October 16, 2019

expert reaction to benefits of statins for low risk patients

A study, published in The BMJ, reports that the benefits of statins for patients without heart disease may be small and uncertain.

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said:

“This article draws on the authors’ own three previous papers, namely two observational analyses from The Irish Longitudinal Study on Ageing and an overview of systematic reviews by other investigators. The conclusions are not surprising and align with what we know already, based on the evidence from numerous independent clinical trials.

“The evidence from clinical trials going back more than two decades shows that statins are an effective way of people reducing their risk of a heart attack. We already know that the benefits are even greater for people who have already had a heart attack or stroke. An important area of debate here relates to the magnitude of benefit provided by statin treatment in people who are at relatively low risk and whether that benefit outweighs the risk of side effects. For people who fall into this category, the decision on whether to take statins should be based on discussion with their GPs.

“We recognise people’s concerns about statin side effects and we want patients and their doctors to be able to make informed, evidence-based decisions about taking and prescribing these medicines. The BHF is doing its bit by funding researchers to gather, analyse, and make available all the individual participant data from large clinical trials into statins. Putting an end to this debate should help to stop conflicting reports, which can put people off taking potentially life-saving drugs that they have been prescribed for good reason.”

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

“It’s important to understand that this paper isn’t providing any new evidence. Instead it is putting forward the authors’ interpretation of the implications of previous work, much of it done by the same authors, and much of which is in turn based on reviews of evidence from other researchers. That’s a useful exercise, in my view, because this subject is complicated and contested. The subject is the use of statins for primary prevention of cardiovascular disease (CVD; that is, heart attacks, strokes and so on), that is, prescription of statins to people who have not (yet) had CVD, with the aim of making it less likely that they will have such a disease in future.

“Really, the authors’ conclusion is that we don’t know enough about how much the risk of disease is reduced by taking statins, in several specific groups and types of patients. That might sound a little surprising, given the amount of research that there has been on statin use. But the authors point out that quite a lot of the previous work has essentially estimated average reductions in risk, averaged over groups with a range of characteristics – different age groups, differences in other factors affecting their CVD risk, and so on. An individual patient contemplating taking statins isn’t ever an exactly average person – no such thing exists. So it would be good if the patient had a better estimate of how much their own risk would be reduced. That’s impossible to estimate for a single individual, and even estimating it for a limited group of people that are similar to the individual patient is difficult. That requires studies that have substantial numbers of participants in each of the relevant age groups and risk groups separately.

“In some previous studies, there is already a certain amount of data for such small groups, and it does not always show a statistically significant risk reduction from statins. It’s important to understand that that does not mean that statins have no effect for these people, because the lack of statistical significance can also mean that not enough of them were studied to estimate the risk reduction adequately. So we still don’t know whether there’s a real reduction or not. If there is a risk reduction, it’s likely to be small for people who have a low CVD risk, but we don’t have a very good handle on exactly how small. The authors, I believe, aren’t saying that statins are inappropriate for certain groups – instead they are saying that the reductions in CVD risk from taking statins are likely to be small for people at low CVD risk, so it’s important to find out more about the size of those reductions and also about the likelihood of any harmful effects. Then clearer guidelines and more appropriate decisions on prescribing could be made, that also take into account the patient’s own view of the balance between benefits and risks.

“It’s true that the authors wrote that, in the specific context of the use of statins in patients at low risk of CVD, they ‘may be an example of low value care … in these patients and, in some cases, represent a waste of healthcare resources’. (My emphases.) However, the word ‘may’ is important here, and the sentence is referring to patients with low CVD risk. The following sentence in the paper points out that it’s very difficult to decide what is appropriate use of statins and what may be overuse or low value care, because the necessary information is not available (and, in relation to single individual patients and their preferences, it never will be perfectly available). So the paper is decidedly not arguing that prescribing statins is definitely wrong for people at low CVD risk. It is pleading for more and larger clinical trials and better data on both harms and benefits, so that decisions can be based on better information.”

* ‘Statins for primary prevention of cardiovascular disease’ by Byrne et al. was published in The BMJ at 23:30 UK time on Wednesday 16th October 2019. 

DOI: 10.1136/bmj.l5674

Declared interests

Prof Metin Avkiran: No Conflicts

Prof Kevin McConway: Prof McConway is a member of the SMC Advisory Committee, but his quote above is in his capacity as a professional statistician.