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expert reaction to study looking at death rates in hospitalised COVID-19 patients who either were or weren’t taking statins

A study, published in Cell Metabolism, has compared the death rates between hospitalised COVID-19 patients taking statins and those not taking statins.

 

Prof Jeremy Pearson, Associate Medical Director at the British Heart Foundation said:

“This study from China examined the outcome of Covid-19 infection on patients in hospital, comparing those who were treated with a statin after being admitted to hospital with those who were not.  The results indicate that those given a statin were more likely to survive after a month, despite having greater cardiovascular risk than those who were not.  The authors suggest that this is due to the anti-inflammatory actions of the statin.

“Their observations would need to be confirmed in a randomised trial, but they strengthen the view that appropriate anti-inflammatory drugs already in common use – like dexamethasone, which was recently shown to save lives in the UK RECOVERY trial – can be of real value in the treatment of patients in hospital with Covid-19.”

 

Dr Riyaz Patel, Associate Professor of Cardiology, UCL, said:

“This is a large study from China looking to see whether, among patients admitted with COVID19, statin usage is harmful or protective.  It is important to note this is not a clinical trial of statin use, instead it is an observational study where the team looked for correlations.  As such it is notoriously difficult to be sure whether statins are protective or if the findings are confounded or affected by specific biases.

“Statins are frequently given to very specific groups and this observation may be related to other unmeasured factors that could give a favourable outcome like being more wealthy or having regular access to preventative healthcare.  Some people may be too sick with cancer or other conditions and may not be given statins at all.  It is also possible those taking statins were admitted because their co-morbidities made them higher risk, while those without these comorbidities and therefore not taking statins were admitted because of more severe viral features, which would lead to an appearance that statin use was in fact protective.  The authors have tried to address some of these challenges, but such biases are very difficult to resolve.

“The study will be of interest especially as so many people take statins.  However the findings should be interpreted with significant caution and only a randomized clinical trial, such as the dexamethasone study recently, can demonstrate if treatment with statins is beneficial in the context of COVID infection.”

 

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

“This study is interesting, and the statistical analysis that led to its results is appropriate.  So why can’t it tell us that statin use causes reduced death rates in patients with COVID-19?  The main reason why not is that it’s an observational study.  People weren’t asked to take, or not take, statins by the researchers.  The statin users were people who were prescribed statins anyway, in many cases would have been taking them before they fell ill with COVID-19, and who would have been prescribed the statins because of signs and symptoms such as raised cholesterol levels.  Therefore they would be likely to differ from non-statin-users in many ways other than their statin use, and one or more of these other differences might have been the reason for the observed differences in death rates, and not the statins themselves.

“The researchers clearly understood this issue, and they make it clear in their report that their results cannot establish that statin use causes better outcomes in hospitalised COVID-19 patients, only that there is an association.  They did make appropriate statistical adjustments, in several different ways, to allow to a certain extent for the possibility that the mortality differences are caused by something else, but such adjustments can only allow for other differences on which the researchers have data.  They again make it clear that they could not allow for everything potentially relevant; in particular, because they did not have appropriate data, they were unable to adjust fully for body mass index (BMI) and could not adjust at all for the socio-economic status of the patients, both of which are known to be associated with COVID-19 mortality rates.  These and other limitations are reasons why they recommend further studies using study designs that are less affected by these limitations, such as randomized clinical trials.  I’d certainly agree with that recommendation.  And it seems that these researchers did not have full information on what medications the patients were using before they went into hospital with COVID-19.  The effect of statins in someone with COVID-19 who has not taken them before, and who may not have the usual indications for a statin prescription (such as high cholesterol levels), might possibly be very different from the effect in someone who has been using statins for some time before they became ill.  And, because a considerably higher proportion of older people in countries like the UK are already taking statins, compared to China where this research was done, the results of a similar study here might possibly look quite a bit different anyway.

“The new study provides useful evidence on the safety of certain drugs (ACE inhibitors and ARBs) in COVID-19 patients.  These drugs are quite commonly prescribed to patients with high blood pressure, and there has been speculation that they might worsen the effects of COVID-19.  This study compared people who took one of these drugs along with a statin, with statin users who did not take one of these blood pressure reducing drugs.  It found no evidence at all to suggest that ACE inhibitors or ARBs make things worse for COVID-19 patients, when taken alongside statins – indeed there was a certain amount of evidence to suggest that they might be associated with lower risks, though that evidence is not clear.  Just as with the comparison between statin users and non-users, however, it can’t be clear what is causing what here, because it is an observational study, and the number of patients involved in the ACE inhibitor and ARBs study was relatively small.  But this result, like the results of some other studies on these drugs, does provide a certain amount of reassurance that they are unlikely to be harmful in COVID-19 patients.”

 

Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“This observational study is of some interest but it is far from proving statins lower risk of COVID-19 related mortality.  The issue is that despite different types of statistical analyses, many potential confounding factors, perhaps in particular socioeconomic status, were not accounted for and could account for the findings rather than being on or off statin therapy.  In some countries, generally better educated people are more commonly on statins, and there is now ample data to show less affluent people have poorer outcomes from COVID-19.

“Also, the comment that statins are anti-inflammatory is not robust so any potential mechanisms of benefit are also unclear.

“As per normal, only randomised trials can settle this question.  If further observational studies point in same direction, then such trials should be conducted.”

 

 

‘In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19’ by Xiao-Jing Zhang et al. was published in Cell Metabolism on Thursday 25 June 2020.

DOI: 10.1016/j.cmet.2020.06.015

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30316-8

 

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

 

Declared interests

Prof Jeremy Pearson: “No conflicts of interest.”

Dr Riyaz Patel: “No relevant 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.”

Prof Naveed Sattar: “consulted for Amgen and Sanofi.”

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