Effects of statins on muscle pain assessed

By Nicole MacKee
Statins have no effect on moderate muscle symptoms, such as pain and weakness, UK researchers have reported in The BMJ, but a leading Australian lipidologist has suggested the study conclusion may be ‘flawed’.

The researchers said that a causal link between statins and rare, but severe, muscle adverse effects was well established, but uncertainty remained about a link between the drugs and less severe symptoms, such as stiffness, pain and weakness.

To investigate a possible link, the researchers conducted a series of n-of-1 trials with 200 participants who had recently stopped, or were considering stopping, statin treatment because of muscle symptoms. In the StatinWISE trial, participants were randomised to a series of six double-blind treatment periods (of two months each), where they took either atorvastatin 20 mg daily or placebo.

After 12 months, the researchers found no overall difference in muscle symptom scores reported during the statin and placebo periods. And, they reported, two-thirds of participants who completed the trial (74 out of 113, 66%) had already resumed, or were planning to resume, statin treatment.

Leon Simons, Associate Professor of Medicine and Director of the Lipid Research Department at UNSW, Sydney, said he suspected that the overall study conclusion was potentially flawed, and the findings were unlikely to be generalisable to all patients.

‘We are not told what proportion of pre-identified patients failed to accept the invitation to participate, or what proportion were excluded by virtue of important and justified exclusion criteria,’ Professor Simons said.

Also, he noted, 43% of subjects did not complete the full study, suggesting that a serious population bias may have influenced the findings. The researchers reported that two participants died, four were lost to follow up and 80 out of 200 withdrew.

Professor Simons said The BMJ paper was also dismissive of a 2016 Journal of the American Medical Association study that highlighted the complex relation between statins and muscle problems (JAMA 2016; 315: 1580-90).

In the JAMA study, he said, 491 patients previously reporting myalgia were challenged with atorvastatin 20 mg or placebo in a double-blind crossover study.

‘Forty-three per cent experienced symptoms while using atorvastatin but not with placebo; 27% did so with placebo but not with atorvastatin; 10% did so on both, while 17% had no symptoms at all,’ Professor Simons noted.

Concern about muscle symptoms deterred many patients from commencing or continuing statin therapy to reduce their cardiovascular disease (CVD) risk, he said.

‘While some instances of myalgia may not be causally related to statin therapy, the situation is very complex and careful ongoing management is required to reduce CVD risk,’ he said. ‘This might be through a switch to another statin at low dose, less frequent administration of low dose statin, or the use of non-statin therapy.’
BMJ 2021; 372: n135 http://dx.doi.org/10.1136/bmj.n135.