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expert reaction to study looking at low dose steroids and risk of cardiovascular disease

A population-based cohort study published in PLOS Medicine looks at risk of developing cardiovascular disease in patients receiving low doses of steroids.


Dr Glenis Scadding, Consultant Physician In Allergy & Rhinology at the Royal National Throat, Nose and Ear Hospital, said:

“Although present in the title, this paper fails to use the very important word ‘oral’ before ‘corticosteroid’ in the abstract.  ‘Oral’ does not mean ‘inhaled’.  It’s very important to recognise that most inhaled glucocorticosteroids – such as in asthma inhalers – contain a much lower dose that the oral one considered in this study.

“In addition, the disease studied involve systemic inflammation, which is a known cardiovascular risk factor in itself.  So it’s not clear cut that the medication was actually responsible for the increased risk of CVD.

“This is highly relevant to those using inhaled and intranasal glucocorticosteroids – which are life-saving for people with asthma, who would put themselves in much greater danger if they were to stop using them.  The inhaled dosage varies between medications, but is likely to be considerably less than the equivalent of 5mg given orally. 

“The risk/balance ratio of medications should always be considered of course, but in asthma continued use of inhaled corticosteroids is sensible, plus the occasional use of oral ones in extreme asthma cases which can prove fatal.”


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

“This research uses data from data a sample of nearly 88,000 people with six inflammatory diseases involving the immune system. It provides statistically sound evidence of an association between the amount of oral steroid drugs of a certain type (glucocorticoids such as prednisolone) that they took, and their risk of cardiovascular diseases – that is, diseases of the heart and blood circulation system, including heart attacks, strokes, some other heart diseases, and several diseases of the blood vessels.

“The study does have limitations, many of which stem from the fact that it’s observational. People weren’t allocated to particular doses of these drugs at random – they took whatever they would have taken anyway. Therefore there will have been several differences between people who took different doses of the drugs in question, or none at all. Apart from anything else, there would have been reasons why some of them were prescribed these drugs, at different dose levels, and others were not. It’s possible that the observed differences in the risk of cardiovascular diseases were caused, in part or in whole, by these other differences between the patients, rather than by the oral glucocorticoids that they might have taken. The researchers did make further statistical adjustments and analyses to investigate these other possibilities of cause and effect, and still found remaining evidence of an association between the drug dose and cardiovascular disease. But it’s impossible to be certain, from a study of this kind, exactly what the pattern of cause and effect is.

“It’s important to note that these results don’t tell us anything direct about people who take this type of steroid drug for other health conditions, because such people were not included in this study. (The drugs are sometimes used, for instance, in patients with asthma.) They also don’t tell us about steroid drugs being taken by other routes (such as inhalers) rather than swallowing them. It’s also important to note that, even of the patients with the particular inflammatory diseases that they studied, the researchers found that a great number of them were not using the drugs in question. Only 16% of them had been prescribed oral glucocorticoids in the year before the researchers started following them up. On average on each day during the follow-up period, 80% of the patients were not taking oral glucocorticoids, though this would have been an average across patients who never took them, patients who took them intermittently perhaps for short periods of time when their disease was particularly active, and patients who took them much more frequently. Some of the increases in risk, even for people taking relatively small doses of these drugs compared to people taking none at all, may sound somewhat alarming (e.g. a 74% higher risk of cardiovascular disease in people taking less than 5 mg per day, compared to people not taking the drugs at all) – but this has to be put into the context that the risks are not huge to begin with. The researchers estimated that the risk of cardiovascular disease, in people with the diseases in question who did not use these drugs at all, was 1.4% in a year, which is not particularly large given their average age (they were 58, on average, when they entered the study). So the increase in risk in people taking relatively small doses of these steroid drugs is not large in absolute terms, even if in fact it is definitely the drugs causing the increase in risk (which isn’t entirely certain).

“I’m not a medical doctor. Any treatment for any disease must balance the health gains from the treatment with any possible increases in other risks, and anyone concerned about the findings should talk to their doctors.”



‘Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study’ by M Pujades-Rodriguez et al. was published in PLOS Medicine at 7pm UK TIME on Thursday 3 December 2020.



Declared interests

Dr Scadding:

  • Honoraria for articles, speaker  and advisory boards:
    ALK,  Astra Zeneca, Brittania Pharmaceuticals, Capnia, Church & Dwight,  Circassia, Groupo Uriach, GSK, Meda/Mylan, Merck, MSD, Ono Pharmaceuticals, Oxford Therapeutics, Sanofi-Aventis ,Stallergenes,UCB 
  • Travel funding: ALK, Bayer, GSK, Meda 
  • Lead for BSACI Rhinitis guidelines 
  • Past Chair of EAACI Ethics Committee 
  • Scientific Chief Editor,  Rhinology Section, Frontiers in Allergy 
  • Lead for Allergic Rhinitis, EUFOREA 
  • Chair of Data Monitoring Board for Paediatric AR trials of HDM SLIT 

Prof McConway: “I am a Trustee of the SMC and a member of the Advisory Committee, but my quote above is in my capacity as a professional statistician

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