December 4, 2018

expert reaction to modelling study looking at benefits and harms of statins for primary prevention

Research published in Annals of Internal Medicine suggests that statins provide net benefits at higher 10-year risks for cardiovascular disease than are reflected in most current guidelines.

Prof Kausik Ray, Professor of Public Heath, Imperial College London, said:

“The data are principally derived from modelling.  Side effects listed in package inserts are broad but absolute rates small.  Few are life threatening or permanent.  So for instance if we add GI disturbance to a rash, both of which improve with drug discontinuation and which could be more common than rare effects like myopathy, we are not comparing like for like side effects.  This will inevitably lead to the suggestion that harms outweighs benefits.  To add observational data does not help and the only way we can validate this modelling is through the CTT detailed reanalysis of a range of risk benefits in lower risk groups.  Such validation cannot come from data such as this, and taking this data alone could be potentially misleading.

“The conclusion of the editorial is apt: “Yebyo and colleagues also included a wide range of adverse events, such as hemorrhagic stroke, acute kidney injury, and hepatic dysfunction, which were largely dismissed in the ACC/AHA and USPSTF guidelines.  Accounting for this longer list of potential adverse events, which was derived from an as-yet unpublished network metaanalysis performed by the authors, inevitably tips the balance further away from net benefit and toward harm.  Is inclusion of these adverse events justified?”

“No change in clinical practice is warranted.  Discussions on risks and benefits should occur between doctor and patient so the patient is informed.  What to do should there be adverse effects and the consequences of discontinuation and of continuing therapy should be discussed.  Whilst headline grabbing, the paper by Yebyo et al does not inform the discussions any further and is considerably limited in its scope due to its methodology.”

Dr June Raine, Director of MHRA’s Vigilance and Risk Management of Medicines (VRMM) Division said:

“The benefits of statins are well established and are considered to outweigh the risk of side-effects in the majority of patients. The efficacy and safety of statins have been studied in a number of large trials which show they can lower the level of cholesterol in the blood and reduce the risk of cardiovascular disease and can save lives.

“For prevention of cardiovascular disease, statins are authorised in patients with manifest atherosclerotic cardiovascular disease or diabetes mellitus, with either normal or increased cholesterol levels, in addition to correction of other risk factors and other cardioprotective therapy.

“Trials have also shown that medically significant side effects are rare. The known side effects of statins are provided in the product information for healthcare professionals and Patient Information Leaflet which is provided with the medicine.

“Medicines safety and effectiveness is of paramount importance and under constant review. Our priority is to make sure the benefits of medication outweigh the risks. Any new significant information on the efficacy or safety of statins will be carefully reviewed and action will be taken if required.

“If you have any questions about your medicine, please speak to your GP or healthcare professional.”

‘Finding the balance between benefits and harms when using statins for primary prevention of cardiovascular disease: A modeling study’ by Henock G. Yebyo et al. was published in Annals of Internal Medicine at 22:00 UK time on Monday 3 December 2018.

Declared interests

None received.