research going on that might explain why statins seem to cause muscle pain (see, for example, Opie 2013 and Parker and Thompson 2012). But, as the first of these authors writes, there are many more questions than answers when it comes to statins and exercise together.

 

“There is, as yet, no clearly defined outcomes based policy to deal with such symptoms from use of either statins or exercise or both.” (Opie 2013)

 

Finally, this fascinating conundrum between statins and exercise also illustrates the sometimes-tenuous and evolving relationship between research and policy. Evidence-based policy attempts to cope with what is known, what is not known and what challenges remain unaddressed. Given the various levels of complexity involved when analysing the causal relationships between statins, muscle pain, exercise and how one affects the other, an option may be to limit the prescription of statins to certain groups based on different kinds of evidence (including mechanisms and raw patient data), for instance. Policymakers must therefore always aim to incorporate these facets of uncertainty into the decision-making process. Exactly how this is done effectively, however, is a subject for another blog post…

 

Words by Brendan Clarke

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