April 3, 2016

expert reaction to a study investigating the efficacy and side-effects of cholesterol-lowering drugs in statin-intolerant patients

A comparison of a particular statin with two non-statin therapies is the subject of a paper published in the Journal of the American Medical Association.

All our previous output on this subject can be seen here.

Prof. Peter Weissberg, Medical Director at the British Heart Foundation (BHF), said:

“This carefully conducted study provides good evidence that the PCSK9 inhibitor evolocumab is effective at reducing cholesterol in patients who have experienced intolerable muscle side effects on statins and without causing muscle symptoms. Like many previous studies this one also shows that many patients who experience muscle symptoms on statins experience the same symptoms on a placebo.

“PCSK9 inhibitors are clearly very effective at reducing cholesterol but, as yet, we have no evidence that they prevent heart attacks and strokes and they are very expensive. For the time being, therefore it makes sense for their use to be restricted to those patients at greatest risk.”

Prof. Jeremy Pearson, Associate Medical Director at the British Heart Foundation (BHF), said:

“This study suggests that evolocumab could be an alternative treatment for the small minority of people with very high LDL cholesterol who do not tolerate statins. However the authors point out that, where patients had a history of reported statin intolerance, the incidence of muscle pain was not much higher when they were taking the statin than when they were taking a placebo. This shows the true incidence of muscle pain due to taking a statin is low, as reported from previous clinical trials.”

“While evolocumab is likely to be useful in patients with very high LDL cholesterol levels where statin treatment is not sufficient, it will be expensive and is delivered by home injection rather than as a pill. It is therefore not going to replace treatment for the majority of people who are lowering their risk of a heart attack or stroke by taking their statin without significant side effects.”

Prof. Liam Smeeth, Head of the Department of Non-Communicable Disease, London School of Hygiene & Tropical Medicine, said:

 “While this looks to be a robust study, I think some caution is needed in interpreting the meaning of these results for most patients. It is still far from clear whether statins really cause muscle symptoms in large numbers of patients, even though we know they can cause severe muscle problems in a very small proportion of patients. The new PCSK9 inhibitors do indeed seem effective in reducing cholesterol levels; however they’ve not been shown to protect people against cardiovascular disease, which is the only benefit of reducing cholesterol.

“In addition, PCSK9 inhibitors are hugely expensive. Given all of these factors, I don’t think their use in clinical care outside of research studies would be justified.”

‘Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance’ by Nissen et al. published in JAMA on Sunday 3rd April. 

Declared interests

Prof. Peter Weissberg: No conflicts of interest

Prof. Jeremy Pearson: No conflicts of interest

Prof. Liam Smeeth: Department receives funding from GSK. Chair of a committee of a trial for a diabetes drug made by AZ (unpaid position). Involved in an NIHR funded trial to ascertain whether statins cause muscular pain.